Adjuvant Gemcitabine Plus Cisplatin and Chemoradiation in Patients With Gallbladder Cancer: A Randomized Clinical Trial.

Importance: There is limited evidence with regard to the benefit of adjuvant chemotherapy chemoradiotherapy in resected gallbladder cancers (GBCs). Objective: To establish a baseline survival rate for operated GBCs in patients receiving either gemcitabine plus cisplatin (GC) or capecitabine and capecitabine concurrent with chemoradiation (CCRT). Design, Setting, and Participants: The GECCOR-GB study was a multicenter, open-label, randomized phase 2 noncomparator "pick the winner" design trial of adjuvant GC and CCRT in patients with resected histologically confirmed adenocarcinoma or adenosquamous carcinoma of the gallbladder, (stage II/III) with no local residual tumor (R0) or microscopic residual tumor (R1). The study was carried out in 3 tertiary cancer institutions in India. Patients 18 years or older with adequate end-organ functions, and Eastern Cooperative Oncology Group Performance Status of 1 or lower between May 2019 and February 2022 were enrolled. The cutoff date for data analysis was February 28, 2023. Interventions: Patients were randomized 1:1 to receive either GC every 3 weeks (maximum of 6 cycles) or CCRT comprising capecitabine with concurrent chemoradiation (capecitabine concurrent with radiotherapy) sandwiched between capecitabine chemotherapy. Main Outcomes and Measures: The primary outcome was disease-free survival (DFS) at 1 year in randomized patients. This study was conducted as 2 parallel, single-stage phase 2 clinical trials. Within each treatment arm, a 1-year DFS rate of less than 59% was considered as insufficient activity, whereas a 1-year DFS rate of 77% or higher would be considered as sufficient activity. Results: With a median follow-up of 23 months, 90 patients were randomized, 45 in each arm. Overall, there were 31 women (69%) and 14 men (31%) in the GC arm with a mean (range) age of 56 (33-72) years and 34 women (76%) and 11 men (24%) in the CCRT group with a mean (range) age of 55 (26-69) years. In the GC and CCRT arms, 1-year DFS and estimated 2-year DFS was 88.9% (95% CI, 79.5-98.3) and 74.8% (95% CI, 60.4-89.2), and 77.8% (95% CI, 65.4-90.2) and 74.8% (95% CI, 59.9-86.3), respectively. Completion rates for planned treatment was 82% in the GC arm and 62% in the CCRT arm. Conclusions and Relevance: In this randomized clinical trial, GC and CCRT crossed the prespecified trial end points of 1-year DFS in patients with resected stage II/III GBCs. The results set a baseline for a larger phase 3 trial evaluating both regimens in operated GBCs. Trial Registration: ClinicalTrials.gov Identifier: CTRI/2019/05/019323I.

A Clinicopathological Analysis of Molecular Subtypes of Breast Cancer using Immunohistochemical Surrogates: A 6-Year Institutional Experience from a Tertiary Cancer Center in North India.

Puneet Kaur SomalObjective Classification of breast cancer into different molecular subtypes has important prognostic and therapeutic implications. The immunohistochemistry surrogate classification has been advocated for this purpose. The primary objective of the present study was to assess the prevalence of the different molecular subtypes of invasive breast carcinoma and study the clinicopathological parameters in a tertiary care cancer center in rural North India. Materials and Methods All female patients diagnosed with invasive breast cancer and registered between January 1, 2015, and December 31, 2020, were included. Patients with bilateral cancer, missing information on HER2/ER/PR receptor status, absence of reflex FISH testing after an equivocal score on Her 2 IHC were excluded. The tumors were classified into different molecular subtypes based on IHC expression as follows-luminal A-like (ER- and PR-positive, Her2-negative, Ki67 < 20%), luminal B-like Her2-negative (ER-positive, Her2-negative and any one of the following Ki67% ≥ 20% or PR-negative/low, luminal B-like Her2-positive (ER- and HER2-positive, any Ki67, any PR), Her2-positive (ER- and PR-negative, Her2-positive) and TNBC (ER, PR, Her2-negative). Chi square test was used to compare the clinicopathological parameters between these subtypes. Results A total of 1,625 cases were included. Luminal B-like subtype was the most common (41.72%). The proportion of each subtype was luminal A (15.69%), luminal B Her2-negative (23.93%), luminal B Her2-positive (17.78%), Her2-positive (15.26%), TNBC (27.32%). Majority of the tumors were Grade 3 (75.81%). Nodal metastases were present in 59%. On subanalysis of the luminal type tumors without Her2 expression (luminal A-like and luminal B-like (Her2-negative), luminal A-like tumors presented significantly with a lower grade ( p < 0.001) and more frequent node-negative disease in comparison to luminal B-like (Her2-negative) tumors. In comparison to other subtypes, TNBC tumors were more frequently seen in the premenopausal age group ( p < 0.001) and presented with node-negative disease ( p < 0.001). Conclusion This is one of the largest studies that enumerates the prevalence of various molecular subtypes of breast cancer in North India. Luminal B-like tumors were the most common followed by TNBC. TNBC tumors presented more commonly in premenopausal age group and with node negative disease in comparison to other subtypes.

