Chemotherapeutic agents, endocrine therapy and radiotherapy used in the management of breast cancer are known to cause decreased bone mineral density, and thus, increased incidence of fractures. A ...majority (~60%) of the breast cancer patients in India are either estrogen (ER) or progesterone hormone receptor (PR) positive. Adjuvant treatment with aromatase inhibitors (AIs) is the treatment mainstay for hormone-sensitive disease in postmenopausal (PM) women, with reduced bone mineral density (BMD), which results in increased fracture rates. Zoledronic acid, alendronate, risedronate and denosumab have been the agents of choice for managing bone loss. Denosumab 60 mg is approved for gaining bone mass in women with breast cancer who are at high risk for fracture following adjuvant AI treatment. The phase III HALT-BC data indicate an improvement in BMD with denosumab and a 50% reduction in clinical fractures, with significant improvements seen at the lumbar spine, distal third of the radius, and total hip. Denosumab has several advantages over other bone modifying agents such as subcutaneous self-administration by the patient themselves, no requirement of hospitalization, no dose modifications in renal impairment, and low incidence of acute phase anaphylactic reactions. We review the available evidence of denosumab for managing bone loss in non-metastatic breast cancer patients. Keywords: nonmetastatic breast cancer, postmenopausal women, denosumab, bone loss, bone mineral density, fracture
Angiosarcoma is an incredibly rare type of malignancy, accounting for only 1%-2% of all soft-tissue sarcomas globally. It is clinically, pathologically and radiologically difficult to diagnose ...angiosarcoma owing to its varied presentation with little or no well-defined imaging findings.Kasabach-Merritt syndrome is also a lesser-heard entity which carries extremely poor prognosis. It is primarily seen in infants with vascular malformations and in kaposiform haemangioendothelioma. It is a condition of consumptive coagulopathy and only few of the cases have been reported so far in the adults with a background of angiosarcoma.This report presents the case of a male in his 70s who was diagnosed with metastatic angiosarcoma and experienced a complicated disease course due to Kasabach-Merritt syndrome.
In advanced Renal Cell Carcinoma (aRCC), systemic therapy is the mainstay of treatment, with no or little role for surgery in these patients. Tyrosine kinase inhibitors (TKIs) and immune-oncological ...(IOs) therapies, either alone or in combination, are recommended in these patients depending on patient and tumour factors. The sequencing of therapies is critical in RCC because the choice of subsequent line therapy is heavily dependent on the response and duration of the previous treatment. There are additional barriers to RCC treatment in India. Immunotherapy is the cornerstone of treatment in ccRCC, but it is prohibitively expensive and not always reimbursed, effectively putting it out of reach for the vast majority of eligible patients in India. Furthermore, in advanced RCC (particularly the clear cell variety), Indian oncologists consider the disease burden of the patients, which is particularly dependent on the quantum of the disease load, clinical symptoms, and performance status of the patient, before deciding on treatment. There are no India-specific guidelines for clear cell RCC (ccRCC) treatment or the positioning and sequencing of molecules in the management of advanced ccRCC that take these country-specific issues into account. The current consensus article provides expert recommendations and treatment algorithms based on existing clinical evidence, which will be useful to specialists managing advanced ccRCC.
EGFR-TKIs have changed the landscape of metastatic NSCLC treatment with a significant improvement in survival of EGFRm patients compared to wild-type EGFR. Even with the newer third generation EGFR ...TKIs like, Osimertinib, which has proven efficacy against the resistance mutation of EGFRm T790M, progression eventually occurs. There are limited treatment options for patients with metastatic EGFRm NSCLC with other acquired resistance. Therefore, novel therapeutic combination strategies are being researched to overcome potential resistance to EGFR-TKI-targeted therapy. The ICIs targeting the programmed cell death-1 pathway in patients with EGFRm NSCLC were greatly anticipated based on preclinical studies showing increased PD-L1 expression. In clinical settings, this increased expression did not translate into a survival benefit. Treatment with ICIs failed to positively affect EGFRm patients because of multiple reasons: nonsynonymous tumor mutational burden, lower PD-L1 expression in tumors, and cancer cells utilizing alternate immune escape mechanisms. The NCCN guidelines currently do not recommend immunotherapy in patients with metastatic EGFRm NSCLC. Recently, a subgroup analysis in the IMpower150 study provided a signal for overall survival of atezolizumab with bevacizumab plus chemotherapy in EGFRm-TKI progressed patients. Based on these encouraging findings, several combinations of ICIs and EGFR-TKIs are being evaluated in TKI-failed EGFRm patients. These regimens might provide a favorable therapeutic effect by combining higher response rates of TKIs and durable disease control of ICIs. However, further research is warranted to understand the exact underlying molecular and cellular mechanisms responsible for the clinical benefits. In this article, we explored the TKI failed metastatic EGFRm NSCLC, reviewed the available clinical data of ICI use in metastatic EGFRm NSCLC, and discussed its emerging role as a combination regimen in this patient population.
