Real-World Data on Treatment Outcome of ALK-Positive Non-Small Cell Lung Cancer from an Indian Multicentric Cancer Registry.

Lalatendu Moharana The Anaplastic lymphoma kinase inhibitors (ALKi) represent the standard of care for metastatic non-small cell lung cancer (NSCLC) patients with EML4-ALK rearrangements. Various ALKi agents are available; however, not all eligible patients receive treatment with them due to various reasons. Given the limited real-world data available in our country, we aimed to assess treatment outcomes through a multicenter collaboration. This retrospective, multi-institutional study was conducted under the Network of Oncology Clinical Trials India and included a total of 67 ALK-positive metastatic lung cancer patients from 10 institutes across India, with a median follow-up of 23 months. In the first line setting, the objective response rate (ORR) with ALKi was 63.6% (crizotinib: 60.7%, ceritinib: 70%, alectinib: 66.6%, p = 0.508), while with chemotherapy, it was 26.1%. The median progression-free survival (mPFS) for the first line ALKi group was significantly higher than that for chemotherapy (19 vs. 9 months, p = 0.00, hazard ratio [HR] = 0.30, 95% confidence interval [CI]: 0.17-0.54). The mPFS for crizotinib, alectinib, and ceritinib was 17, 22, and 19 months, respectively ( p = 0.48). Patients who received ALKi upfront or after 1 to 3 cycles of chemotherapy or after 4 or more cycles of chemotherapy had mPFS of 16, 22, and 23 months, respectively ( p = 0.47). ALKi showed superior mPFS compared to chemotherapy in the second line (14 vs. 5 months; p = 0.002) and the third line (20 vs. 4 months; p = 0.009). The median overall survival (OS) was significantly better in patients who received ALKi in any line of therapy (44 vs. 14 months, p < 0.001, HR = 0.10, 95% CI: 0.04-0.23). Brain progression was higher among those who did not receive ALKi (69.2 vs. 31.5%). In conclusion, the use of ALKi as first line treatment for ALK-positive metastatic NSCLC patients resulted in improved PFS. PFS and ORR did not significantly differ between patients who received ALKi upfront or after initiating chemotherapy. Notably, patients who received ALKi in second or later lines demonstrated significantly better outcomes compared to those receiving chemotherapy. The use of ALKi in any line of therapy was associated with significantly prolonged OS.

Adolescent and Young Adults with Gastric Cancer (AYA-GC)-The Dilemma of an Under-Represented Group: A Multi-Institutional Analysis from the Indian Subcontinent.

Soumya Surath PandaGastric cancer (GC) is often ignored at a young age, which frequently leads to tragic consequences. The worldwide incidence of GC is increasing at a young age. In view of the limited Indian publication, we sought to characterize clinicopathological parameters and risk factors in the adolescents and young adults (AYA) population. Retrospective data from six centers (which are part of the Network of Oncology Clinical Trials in India) from 2015 to 2020 were collected from patient (18-39 years of age) records. This study was approved by the institutional ethical committee of individual centers. All statistical analyses were performed using Microsoft Excel and SPSS (Version 20). Data interpretation along with the analysis of obtained results was carried out using the following tests: Qualitative data was expressed in terms of frequency/percentage. One-hundred fifty-two AYA GC patients were enrolled. The 31 to 39 years age group was most affected in which 76.3% were females. The majority of patients were nonalcoholic (93.4%), nonsmokers (98.0%), and without a family history (98.0%). The most common (MC) presenting symptom was abdominal pain (67.1%). MC site was antrum (48%). Among esophagogastric junction cancers, the majority were type I and II Siewert classifications (77% [20/26] patients in cardia), MC histology-signet ring cell (67.1%) followed by diffuse-type (65.1%). Most were poorly differentiated (65.1%) and were diagnosed at an advanced stage (III & IV= 54.6%). This is one of our country's first large multicenter studies on GC in the AYA population. There was a higher female prevalence, aggressive tumor behavior and the majority of patients were diagnosed at a more advanced stage. The majority were nonsmokers with a negative family history. Awareness among general people, researchers, clinicians, and policymakers must be improved to better the loss of life years in the younger population.

PD-L1 expression in head and neck squamous cell carcinoma and its clinical significance: A prospective observational study from a tertiary care centre.

