Abstract
The combination of cyclin dependent kinase 4/6 inhibitors with endocrine therapy is the standard therapy in hormone receptor positive HER-2 negative metastatic breast cancer (HR+/HER2− MBC). ...Several randomized trials have shown the benefits of this combination, however, real world evidence in the Indian patients is warranted. The present study reports the largest real world multicentric data from Indian population on the use of Palbociclib in HR+/HER2− MBC. A multicentric study on the HR+/HER2− MBC patients who received palbociclib with hormonal agent (Aromatase inhibitors/Fulvestrant) between February 2017 and May 2020 was conducted. Clinical and demographic information and survival data was retrieved from the Hospital medical records. Among a total of 188 patients, 57% patients were premenopausal and 17% patients had bone only disease. Altogether, 115 (61%) patients received palbociclib with Aromatase inhibitors in the first line whereas 73 (39%) patients received it in the second line with Fulvestrant. The median follow up period with advanced disease was 13 months. The median progression free survival in the first line and second line was 20.2 months and 12 months, respectively (
p
-value < 0.0001). The objective response rate was 80% and 47.9% in first and second lines, respectively. Dose interruptions/ discontinuation were done in 14.9% and 2.7% patients in the first and second lines, respectively. In terms of toxicity, 10% patients had grade 3–4 adverse events. The present real world data of the use of palbociclib in Indian population suggests similar effectiveness to previously published real world evidences and has been adapted as the standard of care in the first and second line treatment of HR+/HER2− MBC.
Non-small cell lung cancer (NSCLC) has emerged as the poster child of molecular medicine. Kirsten rat sarcoma (KRAS)-mutated NSCLC is a common yet heterogeneous entity with distinct clinical and ...prognostic characteristics. Therapeutically, targeting the KRAS mutation in NSCLC has been the most difficult challenge faced by scientists and drug developers and after decades of efforts, a final breakthrough in the form of KRAS G12C inhibitors has emerged. In this edition of the biomarker series, we review KRAS, its biology, clinical features, and the therapeutic options in KRAS-mutant NSCLC. We performed a thorough search in PubMed, Embase, and Scopus and finally included 59 articles to write this review.
The present analysis reports the clinical, pathological, treatment profile and overall survival (OS) and disease-free survival (DFS) outcomes of consecutive breast cancer patients from three Indian ...centres, who underwent curative surgery as their first treatment. Among the 3453 patients, stage I, II, and III cases were 11.75%, 66.79%, and 21.64%, respectively while hormone receptor positive/HER2 negative, triple negative (TNBC) and hormone receptor any/HER2 positive cases were 55.2%, 24.2% and 20.6%, respectively. The five-year OS in the entire cohort, node-negative and node-positive patients were 94.1% (93.25-94.98), 96.17% (95.2-97.15) and 91.83% (90.36-93.31), respectively, and the corresponding DFS were 88.1% (86.96-89.31), 92.0% (90.64-93.39) and 83.93% (82.03-85.89), respectively. The five-year OS in hormone receptor positive/HER2 negative, TNBC and HER2 subgroups were 96.11% (95.12-97.1), 92.74% (90.73-94.8) and 90.62% (88.17-93.15), respectively, and the corresponding DFS were 91.59% (90.19-93.02), 85.46% (82.79-88.22) and 81.29% (78.11-84.61), respectively. This is the largest dataset of early breast cancer patients from India with survival outcome analysis and can therefore serve as a benchmark for future studies.
To investigate Ki-67 index with regard to its ability to predict achievement of pathologic complete response (pCR) to neoadjuvant chemotherapy (NACT) in breast cancer patient.
It was a prospective ...observational study, conducted in Department of Medical Oncology, Rajiv Gandhi Cancer Institute & Research Center (RGCIRC), New Delhi from February 2014 to March 2016. A total of 134 patients with Stage II/III breast cancer who underwent NACT followed by surgery at our center were enrolled and analyzed. Before starting the treatment, clinical, tumor-related and treatment-related factors were recorded. Response evaluation was done clinically and radiologically after completion of NACT and pathologically on the surgical specimen. We calculated Ki-67 cut-off of 35% to label it as high by area under Receiver operating characteristic curve analysis for prediction of pCR.