Synovial cell sarcoma is an extremely rare tumor of mesenchymal origin. It commonly affects the soft tissues of the extremities but could possibly origin from the head and neck, heart, lung, pleura, ...mediastinum, esophagus, abdominal wall and the mesentery, and retroperitoneum. Primary synovial sarcoma of pleura, mediastinum, and lung have been reported. Primary synovial sarcoma of the diaphragm has not been reported to the best of our knowledge. We report a case of primary synovial cell sarcoma of the diaphragm presenting as a recurrent pleural effusion and pain in the left hypochondrium managed with multimodality approach.
Abstract
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Vikas Ostwal
Background
Ramucirumab is considered a standard of care as second-line therapy (CT2) in advanced gastric cancers (AGCs). The aim of this ...study was to assess practice patterns and outcomes with ramucirumab among Indian patients with AGCs.
Materials and Methods
A computerized clinical data entry form was formulated by the coordinating center's (Tata Memorial Hospital) medical oncologists and disseminated through personal contacts at academic conferences as well as via email for anonymized patient data entry. The data was analyzed for clinical characteristics, response rates, and survival outcomes.
Results
A total of 26 physicians contributed data, resulting in 55 patients receiving ramucirumab and being available for analysis. Median age was 53 years (range: 26–78), 69.1% of patients had greater than two sites of disease, and baseline Eastern Cooperative Oncology Group's performance score (ECOG PS) ≥ 2 was seen in 61.8% of patients. Ramucirumab was used as monotherapy in 10.9% of patients, while the remaining 89.1% received ramucirumab combined with chemotherapy. Median event-free survival (EFS) and median overall survival (OS) with ramucirumab were3.53 months (95% CI: 2.5–4.57) and 5.7 months (95% CI: 2.39–9.0), respectively. Common class specific grade adverse events seen with ramucirumab included gastrointestinal (GI) hemorrhage (9.1% - all grades) and uncontrolled hypertension (Grade 3/4 - 3.6%).
Conclusions
Ramucirumab appears to have similar efficacy in Indian AGC patients when compared with real-world data from other countries in terms of median EFS, but OS appears inferior due to more patients having borderline ECOG PS and high metastatic disease burden. GI hemorrhages appear more common than published data, although not unequivocally related to ramucirumab.
Abstract Primary spindle cell sarcoma of the left atrium is an extremely rare tumour. Surgical excision is the mainstay of treatment since it responds poorly to chemotherapy or radiotherapy. In spite ...of all the treatment, the prognosis remains poor due to inadvertent delay in diagnosis, few therapeutic options and propensity to metastasize. We present a 47-year-old male who underwent a surgical excision of a left atrial mass in February 2010. It was proved to be a high-grade spindle cell sarcoma on histopathology. He presented again in October 2010 with recurrence of the tumour for which he was re-operated. However, the tumour recurred again within one month, to which the patient succumbed.
