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All cases of classical Hodgkin's lymphoma are CD 30 positive and LCA negative. CD 20 positivity and CD15 negative IHC profile on biopsy of lymph node is seen in around 10%. The presence of such an IHC profile should be kept in mind before diagnosis of Hodgkin's lymphoma is excluded.
Maintenance with PARP inhibitor is the way forward in ovarian cancer: Median PFS in platinum sensitive relapse carcinoma ovary is approximately 10 months. 20% of high grade serous carcinoma ovary have somatic or germline mutation in BRCA gene. Single stranded DNA breaks are repaired Base excision repair pathways of which PARP ( poly ADP ribose polymerase) enzymes are one of the key members. In presence of PARP inhibitors these single stranded breaks are converted into double stranded breaks and the repair of these double stranded breaks require intact Homologous recombination repair pathway. BRCA proteins are integral part of these Homologous recombination pathway. In presence of BRCA gene muatation the double stranded breaks produced in presence of PARP inhibitor bring about lethal damage to the cancer cells. Olaparib is the most extensively studied PARP inhibitor and it is approved in BRCA mutation positive relapse high grade carcinoma ovary as single agent after 3 or more lines of chemotherapy. Also Olaparib has been approved as maintenance in both BRCA mutated and wild type patients in relapse platinum sensitive high grade carcinoma ovary who attain CR or PR to last line platinum doublet. The reported PFS in this setting is around 18 months in BRCA mutated (SOLO-2 trial-using tablet olaparib 300mg twice daily) v/s 9 months in BRCA wild type based on STUDY- 19 Trial (Capsule Olaparib 400mg twice daily). It is important to note that about 15% patients remain progression free at 5 years in study-19 trial on Olaparib ( these long term progression free survival benefited both BRCA wild type and BRCA mutated subgroup) . Niraparib based on the result of NOVA trial (300 mg once daily) got approval in maintenance for both BRCA mutated and wild type patients in relapse platinum sensitive high grade carcinoma ovary who attain CR or PR to last line platinum doublet. Rucaparib at a dose of 600mg twice daily awaits its approval in similar setting with the promising results of the ARIEL3 presented in ESMO 2017. Main toxicity of Olaparib is anemia, nausea and fatigue. (Discontinuation rate 6%) Main toxicity of Niraparib is nausea and haematological (Thrombocytopenia> Anemia>Neutropenia) (Discontinuation rate 15%) Main toxicity of Rucaparib is anemia and elevation of liver enzyme (Discontinuation rate 13%)
IMMUNOTHERAPY IN LUNG CANCER- THE FUTURE OF CANCER CARE. Any cancer and lung cancer in particular creates a highly immunosuppressive environment locally i.e. our bodies immune cells are unable to recognize cancer cells. This is made possible by expression of certain proteins on surface of cancer cells which in turn binds to checkpoints like CTLA-4 and PD-1 present on surface of T-cells . This binding triggers a negative signal and stops T-cells from killing cancer cells. Immunotherapy drugs blocks the CTLA-4 and PD-1 which are checkpoints on T-cells , alternatively other drugs bind to the ligands present on surface of tumor cells. This leads to reactivation of the bodies ability to kill these cancer cells. Pembrolizumab is a immunotherapy drug that is a PD-1 inhibitor and it is approved in both 1st and 2nd line metastatic non small cell lung cancer. There is a IHC test that has to be done with a approved antibody for detecting the expression of PD-L1 ligand in tumor tissue. In the 1st line pembrolizumab is used in patients when PD-L1 expression is more then 50%.In the 2nd line the drug is used when expression >1%. The drug recently got its approval in 1st line in combination with chemotherapy based on the results of one of KEYNOTE trial. Nivolumab is approved in 2nd line irrespective of the PD-L1 expression for metastatic NSCLC. Immunotherapy drugs leads to long term stabilization of metastatic disease in approximately 20% of patients. Cost is a major limitation which restricts its use in developing country
Decoding Lynch syndrome -- Colorectal cancer(CRC) Lynch syndrome is the most common cause of inherited Colorectal cancer (CRC-large intestine cancer). It constitutes 3% of all newly diagnosed colorectal cancer burden. In lynch syndrome there is germline mutation in DNA mismatch repair (MMR) genes. It has a autosomal dominant pattern of inheritance. MLH1; MSH2; MSH6; PMS-2 are genes that are commonly mutated which results in changes in repetitive nucleoside sequences known as microsatellite. These changes in microsatellites ie microsatellite instability (MSI) result in change of expression of genes involved in cell growth. MSI is not specific for Lynch syndrome but can be seen in other sporadic CRC patients. Progression of adenoma to carcinoma in these families and patients takes 3 years as compared to a decade or longer in sporadic cancers. Screening for Lynch syndrome is done using IHC or MSI testing from tumor tissue but are confirmed by gene sequencing in somatic or germline specimen. Life time risk of developing CRC in lynch family is 10-47% depending on the gene mutated. CRC in lynch involve usually right colon and the survival in patients with lynch syndrome developing CRC is better. Screening strategy for lynch family include Colonoscopy (every 1-2 years) beginning 5 years prior to the age of the earliest diagnosed CRC patient in family. Prophylactic hysterectomy and bilateral salphingo-oopherectomy after age of 40 years is recommended for preventing endometrial cancer.
Redefining low grade glioma ( a type of brain tumor ) using WHO 2016 classification: Clinical presentation of low grade glioma is usually with new onset seizure Radiologically low grade glioma are hyperintense on T2 MRI images and do not show contrast enhancement. Morphologically diffuse low grade glioma were classified as astrocytoma, oligodendroglioma and oligoastrocytoma. Now IDH 1 and 2 mutation status is used classify them into 1) IDH wild type astrocytoma -- the ones with more aggressive biology and lower survival. 2)IDH mutated without 1p/19q codeletion low grade glioma are having intermediate prognosis. 3)IDH mutated with 1p/19q codeletion are morphologically oligodendroglioma and are associated with best prognosis. Other gene mutation involving TERT promoter, p53 , EGFR can be used for more accurate subtyping. Use of molecular studies has eliminated the mixed histology ie oligoastrocytoma.
Is it possible to avoid chemotherapy in Breast Cancer? Breast cancer is a heterogeneous disease. This heterogeneity was initially assessed by clinical factors comprising of age, stage, grade, hormone-her2nu status and presence or absence of lymphovascular invasion. Patients with Early Breast cancer (T1-T2 N0-3) of luminal A type (ER positive ;PR more then 20% and her nu negative and ki67 less 10%) is a subset comprising of 1/3 rd of patients. In this clinical group of patients we have gene expression panel which can further help in prognosticating and predicting benefit of hormonal treatment alone. 1st generation gene panel includes Mammaprint and Oncotype Dx. 2nd generation gene panel includes Prosigna, Endopredict. So yes it is possible to omit chemotherapy in selected group of Breast cancer patients. Gene panels should be used in combination with classical clinical factors. Cost is a limitation for the use of these gene panels in Indian context.