1.
A 56-year-old male comes to see an Oncologist to discuss adjuvant chemotherapy for his recently diagnosed T3 N0 Colon cancer that has been surgically removed. The tumor originated in his left colon. His Surgical Oncologist performed the surgery.
On his pathology report, he is found to be a T3 N0 adenocarcinoma. The surgical margins are negative. It is a low-grade tumor, there is no evidence of LVI or PNI and all 14 lymph nodes that are removed are negative for cancer involvement. Further tumor analysis reveals that the cancer is MSI-H. The patient will be meeting with a Genetic counselor. Given that the tumor is MSI-High, what does it tell one regarding the efficacy of adjuvant therapy for this patient ?
A . He will benefit from receiving Bevacizumab
B . He will benefit from receiving just 5-FU
C . He will benefit from receiving FOLFOX
D . He will not benefit from 5-FU therapy
E . He will not benefit from Bevacizumab
Your Answer : Option
Not Answered
Correct Answer : Option
D
Explanation:D) He will not benefit from 5-FU therapy
The benefit of adjuvant chemotherapy for patients with Stage II Colon cancer is somewhat marginal. The NCCN panel believes that it is reasonable to accept the relative benefit of adjuvant therapy in Stage III disease as indirect evidence of benefit for Stage II disease, especially for those patients who present with high-risk features.
The QUASAR trial demonstrated a small benefit in the Overall survival in patients with Stage II disease who were treated with 5-FU/LV compared to patients not receiving adjuvant therapy (RR of recurrence at 2 years, 0.71; P=.01). In this trial though, 64% of patients had fever than 12 lymph nodes sampled. So, it may have been that these patients had higher risk disease due to undergoing suboptimal surgery and therefore this is the reason they benefited from adjuvant therapy.
Colon cancer patients who present with Stage II disease that is high for microsatellite instability (MSI-H) or who have defective DNA mismatch repair have a good prognosis and do not benefit from receipt of adjuvant 5-FU chemotherapy.
A group of investigators examined MMR status as a predictor of adjuvant therapy benefit in patients with stage II and III colon cancer.
MSI assay or immunohistochemistry for MMR proteins were performed on 457 patients who were previously randomly assigned to FU-based therapy (either FU + levamisole or FU + leucovorin; n = 229) versus no postsurgical treatment (n = 228). Data were subsequently pooled with data from a previous analysis. The primary end point was disease-free survival (DFS).
Overall, 70 (15%) of 457 patients exhibited dMMR. Adjuvant therapy significantly improved DFS (HR=0.67; P = .02) in patients with pMMR tumors. Patients with dMMR tumors receiving FU had no improvement in DFS (HR, 1.10; P = .85) compared with those randomly assigned to surgery alone. In the pooled data set of 1,027 patients (n = 165 with dMMR), these findings were maintained; in patients with stage II disease and with dMMR tumors, treatment was associated with reduced overall survival (HR, 2.95; P = .04).
In the NCCN guidelines, patients with T1-T4, N0, M0 colon cancer that is MSI-High/MMR deficient should undergo observation after surgical extirpation of the tumor.
**Pearl:
At this point in time, no molecular marker should be used in guiding treatment decisions in the adjuvant setting for patients with stage III colon cancers. The MSI-H/ MMR-D phenotype is only associated with excellent prognosis in stage II and not as much in stage III/IV cancers.
**Pearl: 15% of sporadic tumors are MSI
**Pearl: MSI-H tumors are often right-sided, have undifferentiated histology, oftentimes present as stage II and
is often seen in female patients
**Pearl: Poorly differentiated histology is not considered a high-risk feature for patients with Stage II disease
whose tumors are MSI-High
Reference: Sargent DJ et al. Defective mismatch repair as a predictive marker for lack of efficacy of fluorouracil-based adjuvant therapy in colon cancer. J Clin Oncol 2010; 28(20): 3219-26
2.
A 19-year-old male was recently diagnosed with Good risk, Stage IIB (S1) NSGCT. Four weeks ago, he underwent an orchiectomy for a suspicious indurated mass located on his right testicle. Pathology revealed that he had a nonseminoma. He was referred over to see Medical Oncology for further evaluation.
A CXR is ordered and is negative. CT Abdomen/Pelvis with IV contrast shows a 4 cm mass in the retroperitoneum. Post-orchiectomy tumor markers are sent. LDH and beta-hCG are both normal. The AFP is 145 ng/ml. This is repeated 1 week later and it has increased to 175 ng/ml. The patient undergoes sperm banking. PFTs are performed and are within normal limits.
He started his first cycle of BEP. Bleomycin is being given at 30 units weekly. Three days after finishing his 1st cycle of therapy (Day 1, 8, 15 of bleomycin, and days 1-5 of etoposide and cisplatin), he develops dyspnea and a dry cough.
Chest imaging is ordered and confirms pneumonitis. This is from exposure to Bleomycin. He partially recovers from this episode and comes to see his Medical Oncologist to discuss starting his second cycle of therapy. The original plan was to administer BEP x 3 cycles. What should be recommended?
A . Give bleomycin at full dose
B . Give bleomycin at a 25% dose reduction
C . Give bleomycin at a 50% dose reduction
D . Do not give bleomycin. Substitute ifosfamide instead
E . Give EP alone for 3 more cycles
Your Answer : Option
Not Answered
Correct Answer : Option
E
Explanation:E) Give EP alone for 3 more cycles
Patients with Stage IIB, S1 NSGCT should be offered either BEP x 3 cycles or EP x 4 cycles.
As he has developed bleomycin lung toxicity, one should not risk offering him more treatment with Bleomycin. One would not want him to develop pulmonary fibrosis which can be fatal. EP x 4 is a perfectly acceptable treatment regimen for him. As he has completed 1 cycle of BEP already (with contains EP), one can give him 3 more cycles of EP and then stop therapy.
Bleomycin pulmonary toxicity can often start off as pneumonitis but can eventually progress to the development of fibrosis. The incidence of bleomycin-induced pulmonary fibrosis can be as high as 10%. After stopping the drug, one can administer high-dose steroids to help the treat the inflammation.
**Pearl:
If a patient has Intermediate risk or Poor risk Nonseminoma, one can substitute Ifosfamide for Bleomycin. This is known as the VIP regimen. It is mostly offered to patients who have a contraindication to receive Bleomycin.
Reference: Maher J, Daly PA. Severe bleomycin lung toxicity: reversal with high dose corticosteroids. Thorax 1993; 48(1): 92-94
3.
A 72-year-old male has recently started palliative chemotherapy with Gemcitabine + Nab-Paclitaxel for his Stage IV Pancreatic cancer. Three months ago, he was diagnosed with metastatic pancreatic cancer. Baseline imaging revealed the presence of several liver metastases. A biopsy of a liver lesion was performed with Pathology confirming the diagnosis. Next generation sequencing of the tumor revealed no targetable lesions including no mutation in BRCA1 or BRCA2.
He is started on treatment with Gemcitabine + Nab-Paclitaxel and has completed 3 cycles of treatment. A restaging CT Abdomen/Pelvis with IV contrast shows that he has had a partial response with a 60% reduction of his liver lesions. He has tolerated therapy very well thus far.
The patient acutely develops marked fatigue and light-headedness. He is brought to the local ER by his family. A workup demonstrates that he has acute renal failure. Labs reveal a Hemoglobin of 7.4 g/dl and the platelet count is 72,000 per mL. His Creatining is 3.2 mg/dl and the PT and PTT are both normal. The Hematologist Oncologist on call is consulted. A blood smear is reviewed and shows lots of schistocytes. What is the most likely etiology for this patient’s acute clinical worsening?