Sjögren’s syndrome (SS) is a chronic slowly progressive autoimmune disorder characterized by symptoms of oral and ocular dryness, exocrine dysfunction, and lymphocytic infiltration of exocrine ...glands. Multiple myeloma (MM) is a bone-marrow-based malignant neoplasm of plasma cells associated with serum/urine monoclonal paraproteins and lytic skeletal lesions. There have been very few reported cases of MM, who had SS as the first presentation. We report a case of a woman diagnosed with Sjögren’s syndrome, who was later suspected to have multiple myeloma on serum protein electrophoresis. Fluorescence in situ hybridization (FISH) was carried out to check for deletions of loci 13q14.3, ATM, p53, and IGH (14q32) rearrangements on a bone marrow aspirate. Monosomy 13 was observed in 49% of cells, and a rearrangement at the IGH locus was seen in 42% of cells. To determine the partner chromosome associated with the IGH rearrangement, further FISH tests were set up for t(4;14)(p16;q32) followed by t(14;16)(q32;q22) on fresh slides. The test was negative for t(4;14) but positive for t(14;16) in 27% of cells. This confirmed the diagnosis of MM. We report the first case from India, having an association of Sjögren’s syndrome with multiple myeloma, which showed t(14;16) and monosomy 13 by FISH analysis.
Abstract 4456
Dasatinib is a highly effective oral TKI for CML at various stages of the disease. The most common non-hematologic side-effect is pleural effusion. The exact mechanism of this pathology ...remains to be fully elicited, although studies report it to be an immunological phenomenon. Current literature shows dasatinib alone to be the cause of such effusions. More recently, pulmonary hypertensions have been reported on dasatinib therapy.
However, in our cohort of CML patients receiving dasatinib as a first or second line therapy, other pathologies were documented. Grade 2/3 unilateral pleural effusions were detected in 3 patients.
A 31 yr old male with CML-CP was on first line dasatinib 100 mg OD and CCyR was documented at 3 months. At 6 month, he was detected to have grade 1/2 bilateral pleural effusion and was managed with drug interruption and oral dexamethasone with no significant reduction of fluid. CBC was normal. Dasatinib was continued. At one year, he lost cytognetic response with emergence of complex karyotype and medullary lymphoid blast crisis was confirmed. Pleural fluid showed lymphoblasts proven by cytology and immunophenotype. He received vincristine and prednisone followed by a change to imatinib. His disease progressed further and died at 2 years from diagnosis.
A 39 yr old male with molecular relapse and M244V Abl Kd mutation at 8 years since diagnosis and 6.5 yrs on imatinib 400–800 mg daily was offered dasatinib 100 mg OD. After 24 months, he developed grade2 left pleural effusion which responded poorly to drug interruption, therapeutic tapping and prednisone. A few months later he developed constitutional symptoms and CT chest, bronchoscopy/BAL proved to have left lung tuberculosis. Currently, he is responding favorably to anti-tubercular therapy. He was switched back to imatinib and remains in cytogenetic remission.
A 21 yr old male with cytogenetic non-responder to imatinib 800 mg daily was put on dasatinib 100 mg OD. An MMR was achieved. He developed left pleural effusion after 4 years of dasatinib. Extensive investigation for any specific pathology was not productive. He was put on empiric anti-tubercular therapy with no response. It is being treated as a dasatinib induced effusion.
During dasatinib therapy, the causes of pleural effusions could be varied – drug related, extramedullary blast crisis or tubercular. Radiological, cytological and microbiological investigations could be indicated after careful clinical evaluation.
Saikia:Bristol -Myers Squibb: Research Funding, Speakers Bureau.
Posterior reversible encephalopathy syndrome (PRES), is a syndrome characterized by headache, confusion, seizures and visual loss, which was first described in 1996 by Judy Hinchey. The cause of PRES ...is not yet understood. We report a case of a 50-year-old man that developed PRES after the use of mFOLFOX 6 (Oxaliplatin/5-Fluoracil/Leucovorin) chemotherapy for colorectal cancer.
An adult patient of colorectal cancer underwent resection of the primary tumor followed by adjuvant chemotherapy with mFOLFOX 6. Five days after the eleventh cycle he presented with headache and ataxia. A brain MRI (FLAIR/T2) was performed the same day which showed an increase of signal in both cerebellar lobes. Diagnosis of PRES was made by the radiologist. His symptoms started to improve after 3 days of hospitalization, and he was discharged after five days of hospital stay. A repeat MRI after 2 weeks revealed complete resolution of the hyper intense lesions in bilateral cerebellar lobes.
Oncologists must be aware of this uncommon but specific adverse effect of FOLFOX chemotherapy, as prompt diagnosis may result in complete resolution of PRES.
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