Outcome in patients of hormone receptor (HR) positive (Her 2) negative metastatic breast cancer treated with palbociclib – A real-world experience

Objectives: We present real-world outcome with the use of palbociclib in patients with HR-positive Her2-negative breast cancer treated at single center in India. Material and Methods: We conducted a medical audit of consecutive patients with HR-positive Her2-negative metastatic breast cancer, who were treated with palbociclib at our center between November 2016 and May 2020. Palbociclib was commenced at a dose of 125 mg orally once daily and a schedule of 21 days on therapy followed by 7 days off therapy was followed. Survival analysis included the Kaplan–Meier method using Statistical Package for the Social Sciences software (Version 26). HRs were calculated using Cox proportional hazard regression models and 95% confidence intervals (CIs) for the incidence estimates. Results: A total of 67 female patients were commenced on treatment with palbociclib between November 2016 and May 2020. The median age was 55 years (range 29–78 years). A total of 51 (76%) of these patients were postmenopausal and the remaining 16 were premenopausal. Baseline metastatic disease involved one organ/site in 23 (34%), two organs/sites in 32 (48%), three or more in 12 (18%). Bony metastasis alone was seen in 17 (25%) patients, visceral alone in 30 (45%), and the remaining 20 had both bony and visceral metastases. For these 67 patients, palbociclib was commenced as 1st line systemic therapy in 24 (36%) cases. Amongst the remaining 43 cases, it was 2nd line in 21 (31%); 3rd line and beyond in 22 (33%). Median PFS was 16.1 months (95% CI: 9.6–22.8) and median OS was 20.7 months (95% CI: 14.1–27.3). Median PFS for palbociclib use in first line was 18.7 months (95% CI: 4.6–32.9) while in subsequent lines, it was 13.8 months (95% CI: 9.8–17.9; log-rank P = 0.228). Median OS in patients who received palbociclib in first line was 23.2 months (95 % CI 20.1–26.3) and for those why received it in subsequent lines was 16.3 months (95 % CI: 12.5–20.1; P = 0.069). In total population, best response on imaging was CR in 11 (16%) cases (06 in 1st line setting and 05 in subsequent line setting); PR in 33 (49%); SD in 03; and progressive disease in 20. Median PFS with bone only metastasis: 20.9 months (95 % CI: 5.9–36.0), while with visceral metastasis 16.1 months (95% CI: 9.8–22.5; P = 0.537). Median OS with bone only metastasis: 22.7 months (95% CI: 17.8–27.5), while with visceral metastasis, it was 18.5 months (95% CI: 13.6–23.4; P = 0.314). Conclusion: Palbociclib is a useful addition in the management of HR +ve Her2 –ve breast cancer patients. Its benefit is confirmed in our real-world setting, both in the first and subsequent lines of therapy and the data are on similar lines as the global real-world data on palbociclib effectiveness.

Unusual presentation of an Epstein barr virus-negative extranodal natural killer/T cell lymphoma: A diagnostic dilemma

Extra-nodal Natural killer/T cell lymphoma (ENKTL) is a well-defined and highly aggressive form of NonHodgkin’s lymphoma with a scarcity of cases reported in literature. The most common primary site of involvement is the nasal cavity followed by skin and the gastrointestinal tract (GIT). Cutaneous involvement is a rarity. More than 95% of cases are usually in association with Epstein Barr Virus (EBV) infection. EBV negative ENKTL can be similar in clinical, pathological, and prognostic characteristics with EBV positive ENKTL. This malignancy is usually characterized by its poor prognosis irrespective of clinical stage and therapy. We describe here, a 58-year-old man presenting with multiple nodular lesions over legs and trunk, had an ileal perforation later, and was diagnosed as ENKTL on the ileal biopsy specimen. This case is being reported in view of the fulminant clinical course of the disease, simultaneous involvement of the GIT and skin without nasal or midline involvement, the usefulness of immunohistochemistry in arriving at a diagnosis, and EBV negativity which is quite rare in the Asian population.