A . DIC from Pancreatic cancer
B . HUS from Gemcitabine
C . Trousseau's Syndrome
D . ATN from Nab-Paclitaxel
E . Stauffer’s syndrome
Your Answer : Option
Not Answered
Correct Answer : Option
B
Explanation:B) HUS from Gemcitabine
Gemcitabine is a Pyrimidine analog. It is metabolized within cells to the active nucleoside forms: diphosphate and triphosphate. Gemcitabine diphosphate inhibits ribonucleotide reductase. Gemcitabine triphosphate competes to be incorporated into DNA. In doing so, DNA synthesis is halted.
Hemolytic uremic syndrome (HUS) is a rare thrombotic condition that is characterized by a triad of microangiopathic hemolytic anemia, thrombocytopenia and acute renal failure.
In this condition, a patient will oftentimes be found to have an elevated LDH, low haptoglobin and schistocytes on the peripheral blood smear. A renal biopsy would show microvascular damage of the arterioles and small arteries occluded by eosinophilic hyaline thrombi containing fibrin and platelet aggregate.
Several etiologies that can cause this condition include cancers, chemotherapy drugs and infections.
The mechanism of gemcitabine-induced HUS is unclear. Some posit that this chemotherapy medication may lead to microvascular endothelial damage or immunocomplex deposition.
There is no consensus as to the best treatment for Gemcitabine related HUS.
However, one should immediately discontinue gemcitabine if HUS is seen. Other potential therapies include steroids, FFP administration, plasmapheresis or hemodialysis. It is unclear how well these therapies work.
**Pearl: Mitomycin C can also cause HUS
Reference: Muller S. Hemolytic uremic syndrome following prolonged gemcitabine therapy: report of four cases from a single institution. Ann Hematol 2005;84(2): 110-4.
4.
A 62-year-old female is s/p TAH/BSO, comprehensive surgical staging and optimal debulking for a recently diagnosed left-sided ovarian cancer. Final pathology reveals a Carcinosarcoma/Malignant Mixed Mullerian tumor. She is found to have stage II disease. She was optimally debulking with all sites of disease being surgically removed.
Prior to her undergoing surgery, she had a CT C/A/P that revealed no signs of metastatic disease.
Her CA-125 is 12 U/ml. BRCA 1 and 2 are wild-type on both germline and somatic testing. The tumor is HRD-.
She is in very good health with no comorbid medical conditions. What should be offered as adjuvant therapy?
A . Observation
B . IP Cisplatin and IP/IV Paclitaxel chemotherapy
C . Adjuvant chemotherapy with Adriamycin + Ifosfamide x 6 cycles
D . Adjuvant Gemcitabine + Docetaxel x 6 cycles
E . Adjuvant Carboplatin + Paclitaxel x 6 cycles
Your Answer : Option
Not Answered
Correct Answer : Option
E
Explanation:E) Adjuvant Carboplatin + Paclitaxel x 6 cycles
Carcinosarcomas consists of malignant epithelial and mesenchymal components. They account for < 2% of
all malignant Ovarian cancers. These are rare tumors that carry a poor prognosis.
Many pathologists consider these tumors to be a variant of poorly differentiated epithelial ovarian cancer
[metaplastic carcinoma].
Patients with carcinosarcomas are not candidates for fertility-sparing surgery regardless of the age
or stage of disease. Optimal surgical debulking is recommended for patients who present with this type of
Ovarian cancer.
Patients with carcinosarcomas should be treated with adjuvant Carboplatin/Taxol. This is the
preferred adjuvant chemotherapy option. Bevacizumab can also be given as part of the adjuvant treatment.
Ovarian Carcinosarcoma:
Stage I-IV: Patients should be offered chemotherapy with Carboplatin + Taxol
One can substitute Docetaxel or Liposomal Doxorubicin for Taxol
Essentially, patients with Ovarian carcinosarcomas and High-Grade Serous malignancies are treated similarly.
However, for a patient with a Stage I Ovarian Carcinosarcoma, one could consider 3-6 cycles of adjuvant
Carboplatin/Taxol. Patients with Stage I High-grade Serous Ovarian cancer should receive 6 cycle of
chemotherapy.
Although not preferred, the following are the other adjuvant chemotherapy options that can be offered to patients
who have Ovarian Carcinosarcoma:
--Carboplatin + Ifosfamide
--Cisplatin + Ifosfamide
--Paclitaxel + Ifosfamide
Reference: Leiser AL et al. Carcinosarcoma of the ovary treated with platinum and taxane: the memorial Sloan-Kettering Cancer Center experience. Gynecol Oncol 2007;105(3):657-61
5.
A 59-year-old female has recently undergone a maximal complete resection of a brain tumor located at his left parietal lobe. Neurosurgery performed the surgery and was able to remove all the tumor.
Final pathology reveals a WHO Grade 3 Oligodendroglioma. Further analysis of the tumor specimen reveals codeletion of 1p9q. An IDH1 mutation is seen. A Brain MRI that is performed two days after surgery confirms that all the tumor has been surgically removed. Her Karnofsky performance status is >90. What adjuvant therapy should be offered?
A . Standard Radiation
B . Standard Radiation with BCNU wafer
C . Chemotherapy with Temozolamide
D . Standard Radiation therapy and neoadjuvant or adjuvant Lomustine, Procarbazine, and Vincristine (PCV) chemotherapy
E . Observation
Your Answer : Option
Not Answered
Correct Answer : Option
D
Explanation:D) Standard Radiation therapy and neoadjuvant or adjuvant Lomustine, Procarbazine,
and Vincristine (PCV) chemotherapy
Anaplastic oligodendrogliomas are chemotherapy-sensitive tumors. A phase III study (EORTC 26951) evaluated the benefit of adding adjuvant PCV x 6 cycles with RT vs. RT alone (59.4 Gy) to this cohort of patients. A total of 368 patients were enrolled. The overall survival favored the RT/PCV group (42.3 vs. 30.6 mo; HR=0.75).
In the 80 patients whose Glioma harbored a 1p/19q codeletion, the overall survival favored PCV arm (Not reached vs. 112 mo; HR=0.56) . IDH mutational status was also of prognostic significance.
Gliomas that harbored the 1p/19q codeletion had a better prognosis.
RTOG 9402 randomized 291 patients with anaplastic oligodendroglioma or anaplastic oligoastrocytoma to receive either PCV followed by immediate RT or RT alone. No difference in the median Overall survival was seen between either arm (4.6 years vs. 4.7 years; P=0.10). However, an unplanned subgroup analysis of the 126 patients whose tumors were 1p19q co-deleted found a doubling in the median Overall survival (14.7 vs. 7.3 years; HR=0.59; P=0.03) when PCV was added to RT as upfront treatment.
The NCCN panel recommends that PCV be administered after RT (as per EORTC 26951) since the intensive PCV regimen given prior to RT (RTOG 9402) was not tolerated as well.
The phase III CODEL study was designed to assess the efficacy of Temozolomide for the treatment of newly diagnosed anaplastic [Grade III] Oligodendrogliomas. The study was redesigned to compare RT + PCV to RT + Temozolomide in patients with anaplastic oligodendroglioma as well as low-grade oligodendroglioma. Results of this important study are pending.
Of note, the 2016 WHO classification of tumors of the CNS has deleted oligoastrocytoma as a category.
https://www.nccn.org/professionals/physician_gls/pdf/cns.pdf
Reference: Van den Bent MJ, et al. Adjuvant procarbazine, lomustine, and vincristine chemotherapy in newly diagnosed anaplastic oligodendroglioma: long-term follow-up of EORTC brain tumor group study 26951 J Clin Oncol 2013;31(3):344-50
6.
A 48-year-old male who is a 40-pack-year smoker but quit 10 years ago, has recently been diagnosed with limited-stage Small cell lung cancer.
