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Updates found with 'last line platinum'

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Updates found with 'last line platinum'

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%)
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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
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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.
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Question- Is it possible to cure CML (CHRONIC MYELOID LEUKEMIA) one of the types of blood cancer with tablets (bcr-abl kinase inhibitor) eg imatinib, nilotinib or dasatinib?Answer- We don’t know the answer yet, but studies are now looking for stopping these tablets in patients who achieve desired response with them. This concept is called TFR (Treatment Free Remission)Question- What is TFR?Answer- TFR is defined as maintenance of less than minimal residual or undetectable BCR-ABL transcript level even after stopping BCR-ABL kinase inhibitors.Question – Which patients are ideal candidates for TFR?Answer- Ideal candidates are CML-Chronic phase patients who maintain stable and continuous DMR (deep molecular response) for more than 2 years, without any history of failure of response to any of the available TKIs (Tyrosine kinase inhibitor).Question – What percentage of these carefully selected patients maintain their TFR?Answer- Close to 50% patients maintain TFR for more than 1 year.Question- Important checklist before offering TFR?Answer- Patient compliance is of paramount importance, because regular BCR-ABL monitoring is required to detect reappearance of BCR-ABL levels and prevent transformation into accelerated or blastic phase of CML.Question- What is imatinib withdrawal syndrome?Answer- An imatinib withdrawal syndrome consist of diffuse myalgia/ arthralgia encountered after stopping TKI. Question – Is maintenance of TFR equivalent to cure?Answer- We do not know yet and longer follow up is required to answer this question.
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Pregnancy and cancer: A challenge for obstetrician and oncologist!As the age of child birth is delayed we may be seeing more cases with cancer in pregnancy.At present estimated incidence of cancer in pregnancy is estimated to be around 1 in 1000 livebirths worldwide.Gestational cancer is the term given to cancer occuring in pregnancy and up to one year postpartum.Like in general population the symptoms of cancer are not unique and they mimic with more commonly occuring diseases, similarly many of the symtoms of cancer in pregnancy are often suspected to be due to underlying pregnancy and other common conditions leading to delay in diagnosis.Tissue diagnosis is key to confirm diagnosis in solid tumors like breast , cervix etc.While for hematological malignancy CBC with PBF is basic investigation to start with and further work up is directed based on clinical suspicion of leukemia or lymphoma.Imaging workup for diagnosis and staging should keep in mind that radiation exposure to fetus should be as low as possible.Radiation may lead to either spontaneous abortion, teratogenesis or carcinogenesis.It should be kept in mind that though teratogenesis is dose dependent , with doses greater than 50mGy continue to be more and more teratogenic. However carcinogenesis is not dose dependent and can occur at any dose leading to increased risk of childhood cancers with a risk of 3-4 times as compared to general population.Chest X-ray , mammography with abdominal shield are safe.CT chest can be done with abdominal shielding.MRI without contrast is preferred modality instaging Brain, Bone, Abdomen and pelvis.Gadolinium contrast can be used if absolutely necessary keeping in mind that there is limited data for its safety in pregnancy.Iodinated contrast may be associated with neonatal thyroid disorder and if used , a careful screening of neonatal thyroid functioning should be done.Overall breast cancer is the most common cancer seen in pregnancy, which usually present in stage Il and lll. While cervical cancer is most common gynecological cancer seen in pregnancy and in 75% patients it is diagnosed in stage l.Treatment of cancer in pregnancy is complex and it should involve multidisciplinary team approach including obstetrician, neonatologist and oncology team.Surgery for cancer can be done during any trimester of pregnancy, with increased risk of miscarriage during first trimester. Pelvic and abdominal surgery are associated with increased feto maternal complications and it should be discussed with the patient.Chemotherapy is avoided in first trimester. In second and third trimester chemotherapy can be given , keeping in mind that not all chemotherapy drugs are equally safe. Platinum chemotherapy is associated with small for gestation and paclitaxel is associated with increased NiCU admission based on recent paper in lancet oncology in 2018 which analysed outcome of around 1300 pregnant cancer patients.As far as targeted therapy is concerned , trastuzumab should be avoided in pregnancy as it is associated with oligohydramnios. Rituximab is used in treatment of NHL and when used in pregnancy it is associated with fetal B cell depletion , the risk of which should be discussed with patients and though the recovery may take up to 6 months in neonate but it is usually complete.Radiation treatment should be delayed till delivery for reasons discussed above.
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