Dual driver in non-small cell lung carcinoma – therapeutic dilemma

The presence of a targetable driver mutation in advanced non-small cell carcinoma is seen in about 40–50% of patients. The most common targetable driver identified is the mutation of the epidermal growth factor receptor gene. Conventionally, it was thought that these driver mutations of mutually exclusive. But due to the availability of a wider panel of molecular testing and highly sensitive methods of testing, there have been multiple case reports of more than one driver being identified in a single patient. Here in this series, we have described five such cases and have discussed the possible hypothesis and strategies in treatment.

Bioactive lipid: A novel diagnostic approach for retinoblastoma in clinical management

Bioactive lipids, presumably lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P), play a critical role in regulating an array of cellular functions ranging from cellular fate determination, inflammation, immunity, and cancer. Epidemiological evidence suggests that both the metabolites play a prominent role in the development and progression of oncogenic phenotype in a variety of cancers including breast, colorectal, pancreatic, and lymphoma. Previous studies have demonstrated the possible association of LPA, S1P and their receptor in regulating the pathogenesis of retinoblastoma, however, the exact mechanism involved in this event has not been studied in detail. Importantly, understating the mechanistic basis of LPA and S1P regulation is of utmost significance, as far the phenotypical complexity of retinoblastoma (RB) is concerned. Findings from the recent investigations elucidate the prospective role of S1P in provoking the chemoresistant behavior of RB cells for etoposide. In this context, the current paper will enable the identification of novel diagnostic biomarkers and therapeutic targets for better treatment and clinical efficacy in children with RB.

Post-chemotherapy maintenance treatment by nicotinamide riboside, a poly ADP ribose polymerase 1 inhibitor, in BRCA mutated advanced ovarian cancer – A perspective

Poly ADP ribose polymerase 1 (PARP-1) inhibitors are approved for post-chemotherapy maintenance in BRCA mutated ovarian carcinoma. Various PARP-1 inhibitors such as olaparib, rucaparib, niraparib, and veliparib are approved for this indication. These PARP-1 inhibitors are costly as well as having toxic potential, anemia, and neutropenia is the major side effects. Most of the middle-aged women in Indian subcontinent are anemic and prescription of PARP-1 inhibitors is tricky in such conditions, besides their cost is at times unaffordable as maintenance chemotherapy. Hence, we need an affordable yet lesser toxic PARP-1 inhibitor to solve this problem. Nicotinamide, a vitamin B3 amide can be re-purposed as PARP-1 inhibitor. Nicotinamide, albeit at a higher dose, can be efficacious as well as economical in its use as maintenance chemotherapy. It has toxic potential but the toxicity is both rare and manageable. We need a clinical trial for this purpose. Following perspective is on the current evidence on high dose nicotinamide and it is re-purposing as PARP-1 inhibitor.

Hyperthermic intraperitoneal chemotherapy in primary peritoneal cancer: Our experience in a young male

Primary peritoneal carcinomatosis (PPC) is a rare tumor, described in the literature almost exclusively in women. Patients with peritoneal carcinomatosis were considered incurable with low survival rates. This underwent a paradigm shift with hyperthermic intraperitoneal chemotherapy (HIPEC) after optimal cytoreductive surgery which changed the entire scenario. This case report describes the management of a 28-year-old male patient who was diagnosed to have PPC when he presented with massive ascites, who underwent cytoreductive surgery combined with HIPEC in our hospital. This procedure was complex for both the surgical team due to an extensive surgery, but also the anesthetist during the hyperthermic phase where the chemotherapy was administered. The post-operative recovery in such a case is also many times stormy and requires extreme vigilance. We had major challenges such as prolonged surgery, massive blood loss, temperature management, maintaining adequate urine output, and post-operative critical care. Extensive pre-operative preparation and proper coordination with the multidisciplinary team led us to handle the condition satisfactorily. The PPC in a young patient itself is a rare which enthuses us to report the case.