A baseline PET-CT shows an avid left-sided lung mass that measures 6 cm in size. No other concerning sites of disease are seen. A biopsy of this mass confirms Small cell lung cancer. A Brain MRI is negative. A CBC with Plt/Diff and CMP are within normal limits. The patient is healthy and has an ECOG PS=1.
What treatment should be offered to this patient?
A . Lobectomy followed by adjuvant Carboplatin/Paclitaxel
B . Concurrent chemoradiation with Carboplatin/Etoposide. Radiation to be given in daily fractions for a total dose of 66 Gy. Consider PCI after completion of concurrent chemoradiation
C . Concurrent chemoradiation with Cisplatin/Etoposide. Radiation to be given in bid fractions for a total dose of 45 Gy. Consider PCI after completion of concurrent chemoradiation
D . Give Cisplatin/Etoposide x 4 cycles followed sequentially by Radiation therapy in daily fractions to a dose of 66 Gy. No PCI needed as a baseline brain MRI is negative
E . None
Your Answer : Option
Not Answered
Correct Answer : Option
C
Explanation:C) Concurrent chemoradiation with Cisplatin/Etoposide. Radiation to be given in bid fractions for a total dose of
45 Gy. Consider PCI after completion of concurrent chemoradiation
Cisplatin/Etoposide is the preferred systemic chemotherapy to give (not Carboplatin/Etoposide) when offering concurrent chemoradiation to patients who present with limited stage Small cell lung cancer.
For patients who present with Extensive stage disease, one can offer either Carboplatin or Cisplatin. This is an important distinction.
A seminal study (see the reference below) demonstrated that twice a day (hyperfractionated) radiation confers a survival benefit over daily radiation when treating patients with limited stage Small cell lung cancer.
--45 Gy in 3 weeks (1.5 Gy bid) > 45 Gy in 5 weeks (1.8 Gy daily)
--5-year OS 26% with bid XRT vs. 16% for daily RT (P=0.04)
However, these radiation doses were not biologically equivalent so this created some measure of controversy.
When BID fractionation is used, a total of 45 Gy is normally given and there should be at least a 6-hour interfraction interval to allow for repair of normal tissue. If one is using once-daily RT, higher doses of 60-70 Gy should be used.
Two randomized phase III trials did not demonstrate superiority of 66 Gy in 6.5 weeks/2 Gy daily (The European CONVERT trial) or 70 Gy/2 Gy daily (CALGB 30610/RTOG 0538) over 45 Gy in 3 weeks/1.5 Gy BID, but overall survival and toxicity were similar.
Recent randomized phase II trials suggest that higher dose accelerated RT of 60-65 Gy in 4-5 weeks given in BID or daily fractionation may produce increased overall or PFS compared to 45 Gy in 3 weeks in BID fractionation.
As mentioned above, the randomized, phase III European CONVERT trial did not demonstrate superiority of 66 Gy (once daily) over 45 Gy (BID), but overall survival and toxicity were comparable.
https://www.nccn.org/professionals/physician_gls/pdf/sclc.pdf
Corinne Faivre-Finn et al. Concurrent once-daily versus twice-daily chemoradiotherapy in patients with limited-stage small-cell lung cancer (CONVERT): an open-label, phase 3, randomised, superiority trial. Lancet Oncology 2017.
Reference: Turrisi AT et al. Twice-daily compared with once-daily thoracic radiotherapy in limited small-cell lung cancer treated concurrently with cisplatin and etoposide. N Engl J Med 1999;340(4):265-71
7.
A 52-year-old female is undergoing treatment for her stage IV melanoma. She was diagnosed with Stage IV disease over 1 year ago. A baseline PET-CT revealed both lung and liver lesions. The index liver lesion measures 3 cm in size. Interventional Radiology performed a biopsy of this liver lesion. Pathology revealed a BRAF Wild-type Melanoma. NGS testing reveals no other mutations. A baseline brain MRI was negative.
She was initially started on Nivolumab as frontline therapy. Restaging studies revealed a partial response. However, after 1 year of treatment she developed progression of her disease.
A recent restaging CT scan shows that the liver lesion measures 4.5 cm in size. She has also had developed two new lung lesions. She is started on Ipilimumab 3 mg/kg and she had had 2 cycles of treatment. Thus far, she has tolerated treatment well outside of having Grade 1 diarrhea that is well controlled with Immodium.
She just presented to a local ED for some bloating. A full workup is performed and is negative. Her CMP, Amylase, Lipase and Abdominal X-ray are all negative. She has a CT scan with IV contrast performed and it that reveals that all the lesions are stable except that her index liver lesion has increased in size from 4.5 to 5 cm over the span of 3 weeks. What should be recommended?
A . Stop Ipilimumab and switch to Pembrolizumab + Ipilimumab
B . Increase the dose of Ipilimumab to 10 mg/kg
C . Continue therapy
D . Switch therapy to Nivolumab + RelatlimabÂ
E . Switch therapy to Lifileucel
Your Answer : Option
Not Answered
Correct Answer : Option
C
Explanation:C) Continue therapy
The patient in this question has just started on immunotherapy with Ipilimumab. It would be premature to assume that the slight enlargement of her liver lesion represents true tumor progression. This patient should be continued on therapy. Responses to immunotherapy can sometimes be delayed.
It can take time before once sees a cancer respond to immunotherapy. One needs to be careful with stopping therapy too soon based on an interval CT imaging especially if it was performed for a possible non-oncologic reason.
Sometimes, responses can occur even after the initial appearance of radiologic evidence of disease progression. Pseudo-progression refers to cancer deposits that initially appear larger on a scan, perhaps due to the infiltration of the immune cells to the tumor location. However, these areas will likely regress with time. The patient had a CT scan performed to evaluate her issues with bloating. It was not a definitive restaging scan. Additionally, this CT scan took place after she received only 2 doses of Ipilimumab.
Ipilimumab is a humanized monoclonal IgG1 antibody that targets Cytotoxic T-lymphocyte antigen-4 (CTLA-4). CTLA-4 on T cells acts as a break for the normal immune system. By blocking CTLA-4, Ipilimumab unleashes the immune system leading to T-cell activation.
This drug attained FDA approval in 2011 as monotherapy (3 mg/kg) x 4 cycles for patients with unresectable or metastatic melanoma (both pre-treated or chemotherapy naïve patients).
Of note, most would have offered this patient combination immune checkpoint inhibitor therapy in the frontline setting.
Reference: Graziani G et al. Ipilimumab: a novel immunostimulatory monoclonal antibody for the treatment of cancer. Pharmacol Res 2012;65(1):9-22.
8.
A 56-year-old female presents to see her Medical Oncologist to discuss further treatment options for her Dermatofibrosarcoma protuberans (DFSP).
Two years ago, she presented to see her Primary Care Physician for evaluation of a large macular lesion that was located on her right upper back that had been progressively growing. She was referred over to see a Dermatologist who performed a biopsy of this lesion. Pathology revealed a DFSP. The tumor was CD34+.
The patient was referred over to see a Surgical Oncologist who excised the tumor with Mohs surgery. The surgical margins are negative. No adjuvant therapy is given.
She has been undergoing close surveillance with her Oncology team. A recent surveillance CT scan revealed 12 lesions located in the lungs. A biopsy of a lung lesion was performing with Pathology confirming DFSP. Further testing of the Sarcoma reveals t(17;22). Which therapy should be offered?
A . Hospice
B . Imatinib
C . Cisplatin + Etoposide
D . Carboplatin + Paclitaxel
E . Pembrolizumab
Your Answer : Option
Not Answered
Correct Answer : Option
B
Explanation:B) Imatinib
Dermatofibrosarcoma protuberans (DFSP) is a tumor that occurs in the dermis layer of the skin.