Clinical complete response (cCR) was observed in 35/134 (26.1%) patients while pCR was observed in 32/134 (23.9%) patients. On univariate analysis, higher grade (III), high Ki-67 index (>35%) and number of chemotherapy cycles (>3) were associated with better CCR rates. On multivariate analysis, number of chemotherapy cycles (>3) and high Ki-67 index (>35%) were independent predictive factors. For the predictive factors of pCR, univariate analysis showed grade (III), estrogen receptor/progesterone receptor negativity, HER-2 positivity, number of chemotherapy cycles (>3), TNBC and high Ki-67 index (>35%) to be associated with higher pCR rates. On multivariate analysis, Ki-67 index >35% and HER-2 positivity were the only independent predictive factors of pCR.
We suggest 35% as best cut-off for Ki-67 expression for predicting response to NACT and achievement of pCR. Validation of this cut-off is required in larger studies.
Anaplastic lymphoma kinase (ALK) rearranged non-small-cell lung cancer (NSCLC) comprises a distinct molecular entity with a reported global prevalence of 5-7%. The development and rapid approvals of ...small molecule ALK tyrosine kinase inhibitors (TKIs) have led to the development of diagnostic strategies with robust methodology and superior attributes. Owing to myriad alterations which can be present in the ALK gene in NSCLC, it is important to understand the principal attributes as well as limitations of each to aid in optimal therapeutic decision making. To prepare this review, we used the keywords, "ALK detection," "ALK NGS," "ALK TKI," and "EML4 (echinoderm microtubule-associated protein-like 4)-ALK," to search within scientific databases like Scopus, PubMed, and Embase. We chose 55 articles that we identified from this search. Detection of ALK is an essential frontline diagnostic test as per all international and national recommendations. The various modalities available include immunohistochemistry, fluorescence in situ hybridization, reverse transcriptase polymerase chain reaction, and DNA/RNA-based next-generation sequencing. Each has its own advantages and limitations with respect to test metrics like sensitivity and specificity, as well as ease of use, availability, and cost. This is a detailed review of these various techniques and their attributes.
Background
Angiosarcoma is an uncommon and highly aggressive malignant tumor. Angiosarcoma presenting as diffuse alveolar hemorrhage (DAH) is rare.
Case presentation
A young female who presented with ...history of dyspnea was found to have features of DAH on radiological evaluation. Angiosarcoma was confirmed from the histopathological examination of the underlying lung nodule. Management with the palliative chemotherapy showed clinical improvement, and resolution of changes of DAH on imaging.
Conclusion
Angiosarcomas are not usually listed in the causes of DAH. It must be considered in the differentials of DAH after ruling out the common causes.
Anaplastic lymphoma kinase (ALK) rearranged NSCLC comprises a molecularly distinct subgroup occurring in 10% cases. Various EML4–ALK and non EML4 variants are known to occur which can be detected ...only on NGS and show differential TKI responses. 113 ALK-IHC positive cases were subjected to a custom panel-based NGS for detection of ALK variants. Clinicopathologic features and outcomes were studied and propensity-matched analysis was done. The median age of the overall cohort was 53 years. 91 (80.5%) cases were NGS positive, the most common being EML4–ALK (90, 98.9%) cases. The most common EML4 variant was Variant 1 (40, 35%) cases, Variant 3 (28, 25%) cases, and Variant 2 (17, 15%) cases. One novel EML4–ALK variant was also encountered which was found to be intrinsically resistant to crizotinib. On pre-weight-adjusted comparison, Variant 1 group had a higher occurrence of brain and extrathoracic metastases. The median OS was 44 months for the entire cohort. 49 patients received crizotinib as first-line TKI. Among these, the median OS for Variant 2 was not reached; it was 38 months and 24 months for Variant 1 and Variant 3, respectively. The median PFS for crizotinib treated patients was 8.3 months (Variant 2: 11 months, Variant 1: 8 months, and Variant 3: 9 months). On propensity-matched analyses, there was no difference in OS and PFS between Variant 1 and Variant 3, with higher HR for Variant 3. We present a large data set evaluating clinical and outcome differences between ALK variants. The unique standpoint of this study involves the propensity-weighted model to account for differences among the groups, with no prognostic differences between Variant 1 and Variant 3, which is distinct from literature.
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