Overall survival of prostate cancer from Sangrur and Mansa cancer registries of Punjab state, India.

Introduction: There is a scarcity of population-based prostate cancer survival data in India. We assessed the population-based, overall survival of patients with prostate cancer from the Sangrur and Mansa cancer registries of the Punjab state, India. Methods: In the year 2013-2016, a total of 171 prostate cancer cases were registered in these two registries. Based on these registries, survival analysis was performed using the date of diagnosis as the starting date and the last follow-up date being December 31, 2021 or the date of death. Survival was calculated using STATA software. Relative survival was calculated using the Pohar Perme method. Results: Follow up was available for all the registered cases. Of the 171 cases, 41 (24%) were alive and 130 (76.0%) were dead. Of the prescribed treatments, 106 (62.7%) cases completed the treatment and 63 (37.3%) cases did not complete the treatment. Overall, 5-year age-standardized prostate cancer relative survival was 30.3%. Patients who completed the treatment had a 7.8 times higher 5-year relative survival (45.5%) compared to those who did not (5.8%). The difference between the two groups is statistically significant (hazard ratio 0.16, 95% confidence interval [0.10-0.27]). Conclusion: To improve survival, we need to raise awareness in the community and among primary physicians so that prostate cancer cases can reach the hospital early and should be treated effectively. The cancer center should develop the systems in their hospital so that there will be no hurdles to the patients in treatment completion. We found a low overall relative survival among patients of prostate cancer in these two registries. Patients who received treatment had a significantly higher survival.

Challenges Encountered and Pattern-Based Analysis of Bone Marrow Biopsy in Lymphomas: An Institutional Experience.

Objective The evaluation of bone marrow (BM) status is an integral part of the initial workup of patients diagnosed with lymphoma as it plays an important role in staging and predicting prognosis in these patients. This article determines the incidence and pattern of BM involvement in lymphoma cases and distinguishes benign from malignant lymphoid aggregates in BM biopsies. Materials and Methods The study group included 121 cases of Hodgkin and non-Hodgkin lymphomas for which BM biopsies were performed, fixed in acetic acid-zinc formalin solution, decalcified using 10% formic acid, and subjected to hematoxylin and eosin and immunohistochemistry. Results The overall incidence of BM biopsy involvement in our study was 31.4% (37/118), including 34.7% (35/101) in cases of B cell lymphomas, 25% (2/8) in cases of T cell lymphomas, and no involvement in Hodgkin lymphoma. The predominant histological pattern of BM involvement was diffused (14/37; 37.8%), followed by interstitial (10/37; 27.1%). Five cases revealed benign nonparatrabecular lymphoid aggregates which could be confused with lymphomatous involvement, especially in low grade lymphomas. Conclusion A careful examination of the BM biopsies along with clinical history, peripheral blood examination, flow cytometry, and immunohistochemistry will help in arriving at the correct diagnosis.

Recurrence pattern with respect to two different dose fractionations in patients with locally advanced head and neck cancer treated with chemoradiation using image-guided volumetric arc therapy.