Up to 5% of these tumors can metastasize. These tumors can initially appear as a bruise or pimple. Over 90% are slow growing tumors. A subset of DFSP can harbor a high-grade sarcomatous component.
The majority (> 90%) of these tumors will harbor t(17;22). This translocation fuses the collagen gene (COL1A1) with the platelet-derived growth factor (PDGF) gene. This results in a fusion protein that leads to a potent growth factor (PDGFRB).
The primary treatment for patients who present with localized disease is surgery to achieve negative margins. Surgical approaches include:
Excision with other forms of peripheral and deep en face margin assessment [PDEMA]
Mohs Micrographic surgery
Phase II data that evaluated the efficacy of Imatinib in the treatment of patients with locally advanced or metastatic DFSP revealed an objective response rate of almost 50%. The median time to progression was 1.7 years.
Imatinib is approved by the FDA for the treatment of unresectable, recurrent, and/or metastatic DFSP in adult patients.
Of note, patients with unresectable (but locoregional) DFSP can be offered neoadjuvant imatinib in hopes of downstaging the tumor to enable resection.
Reference: Rutkowski P et al. Imatinib mesylate in advanced dermatofibrosarcoma protuberans: pooled analysis of two phase II clinical trials. J Clin Oncol 2010;28(10):1772-9.
9.
A 48-year-old female presents to see her PCP for evaluation of a left-sided neck mass that has been getting progressively larger in size over the past 6 months. She is in overall good health and has no known medical conditions. Her Primary care physician performs a thorough workup and orders a neck ultrasound that reveals a 2 cm left cervical lymph node that appears concerning for malignancy.
The patient is set up for an incisional biopsy with Interventional Radiology. Pathology confirms classic (grade I) follicular lymphoma. She is referred over to see an Oncologist who performs a bone marrow aspirate and biopsy. Pathology confirms that there is no lymphoma involvement. A PET-CT scan shows only FDG activity at this solitary left-sided neck lymph node. She is felt to have stage I disease. The LDH, CMP and CBC with Platelet/Differential are all normal. What should be offered as therapy?
A . Observation
B . R-CHOP
C . R-CVP
D . Radiation therapy [ISRT]
E . Lenalidomide and Rituximab
Your Answer : Option
Not Answered
Correct Answer : Option
D
Explanation:D) Radiation therapy [ISRT]
Follicular lymphoma usually does not present in a localized manner. However, in instances where the Follicular lymphoma is localized (ie, Stage I or contiguous Stage II), then one should consider treating with ISRT/Radiation. Studies have shown that this modality of treatment for early stage Follicular Lymphoma can lead to a long-term remission.
Observation, single agent Rituximab, Rituximab/Lenalidomide or Rituximab (or Obinutuzumab) + chemotherapy are the systemic treatment options to offer patients with Follicular lymphoma. However, these are perhaps best served as treatment options for patients with more advanced Follicular lymphoma.
On study retrospectively evaluated the effectiveness of radiation in 177 patients with stage I or II follicular small cleaved-cell and follicular mixed small cleaved-cell and large-cell non-Hodgkin's lymphoma.
Radiotherapy doses ranged from 35 to 50 Gy. The median survival time was 13.8 years. At 20 years, 37% patients were relapse-free. Only five of 47 patients who reached 10 years without relapse subsequently developed recurrence.
The NCCN guidelines listed ISRT as the preferred therapy for patients with Stage I or contiguous Stage II, Classic Follicular lymphoma.
Reference: Mac Manus MP, Hoppe RT. Is radiotherapy curative for stage I and II low-grade follicular lymphoma? Results of a long-term follow-up study of patients treated at Stanford University. J Clin Oncol 1996;14(4):1282-90.
10.
A 59-year-old female with Chronic Phase CML has been on Imatinib 400 mg daily for 18 months. Baseline evaluation revealed low-risk disease on the Hasford Euro scoring system. During her 3-month, 6-month and 12-month evaluation, she was found to be in MMR. Outside of some periorbital edema, she has tolerated therapy well.
During her 18-month evaluation, the Bcr-Abl transcript has increased to 12% and FISH testing showed the presence of t(9;22). A bone marrow biopsy is performed and she was found to be in cytogenetic relapse. Three of 20 metaphases harbor Ph+. She has been compliant with imatinib and has not been on any other medications. Mutational analysis of the BCR-ABL kinase domain reveals F317L. What should be recommended?
A . Increase Imatinib to 800 mg daily
B . Offer an immediate Allogeneic SCT
C . Continue therapy, but recheck a bone marrow biopsy with cytogenetics in 3 months
D . Continue therapy, but add Interferon to Imatinib
E . Switch to a different TKI
Your Answer : Option
Not Answered
Correct Answer : Option
E
Explanation:E) Switch to a different TKI
This patient has relapsed disease. This is defined by any of the following:
--Any sign of loss of Hematologic response
--Any sign of loss of CCyR or its molecular response correlate (MR2.0: BCR::ABL1≤1%) defined as an increase
in BCR-ABL1 transcript to >1%
--1-log increase in BCR-ABL1 transcript levels with loss of MMR
At the 18-month follow-up mark, to see a cytogenetic relapse is disconcerting. According to the NCCN guidelines, having a BRC-ABL1 > 10% at the 3-month mark connotes TKI resistance.
In situations like this, one needs to check for patient compliance to the TKI and other drug-drug interactions. Prior to switching therapy for a presumed TKI failure, one should also check the mutational status of BCR-ABL. For second-line treatment for patients with TKI-resistant disease, one should switch to another alternate TKI that is tailored to the results of the BCR-ABL1 mutation testing. These patients should also be evaluated for an allogeneic HCT.
There is a subset of BCR-ABL mutant clones associated with impaired responses to second-generation TKIs.
As an example, for patients who harbor a F317L mutation in BCR-ABL1, one would offer Nilotinib over Dasatinib or Bosutinib. If a patient has a G250E mutation, one would offer Dasatinib or possibly Nilotinib.
The following are the contraindicated mutations for each TKI:
Asciminib: A337T, P465S or F359V/I/C
Bosutinib: T315I, V299L, G250E, F317L
Dasatinib: T315I, T315A, F317 L/V/I/C, V299L
Nilotinib: T315I, Y253H, E255 K/V, F359 V/C/I
Ponatinib: No contraindicated mutations
Mutations contraindicated for imatinib are numerous.
Bosutinib has minimal activity against F317L mutation.
https://www.nccn.org/professionals/physician_gls/pdf/cml.pdf
Reference: Jabbour E et al. Practical advice for determining the role of BCR-ABL mutations in guiding tyrosine kinase inhibitor therapy in patients with chronic myeloid leukemia. Cancer 2011;117(9):1800-11
11.
A 42-year-old female was recently diagnosed with stage II Right-sided breast cancer. On a routine screening mammogram, she was found to have a 3 cm right breast mass. There is no radiologic signs of her having pathologic axillary lymphadenopathy. The patient is referred over to a Comprehensive Breast center. Genetic testing reveals that she harbors a BRCA1 mutation.
The patient undergoes a biopsy of this 3 cm mass. Pathology confirms that she has breast cancer. Which of the following is the most likely type of breast cancer that this patient has?
A . ER+, PR+, Her2-
B . ER+, PR-, Her2-
C . ER+, PR+, Her2+
D . ER-, PR-, Her2-
E . ER-, PR-, Her2+
Your Answer : Option
Not Answered
Correct Answer : Option
D
Explanation:D) ER-, PR-, Her2-
Hereditary Breast Ovarian cancer syndromes are autosomal dominant disorders. BRCA1 and BRCA2 are tumor suppressor genes whose role is to control cell growth and cell death. Mutations in these genes disenable this function leading to an increased cancer risk.
There are several differences between BRCA1 and BRCA2 related tumors.
BRCA1-related breast cancers are mostly triple negative.
BRCA2-related breast cancers are mostly ER+.
BRCA1: Located on chromosome 17
>60% risk of the development of female breast cancer
40-60% risk of the development of Ovarian cancer
<5% risk of the development of Pancreatic cancer
7-26% risk of the development of Prostate cancer
BRCA2: On chromosome 13
>60% risk of the development of female breast cancer
1.8% to 7.1% risk of the development of male breast cancer
13-29% risk of the development of Ovarian cancer
5-10% risk of the development of Pancreatic cancer
19-61% risk of the development of Prostate cancer
Increased risk of developing Melanoma
https://www.nccn.org/professionals/physician_gls/pdf/genetics_bop.pdf
Reference: Hirshfield KM, Ganesan S. Triple-negative breast cancer: molecular subtypes and targeted therapy. Curr Opin Obstet Gynecol 2014;26(1):34-40
12.
A 45-year-old female is currently undergoing treatment for her Papillary thyroid cancer. Specifically, she is being evaluated for possible treatment with adjuvant Radioactive Iodine therapy (RAI). Recently, she had a total thyroidectomy for a Papillary thyroid cancer. The surgical pathology report indicated a 1 cm classic Papillary thyroid cancer with no vascular invasion or extrathyroid extension. Her post-operative unstimulated thyroglobulin is < 1 ng/mL. She has no detectable anti-Tg antibodies. She had no clinical signs of lymph node involvement or distant metastases. Which of the following is true regarding RAI treatment in her case?
A . She needs RAI as her age is a poor prognostic risk factor
B . Her tumor meets all the criteria where one would not offer her RAI therapy
C . She does not need RAI as it is only given for patients with differentiated thyroid tumors measuring &amp;gt; 5 cm in size or who have positive lymph node involvement
D . She needs RAI as her gender puts her at a higher risk of developing a recurrence
E . She does not need RAI as she had a thyroidectomy
Your Answer : Option
Not Answered
Correct Answer : Option
B
Explanation:B) Her tumor meets all the criteria where one would not offer her RAI therapy
RAI as adjuvant therapy is not offered to every patient who undergoes surgery for a differentiated thyroid cancer. All her clinical and pathologic features are favorable so one would not offer her adjuvant RAI.
RAI does have toxicity, so one needs to carefully assess if a patient will truly benefit from receiving it as adjuvant therapy.
RAI is typically recommended if any of the following features are present:
--Gross extrathyroidal extension
--Differentiated high-grade carcinoma
--Postoperative unstimulated Tg > 10 ng/mL
--Bulky or >5 positive lymph nodes
--Significant N1b disease
--Vascular invasion
One would selectively recommend adjuvant RAI if any of the following features are seen:
--Tumor >2 cm in size
--High risk histology (ie, poorly differentiated, tall cell, columnar cell, hobnail variant, diffuse sclerosing, and insular)
--Lymphatic invasion
--Cervical lymph node metastases
--Macroscopic multifocality (one focus > 1 cm)
--Postoperative unstimulated thyroglobulin 1-10 ng/mL
--Microscopic positive margin
RAI is not typically recommended if all the following are present:
--Classic papillary thyroid cancer
--Largest primary tumor ≤2 cm in size
--Intrathyroidal
--Unifocal or multifocal (all foci ≤ 1 cm)
--No detectable Tg antibodies
--Postoperative unstimulated Tg < 1 ng/mL or stimulated Tg < 2 ng/mL
--Negative postoperative ultrasound, if done
Reference: Hay ID. Selective use of radioactive iodine in the postoperative management of patients with papillary and follicular thyroid carcinoma. J Surg Oncol 2006;94(8):692-700.
13.
A 35-year-old male presents to see a Hematologist for an evaluation of a possible iron disorder. The patient has been had been having worsening fatigue over the past 6 months. He went to see his PCP who performs a workup. His CBC with Plt/Diff is largely unrevealing. However, his iron studies were abnormal. His ferritin is elevated at 850 μg/L. His transferrin saturation is normal at 20%. The patient is sent to see a Hematologist.
LFTs showed transaminitis with a normal bilirubin. An Ultrasound is ordered that showed some abnormal findings. A dedicated Liver MRI was then performed. The Radiologist reported that there appears to be some evidence of Iron overload in the liver. Interventional Radiology is consulted and performs a liver biopsy. Pathology confirms iron accumulation in the hepatic Kupffer cells.
He has no signs of end organ damage to the heart, endocrine glands or joints. He has 4 siblings, 2 of whom have the same type of disorder. This patient likely has a mutation in which of the following genes?
A . HFE
B . FPN
C . HJV
D . TfR2
E . HAMP
Your Answer : Option
Not Answered
Correct Answer : Option
B
Explanation:B) FPN
Ferroportin Disease (FD) is an autosomal dominant hereditary iron loading disorder associated with heterozygote mutations in the ferroportin-1 (FPN) gene. Ferroportin’s role in the body is to transfer iron from the intestine and macrophages into the bloodstream.
There are two different phenotypes of Ferroportin disease.
Macrophage type:
Loss-of-function mutations of ferroportin are thought to produce a molecule that either does not traffic appropriately to the cell surface or that has limited ability to export iron.
This results in excess accumulation of iron in macrophages, that results in high serum ferritin, normal to reduced transferrin saturation (TSAT), and mild anemia. In young females, hypochromic microcytic anemia may develop that is responsive to iron supplementation. This has also been called macrophage-type (M-type) and is now considered the real ferroportin disease, which is no longer included among HH because of the distinct phenotype.
Hepatic-type (Non-classical):
Gain-of-function mutations produce a ferroportin protein that is resistant to hepcidin and retains full iron export capability. The mutation may affect the binding site for hepcidin (C326) or occurs in its proximity. Iron overload is similarly to what is seen in patients with classic HH.
This results in increased TSAT, high levels of ferritin and hepcidin, and hepatic iron overload. As mentioned above, this is similarl to what is seen in patients with classical HH, although patients with Hepatic-type of iron overload may have a more severe disease phenotype. A liver biopsy in patients with this condition will reveal increased hepatocyte iron.
In patients with Ferroportin disease/Macrophage type, unlike what is seen in patients with classical hemochromatosis, the iron is considerably more prominent in the Kupffer cells than in the hepatocytes. In addition, the fibrosis is primarily sinusoidal.
Ferroportin is the iron transport channel mainly expressed in macrophages and hepatocytes and on the basolateral surface of intestinal enterocytes that is blocked by hepcidin. Ferroportin has also been implicated in the transport of other ions such as manganese.
In the Macrophage type of Ferroportin disease, mutations in FPN1 limit but does not impair the iron export in enterocytes, but it does severely affect the iron transfer in macrophages. This leads to iron trapping in tissue macrophages with reduced iron release to serum transferrin. Hence, patients with this disease have low transferrin saturation. They will often have normal/low transferrin saturation, mild anemia and mild organ disease.
A hallmark feature of this variant of Ferroportin disease is marked iron accumulation in hepatic Kupffer cells, but not as much iron accumulation in the hepatocytes. This is opposite to what is seen in patients with classical hemochromatosis.
The differential diagnosis for this condition includes hereditary hemochromatosis, the syndrome commonly due to either HFE, TfR2, HJV, HAMP or gain of function mutation in FPN1. In these conditions, the elevated ferritin levels is seen in concert with a high transferrin saturation, iron-spared macrophages, and progressive liver parenchymal cell iron load.
These conditions (HFE, TfR2, HJV, HAMP or non-classical FPN1) share a similar pathogenic basis (lack of hepcidin function-activity), biochemical expressivity (high transferrin saturation and high serum ferritin), liver pathologic features (iron accumulation in parenchymal cells with iron-spared Kupffer cells until late stage), damage and disease of distinct target organs (liver, heart, endocrine glands, joints).