BACKGROUND: Patients with head and neck cancer were treated with either 70 Gy in 35 fractions (Arm A) or 66 Gy in 30 fractions (Arm B). MATERIALS AND METHODS: Total 168 patients of carcinoma oropharynx, larynx, and hypopharynx treated with radical chemoradiation in two Arm A versus B (65 vs. 103 patients). RESULTS: With a median follow-up of 16 months (0-67), 2 year disease-free survival (DFS) and overall survival (OS) was 56.3% versus 62.1% (p = 0.64) and 44.5% versus 53.0% (p = 0.51) in Arm A versus B. Total 22 (33.8%) versus 28 (27.2%) failed locoregionally. Majority of failures were infield for both primary (17 vs. 23 cases) and nodes (13 vs. 12) in Arm A versus B. Ten (71.4%) vs. 10 (76.9%) had nodal failure in index nodal level only. CONCLUSION: Commonly seen failure in head-neck radical chemoradiation is within infield high-risk volume, nodal failure being most common in index nodal level.

A comparative evaluation of diffuse reflectance and Raman spectroscopy in the detection of cervical cancer.

Optical spectroscopic techniques show improved diagnostic accuracy for non-invasive detection of cervical cancers. In this study, sensitivity and specificity of two in vivo modalities, i.e diffuse reflectance spectroscopy (DRS) and Raman spectroscopy (RS), were compared by utilizing spectra recorded from the same sites (67 tumor (T), 22 normal cervix (C), and 57 normal vagina (V)). Data was analysed using principal component - linear discriminant analysis (PC-LDA), and validated using leave-one-out-cross-validation (LOOCV). Sensitivity, specificity, positive predictive value and negative predictive value for classification between normal (N) and tumor (T) sites were 91%, 96%, 95% and 93%, respectively for RS and 85%, 95%, 93% and 88%, respectively for DRS. Even though DRS revealed slightly lower diagnostic accuracies, owing to its lower cost and portability, it was found to be more suited for cervical cancer screening in low resource settings. On the other hand, RS based devices could be ideal for screening patients with centralised facilities in developing countries.

In vivo Raman spectroscopy of human uterine cervix: exploring the utility of vagina as an internal control.

In vivo Raman spectroscopy is being projected as a new, noninvasive method for cervical cancer diagnosis. In most of the reported studies, normal areas in the cancerous cervix were used as control. However, in the Indian subcontinent, the majority of cervical cancers are detected at advanced stages, leaving no normal sites for acquiring control spectra. Moreover, vagina and ectocervix are reported to have similar biochemical composition. Thus, in the present study, we have evaluated the feasibility of classifying normal and cancerous conditions in the Indian population and we have also explored the utility of the vagina as an internal control. A total of 228 normal and 181 tumor in vivo Raman spectra were acquired from 93 subjects under clinical supervision. The spectral features in normal conditions suggest the presence of collagen, while DNA and noncollagenous proteins were abundant in tumors. Principal-component linear discriminant analysis (PC-LDA) yielded 97% classification efficiency between normal and tumor groups. An analysis of a normal cervix and vaginal controls of cancerous and noncancerous subjects suggests similar spectral features between these groups. PC-LDA of tumor, normal cervix, and vaginal controls further support the utility of the vagina as an internal control. Overall, findings of the study corroborate with earlier studies and facilitate objective, noninvasive, and rapid Raman spectroscopic-based screening/diagnosis of cervical cancers.

Contribution of hot spring bacterial consortium in cadmium and lead bioremediation through quadratic programming model.

In the present investigation, a number of experiments have been conducted to isolate microbial strains from Taptapani Hot Spring Odisha, India for bioremediation of cadmium and lead. The strains Stenotrophomonas maltophilia (SS1), Aeromonas veronii (SS2) and Bacillus barbaricus (SS3) have shown better adaptation to metal tolerance test, with different concentrations of cadmium and lead and hence have been selected for further studies of metal microbial interaction and optimization. The results of bioremediation process indicate that consortium of thermophilic isolates adsorbed heavy metals more effectively than the individually treated isolates. Therefore, A 24 full factorial central composite design has been employed to analyze the effect of metal ion concentration, microbial concentration and time on removal of heavy metals with consortium. Analysis of variance (ANOVA) shows a high coefficient of determination value. The kinetic data have been fitted to pseudo-first order and second-order models. The isotherm equilibrium data have been well fitted by the Langmuir and Freundlich models. The optimum removal conditions determined for initial ion concentration was 0.3g/l; contact time 72h; microbial concentration, 3ml/l; and pH 7. At optimum adsorption conditions, the adsorption of cadmium and lead are found to be 92% and 93%, respectively, and presence of metals was confirmed through EDS analysis.