An abdominal MRI for patient’s with Ferroportin disease can show iron loading in the spleen, spine and liver.
A non-aggressive phlebotomy regimen is recommended, with careful monitoring of the transferrin saturation and hemoglobin due to the risk of anemia. Family screening is mandatory since siblings and offspring have a 50% chance of carrying the pathogenic mutation.
Of note, non-classical Ferroportin disease occurs with mutations in ferroportin that are resistant to inhibition by the iron regulatory molecule hepcidin, retaining full iron export capability. Patients will normally have high levels of ferritin and hepcidin, increased transferrin saturation, and typical deposition of iron in the hepatic parenchyma. This has also been called hepatic-type ferroportin disease.
https://www.uptodate.com/contents/hfe-and-other-hemochromatosis-genes?search=ferroportin%20disease§ionRank=1&usage_type=default&anchor=H16&source=machineLearning&selectedTitle=1~17&display_rank=1#H16
Reference: Antonello Pietrangelo et al. Ferroportin disease: pathogenesis, diagnosis and treatment. Haematologica 2017 Dec; 102(12): 1972–1984
14.
A 62-year-old male is currently admitted to the hospital recovering from a recent Cholecystectomy.
The patient presented to a local ED for RUQ pain. A U/S and HIDA scan suggested cholecystitis. General surgery was consulted and takes him for a Cholecystectomy. The surgery went well without any complications.
On POD #1, the patient developed worsening right-sided purpura near his abdomen. Labs are drawn and his hemoglobin was found to be 6.2 g/dl, which was down from a preoperative level of 12 g/dl. His Medical team orders a CT scan Abd/Pelvis that reveals a large retroperitoneal bleed. The General surgery team takes him back to the OR and performs a surgical exploration. He is found to have a bleeding vessel that was causing the bleeding. The Surgeon was able to fix this issue.
A Hematologist is consulted as the patient needs to receive several pRBC transfusions but the patient carries a history of IgA deficiency. How should the pRBC be modified to ensure that he has no complications from receiving the transfusion(s)?
A . No specific intervention is needed. IgA deficiency poses no risk for the patient to receive pRBC transfusions
B . Administer premedication with steroids prior to him receiving the pRBC transfusion
C . Gamma irradiate the blood products prior to administering the transfusion
D . Wash the pRBC product prior to giving the transfusion
E . Leukoreduce the pRBC products
Your Answer : Option
Not Answered
Correct Answer : Option
D
Explanation:D) Wash the pRBC product prior to giving the transfusion
IgA is concentrated mostly in the mucosal secretions and is believed to be important in the immune function of the mucosal barrier.
A minority of IgA-deficient individuals are symptomatic. These patients may develop recurrent sinopulmonary infections, autoimmune disorders, gastrointestinal disorders, allergic diseases and rare anaphylactic reactions to blood products.
There are two levels of severity of IgA deficiency that are recognized. A serum IgA level < 7 mg/dL is considered to represent a severe deficiency.
IgA deficiency is the most common human immunodeficiency. The presence of anti-IgA that occurs in an IgA deficient recipient can lead to anaphylaxis if blood products are administered to that patient. This occurs as the anti-IgA antibody of the host reacts against the IgA antigen contained in the donor red cell units.
Most patients with selective IgA deficiency do not form anti-IgA antibodies. These antibodies are usually only found in patients who have undetectable levels of serum IgA.
Patients with selective IgA deficiency can develop urticaria, wheezing, shock and cardiac arrest after receiving transfusion(s). If this were to happen, one must stop the transfusion immediately. Patients may need to receive Epinephrine. One critical point is that patients with IgA deficiency who are transfused with plasma products that contain IgA, will have an _immediate_ reaction to the blood product.
Patients with severe IgA deficiency can experience infusion reactions to blood products containing small amounts of IgA, typically in located in the plasma in the following products: Whole blood, Red blood cells, Granulocytes, Platelets, FFP, Cryoprecipitate and IVIG.
By washing the donor red cell units with saline, centrifuge or removal of the supernatant, the IgA antibodies will be removed. However, this will shorten the shelf-life of red blood cells to less than 24 hours.
Indications to wash Red blood cells:
--Severe allergic reactions
--Removal of maternal antibodies for fetal transfusion
(Hemolytic disease of newborn, Neonatal alloimmune thrombocytopenia)
**Pearl:
Patients who should be screened for anti-IgA antibodies are those patients with severe sIgAD and in patients with partial sIgAD who have experienced an infusion reaction to a blood product in the past. Screening for anti-IgA antibodies allows clinicians to identify patients at risk for infusion reactions and helps these patients become informed about the potential risks of receiving blood products.
https://www.uptodate.com/contents/selective-iga-deficiency-management-and-prognosis?search=febrile%20non-hemolytic%20reaction&topicRef=7947&source=related_link#H6475461
Reference: Brown R et al. An evaluation of the DiaMed assays for immunoglobulin A antibodies (anti-IgA) and IgA deficiency. Transfusion 2008; 48(10): 2057-9
15.
A 68-year-old male has recently been diagnosed with a T2 N0 M0 Urothelial transitional cell cancer of the bladder. A CT Urography and CT Chest reveals no sites of distant metastatic disease. His Urologist performs a TURBT with complete removal of the bladder tumor. The pathology report revealed Muscle invasion. The tumor is a grade 1 transitional cell tumor.
The patient has a long-standing history of Type II Diabetes and hypertension. His baseline Creatinine Clearance is 25 ml/min. His case is currently being discussed at a Multidisciplinary tumor board. What treatment should be recommended for him?
A . Neoadjuvant Cisplatin-based chemotherapy followed by a cystectomy
B . Concurrent chemoradiation
C . Cystectomy alone
D . Radiation alone
E . Choice B or C
Your Answer : Option
Not Answered
Correct Answer : Option
E
Explanation:E) Choice B or C
For patients who present with muscle invasive urothelial cancer of the bladder that is T2, T3, T4 or Tany N+, the standard of care treatment is to offer neoadjuvant Cisplatin based chemotherapy (dose-dense MVAC preferred with GCSF support) followed by a cystectomy.
Guidelines have suggested that if a patient with muscle invasive urothelial cancer is not deemed to be a candidate for Cisplatin (ie, renal dysfunction), that he or she should not receive neoadjuvant chemotherapy. Carboplatin in the treatment of this malignancy is not felt to be adequate treatment and should not be substituted for Cisplatin.
The data on the benefit of offering adjuvant chemotherapy for patients with bladder cancer is less robust. However, guidelines do suggest that for those patients who do not receive neoadjuvant chemotherapy, one can consider offering adjuvant chemotherapy based on post-operative pathology. Patients with a T3 to T4 tumor or positive nodes can be considered for adjuvant chemotherapy if they did not receive any chemotherapy preoperatively.
Of note, if a patient undergoes a frontline Cystectomy and the tumor is pT2 or less with no nodal involvement or LVI, then offering adjuvant chemotherapy is not recommended. This is important as often a Medical Oncologist will see a patient only after the patient has undergone a cystectomy. Unfortunately, in these cases there was no opportunity to give neoadjuvant chemotherapy.
This patient has a T2 urothelial cancer and is not a candidate to receive Cisplatin as part of the treatment regimen. One would proceed with either cystectomy or concurrent chemoradiation with 5-FU/Mitomycin C or low-dose Gemcitabine after a maximal debulking TURBT. Concurrent chemoradiation does has Category 1 evidence to offer in this setting as does neoadjuvant Cisplatin-based chemotherapy followed by a radical cystectomy. For this patient, would likely offer concurrent chemoradiation.
As mentioned above, given his renal dysfunction, he is not a candidate to receive Cisplatin as a treatment.
The guidelines for Cisplatin dosing based on renal dysfunction are not standard. However, some guidelines recommend the following:
GFR (ml/min) >60 Give 100% of the dose
45-59 Give 75% of the dose
<45 Consider Carboplatin [Depending on the tumor type]
Some will use split dose cisplatin in patients who have a low CrCl. One needs to be careful offering Cisplatin to patients with a CrCl that is < 60 mL/min.
For patients on dialysis, one will normally give 50% of the Cisplatin dose. Dialysis should be performed within 3 hours after the dose of Cisplatin is administered.
Reference: https://www.nccn.org/professionals/physician_gls/pdf/bladder.pdf
16.
A 14-year-old male has a history of severe Hemophilia A with Factor VIII levels < 1%. He developed bleeding in his right knee at 1 year of age. Since that time, he has been receiving prophylaxis with Factor VIII, 30 units/kg three times a week. Despite this, he still required many Factor VIII infusions for breakthrough bleeding episodes.
When he was around 8 years old, he was found to have an inhibitor and he has required bypassing agents to control episodes of bleeding. Despite this, he continues to have several bleeds every year especially in his bilateral knees. Which medication should one consider adding at this time for prophylaxis to help control his episodes of bleeding?
A . None
B . Factor IX infusions
C . Rituximab
D . IVIG
E . Emicizumab
Your Answer : Option
Not Answered
Correct Answer : Option
E
Explanation:E) Emicizumab
The FDA has approved emicizumab-kxwh for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adult and pediatric patients with hemophilia A (congenital factor VIII deficiency) with and without factor VIII inhibitors.
Emicizumab bridges activated factor IX and factor X to restore the function of activated factor VIII, which is deficient in patients with hemophilia A.
Patients enrolled in the HAVEN 1 study were 12 years of age or older. Those who had previously received episodic treatment with bypassing agents were randomly assigned in a 2:1 ratio to emicizumab prophylaxis (group A) or no prophylaxis (group B). The primary end point was the difference in bleeding rates between group A and group B. Participants who had previously received prophylactic treatment with bypassing agents received emicizumab prophylaxis in group C.
A total of 109 male participants with hemophilia A with inhibitors were enrolled. The annualized bleeding rate was 2.9 events among participants who were randomly assigned to emicizumab prophylaxis versus 23.3 events among those assigned to no prophylaxis. This represents a significant difference of 87% in favor of emicizumab prophylaxis (P<0.001).
A total of 22 participants in group A (63%) had zero bleeding events, as compared with 1 participant (6%) in group B. Among 24 participants in group C who had participated in a noninterventional study, emicizumab prophylaxis resulted in a bleeding rate that was significantly lower by 79% than the rate with previous bypassing-agent prophylaxis (P<0.001).
Overall, 198 adverse events were reported in 103 participants receiving emicizumab prophylaxis; the most frequent events were injection-site reactions (in 15% of participants). Thrombotic microangiopathy and thrombosis were reported in 2 participants each (in the primary analysis) who had received multiple infusions of activated prothrombin complex concentrate for breakthrough bleeding. No antidrug antibodies were detected.
As mentioned above, Emicizumab also has FDA approval for patients with Hemophilia A who do not have an inhibitor.
The HAVEN 3 study tested emicizumab as prophylaxis in 152 patients aged 12 years or older with severe hemophilia A (Factor VIII activity <1%) who did not have an inhibitor. Most of these patients were only receiving episodic therapy for bleeding.
Compared with controls receiving only episodic therapy with factor VIII, individuals assigned to emicizumab prophylaxis had a dramatically reduced annualized bleeding rate (38 events versus 1.5 and 1.3 events at the two dosing protocols [1.5 mg/kg once weekly or 3 mg/kg every other week, respectively)
All controls had at least one bleeding event during the study (24 weeks), whereas more than half of participants in both emicizumab groups had no bleeding events during the study.
In the group of 48 patients who had been receiving routine factor VIII prophylaxis, transition to emicizumab reduced the annualized bleeding rate by 68 percent.
Johannes Oldenburg et al. Emicizumab Prophylaxis in Hemophilia A with Inhibitors. N Engl J Med 2017; 377:809-818
Reference: Mahlangu J et al. Emicizumab Prophylaxis in Patients Who Have Hemophilia A without Inhibitors. N Engl J Med. 2018;379(9):811.
17.
A 64-year-old year-old male has recently completed concurrent chemoradiation for Stage IIIB lung adenocarcinoma. He received Cisplatin/Etoposide x 2 cycles during his radiation treatment. He tolerated therapy quite well with no major side effects. A restaging CT scan was performed 4 weeks after he completed chemoradiation. The scan reveals that he has had significant reduction of his tumor mass. There are no signs of new or distant metastatic disease.
The tumor is sent for Next Generation Sequencing. No actionable mutations are seen and the PD-L1 TPS=0%. Which therapy should be given at this time for consolidation therapy?
A . Pemetrexed
B . Cisplatin and Etoposide x 2 cycles
C . Pembrolizumab
D . Durvalumab
E . Observation
Your Answer : Option
Not Answered
Correct Answer : Option
D
Explanation:D) Durvalumab
Most patients with Stage III unresectable, NSCLC will have subsequent disease progression despite receiving definitive chemoradiotherapy.
The PACIFIC study was a phase 3 study that compared the anti–programmed death ligand 1 antibody durvalumab as consolidation therapy with placebo in patients with stage III NSCLC who did not have disease progression after two or more cycles of platinum-based chemoradiotherapy.
Patients were randomly assigned in a 2:1 ratio, to receive durvalumab (10 mg/kg) or placebo every 2 weeks for up to 12 months. The study drug was administered 1 to 42 days after the patients had received chemoradiotherapy.
Of 713 patients who underwent randomization, 709 received consolidation therapy (473 received durvalumab and 236 received placebo).
The median progression-free survival from randomization was 16.8 months with durvalumab versus 5.6 months with placebo (HR=0.52; P<0.001); the 12-month progression-free survival rate was 55.9% versus 35.3%, and the 18-month progression-free survival rate was 44.2% versus 27.0%.
The response rate was higher with durvalumab than with placebo (28.4% vs. 16.0%; P<0.001), and the median duration of response was longer (72.8% vs. 46.8% of the patients had an ongoing response at 18 months).
The median time to death or distant metastasis was longer with durvalumab than with placebo (23.2 months vs. 14.6 months; P<0.001). Grade 3 or 4 adverse events occurred in 29.9% of the patients who received durvalumab and 26.1% of those who received placebo; the most common adverse event of grade 3 or 4 was pneumonia (4.4% and 3.8%, respectively).
A total of 15.4% of patients in the durvalumab group and 9.8% of those in the placebo group discontinued the study drug because of adverse events.
Of import, the PD-L1 status of the tumor does not influence whether to offer Durvalumab as consolidation therapy. Even though the patient in this question has a tumor with a PD-L1 TPS score of 0%, he should absolutely be considered for Durvalumab.
Reference: Scott J. Antonia et al. Durvalumab after Chemoradiotherapy in Stage III Non–Small-Cell Lung Cancer. N Engl J Med 2017; 377:1919-1929
18.
A 62-year-old male presents to see his Oncologist to discuss treatment options for his Stage IV Kidney cancer.
One year ago, he had presented to see his Primary Care Physician for evaluation of a 1-month history of worsening right flank pain and hematuria. An Ultrasound is ordered showing a 6 cm right kidney mass. Subsequently, the patient has a CT C/A/P IV contrast performed that confirmed the Right kidney mass. No other sites of disease are seen. The patient is referred over to see a Urologist.
The patient undergoes a radical nephrectomy. Pathology reveals that the patient has a Stage I, Collecting duct cancer. The patient undergoes close surveillance with imaging. Unfortunately, he was recently found to have widely metastatic disease with disease in his bilateral lung fields. A biopsy of a lung lesion reveals a collecting duct cancer. Next generation sequencing of the tumor is performed revealing no actionable mutations. Which therapy should be offered?
A . Sutent
B . Pazopanib
C . Axitinib
D . Gemzar + Platinum
E . Everolimus
Your Answer : Option
Not Answered
Correct Answer : Option
D
Explanation:D) Gemzar + Platinum
Collecting (Bellini) duct carcinoma is a rare subtype of renal cell cancer. It acts aggressively and up to 40% of patients have metastatic disease at initial presentation. Patients with this malignancy will normally have a poor prognosis. Collecting duct carcinoma shares biologic features with urothelial carcinoma.
For patients with collecting duct or medullary subtype of kidney cancer, partial responses have been observed with cytotoxic chemotherapy (Carboplatin + Gemcitabine, Carboplatin + Paclitaxel, or Cisplatin + Gemcitabine) and other platinum-based chemotherapies currently used for urothelial carcinomas.
One group performed a systematic review of the literature on the management options for collecting duct cancer.
The best studied therapy was felt to be Gemcitabine/Cisplatin. The role of targeted therapy (tyrosine kinase inhibitors such as sunitinib or sorafenib) and immunotherapy in the management of collecting duct carcinoma has not been as well established.
A prospective multicentre phase II study evaluated the efficacy of gemcitabine and either cisplatin or carboplatin for patients with Stage IV collecting duct cancer.
Participants received 21-day cycles of gemcitabine 1250 mg/m2 on days 1 and 8, plus cisplatin or carboplatin 70 mg/m2 (based on renal function) on day 1 (n = 23 gemcitabine, n = 12 cisplatin, n = 6 carboplatin, and n = 5 cisplatin then carboplatin). Participants underwent a median of 6 cycles of treatment (range: 1–8 cycles).
Participating patients achieved a 26% partial or complete response rate with 1 complete response. Another 10 patients (44%) experienced disease stabilization, and 7 had progressive disease (30%). Progression-free survival was 7.1 months and overall survival was 10.5 months.
Reference: S Dason et al. Management of renal collecting duct carcinoma: a systematic review and the McMaster experience. Curr Oncol 2013 Jun; 20(3): e223–e232.
19.
A 66-year-old male presents to see a Hematologist/Oncologist for evaluation of diffuse lymphadenopathy located throughout his body that has been getting worse over the past 6 months. His exam reveals lymphadenopathy in his cervical neck, axilla and inguinal area. He has a palpable spleen. He denies having any constitutional B symptoms.
An excisional biopsy is performed of a cervical lymph node. Pathology confirms that he has some type of lymphoma. The pathologic specimen is still being analyzed, however, the lymphoma is: CD10-, CD5+, CD23-, Cyclin D1- and SOX11+. His Ki67 is 40%.
A PET-CT is performed that confirms disease throughout his body. What is the most likely lymphoma that this patient has?
A . Follicular lymphoma
B . CLL/SLL
C . Mantle cell lymphoma
D . DLBCL
E . Marginal zone lymphoma
Your Answer : Option
Not Answered
Correct Answer : Option
C
Explanation:C) Mantle cell lymphoma
Mantle cell lymphoma (MCL) is usually an aggressive B cell lymphoma defined by cyclin D1 (CCND1) overexpression. The characteristic translocation seen in this lymphoma is t(11;14).
The Mantle Cell Lymphoma International Prognostic Index (MIPI) has been designed to stratify MCL patients into risk groups (low, intermediate or high risk) based on clinical prognostic factors, such as age, performance status, white blood cell count and lactate dehydrogenase (LDH) level.
Ki-67 expression over 30% predicts for a more aggressive clinical course. Mantle cell lymphoma that harbors a TP53 mutation or is the blastoid subtype is associated with more aggressive behavior.
SOX11 is a diagnostic antigen seen in MCL. Cyclin D1- (CCND1 negative) Mantle cell lymphomas are not well characterized. SOX11 has been identified as a reliable biomarker of MCL that is also expressed in the cyclin D1 negative variant. Data sets have demonstrated that patients who have Cyclin D1 MCL (SOX11+) have disease that is clinically and biologically similar to patients with conventional cyclin D1(+) MCL.
The most common biomarker for indolent disease:
SOX11- [IGHV mutated]
Typical clinical presentation for indolent, SOX11- Mantle cell lymphoma is:
Leukemic non-nodal CLL-like with splenomegaly, GI or Blood/Bone marrow involvement only, low tumor burden, Ki67 proliferation fraction <10%
Many patients with indolent Mantle Cell Lymphoma can be observed.
In addition to CCND1,
Reference: Lena Nordström et al. SOX11 and TP53 add prognostic information to MIPI in a homogenously treated cohort of mantle cell lymphoma – a Nordic Lymphoma Group study. Br J Haematol 2014 Jul; 166(1): 98–108
20.
A 58-year-old male presents urgently to the ED for evaluation of RLE pain and swelling. An Ultrasound is performed that reveals a DVT of the right posterior tibial vein. Two days prior to the development of the RLE swelling, he had come back on a non-stop plane ride from South Korea.
The patient is up to date with his age-appropriate cancer screening tests. He has a history of Type II DM and his calculated CrCl=35 mL/min.
Hematology is consulted on this case. This is felt to be a provoked clot. The patient needs to start on anticoagulation . However, in addition to his kidney dysfunction, the patient has a history of HIT that occurred 2 years ago after he received prophylactic enoxaparin during an inpatient admission for multifocal pneumonia. However, he did not have any clotting event (no DVT, stroke) with that HIT episode. He just had developed thrombocytopenia during that time. The HIT Antibody and Serotonin release assay were both positive during that admission. His platelet count eventually recovered back to normal.
Of the following choices, what is the best option for him to manage his DVT?
A . IVC Filter
B . Coumadin 5 mg daily
C . Enoxaparin 1.5 mg/kg x 5 days along with Coumadin 5 mg daily
D . Xarelto 15 mg po bid x 3 weeks then 20 mg po daily
E . Heparin gtt x 5 days along with Coumadin 5 mg daily
Your Answer : Option
Not Answered
Correct Answer : Option
D
Explanation:D) Xarelto 15 mg po bid x 3 weeks then 20 mg po daily
Xarelto is a factor Xa inhibitor that is a highly effective medication used in the treatment of patients who develop a DVT/PE.
It is an approved medication that is given in the following situations:
--To reduce the risk of stroke and embolism in patients with nonvalvular atrial fibrillation
--Treatment of a DVT and PE and for the reduction in the risk of recurrence of a DVT and of PE
--DVT prophylaxis for patients who are undergoing knee/hip replacement surgery
Given this patient’s history of HIT, it would not be ideal to rechallenge him with heparin or low-molecular weight heparin.
Coumadin needs several days to become therapeutic and thus the patient would need a bridge with a heparin product for at least 5 days.
One advantage of Xarelto (or any of the Direct Oral anticoagulants) is that no bridging therapy is needed and it can be given as monotherapy. Xarelto has been shown to be an effective medication for those patients who have a history of HIT (or who have a current diagnosis of HIT).
Mothers who are nursing should either discontinue this drug or stop nursing. Patients with renal impairment will need to avoid or adjust the dose of this medication based on CrCl and treatment indication. Patients with severe hepatic impairment (Child-Pugh B and C hepatic impairment or with any degree of hepatic disease associated with coagulopathy), should avoid using this medication.
For patients being treated for DVT, PE and for the reduction in the risk of recurrence of DVT and of PE, one should avoid Xarelto if they have a CrCl <30 mL/min.
Reference: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/022406s015lbl.pdf