BACKGROUND: Programmed Death Ligand 1 (PD-L1) expression in tumor cells contribute to tumor immunity and therapies directed against it, have shown encouraging results in recent years. As there is limited data on the significance of PD-L1 expression in Head and Neck Squamous Cell Carcinoma (HNSCC) from India, we aimed to study the PD-L1 expression and its relation with different clinic-pathological parameters in patients of HNSCC from a tertiary care center in Eastern India. METHODS: A prospective evaluation of HNSCC patients diagnosed and managed at our center over a period of two and half years, was performed. PD-L1 expression in formalin fixed-paraffin embedded tumor tissue specimens was measured using SP-263 (Ventana) and 22C3 (Dako). A PD-L1 expression of <1%, 1-19%, ≥20% were considered negative, low, and high expression, respectively, and was correlated with various parameters. RESULTS: A total of 71 patients (mean age 50.8 ± 13.3 years, 86% males) were diagnosed with HNSCC (buccal mucosa-28, tongue-22, rest of oral cavity-8, larynx-7, nasopharynx-6). The tumor was poorly differentiated in 12 (17%). PD-L1 positivity was seen in a total of 51 (71.8%) patients (1-19%:18, ≥20%:33). Thirty (85.7%) patients among those aged <50 years and 58.3% of those aged ≥50 years showed PD-L1 positivity which was significant (P = 0.01). There were no statistically significant differences in PD-L1 positivity with respect to gender, tobacco use, tumor grade as well as tumor and nodal stage. Median follow up duration was 18 months (range 3-31 months) and there was significant difference in overall survival among PD-L1 positive and negative groups (31 vs 24 months; log rank P = 0.03). CONCLUSIONS: 72% of HNSCC patients in our cohort showed PD-L1 positivity and it was not associated with any patient demographic characteristics or aggressive pathological features. Positive PD-L1 expression may have a beneficial effect on overall survival in HNSCC.

PD-L1 expression and its significance in advanced NSCLC: real-world experience from a tertiary care center.

BACKGROUND: Targeted therapies against programmed death ligand-1 (PD-L1) in non-small cell lung cancer (NSCLC) have revolutionized the management in recent years. There is paucity of data on the significance of PD-L1 expression in NSCLC from India. We aimed to study the prevalence of PD-L1 expression and its relation with different clinico-pathological parameters in advanced NSCLC from a tertiary care center in Eastern India. METHODS: All consecutive patients with advanced NSCLC diagnosed from January 2020 to December 2021 were prospectively evaluated for PD-L1 expression in formalin fixed-paraffin embedded tumor tissue specimens using immunohistochemistry analysis. A PD-L1 expression of < 1%, 1-49%, and ≥ 50% were considered negative, low, and high expression positive respectively, and association with various parameters was performed. RESULTS: Out of the 94 patients (mean age 59.6 ± 14 years and 63.8% males), PD-L1 positivity was seen in 42 (44.7%) patients, with low positivity (1-49%) in 29 patients and high positivity (≥ 50%) in 13 patients. Epidermal Growth Factor Receptor (EGFR) mutations were seen in 28 patients (29.8%). There were no significant differences in PD-L1 positivity with respect to gender, age, and molecular mutation status. PD-L1 positivity was significantly associated with tobacco use (p = 0.04), advanced tumor stage (p < 0.001), and higher nodal stage (p < 0.001). Median overall survival in the cohort was 17 months and it was not significantly different between the PD-L1 positive and negative groups. CONCLUSIONS: Forty-five percent of advanced NSCLC patients in our cohort showed positive PD-L1 expression and it is associated with tobacco use and aggressive tumor characteristics.

Comparison Between CHOP and DAEPOCH with or Without Rituximab in Adult High Grade B Cell Lymphoma, Not Otherwise Specified; A Retrospective Study From a Tertiary Cancer Hospital in South India.

Lymphoma that on morphology appear blastoid or intermediate between DLBCL and BL but who lack myc and bcl-2 and/or bcl-6 rearrangements are grouped under high grade B-cell lymphoma, not otherwise specified (HGBL, NOS). Only a few studies have yet compared the outcome of HGBL, NOS treated with different chemo-immunotherapy regimens. HGBL, NOS patients were analyzed retrospectively, who were treated with CHOP or DAEPOCH regimens every 21 days for six cycles with or without rituximab. The primary clinical objective was progression free survival. One and two year PFS rates were 29.4% and 20.6% for the CHOP arm and, 65.2% and 47.8% for the DAEPOCH arm respectively. There was statistically significant difference in mean PFS between the arms (DAEPOCH vs CHOP: 19.7 months vs 12.8 months; HR = 0.44, p = 0.02, 95% CI: 0.22-0.88). One and two year OS rates were 91.1% and 20.5% for the CHOP arm and 95.6% and 60.8% for the DAEPOCH arm respectively. Mean OS was significantly better for DAEPOCH arm (28.1 months vs 20.7 months: HR = 0.43, p = 0.03, 95% CI: 0.20-0.92). Grade 3 and 4 hematological and non-hematological toxicities were more common in DAEPOCH arm. There were 2 treatment related deaths, 1 in each arm (4.3% for DAEPOCH vs 2.9% for CHOP). HGBL, NOS is a heterogeneous group of aggressive lymphoma associated with early relapse in nearly half of the cases. Intensive regimens like DAEPOCH is associated with improved outcome in terms of PFS and OS. Though toxicities are more with DAEPOCH, they are manageable and treatment related mortality is low.

Cutaneous involvement in diffuse large B cell lymphoma at presentation: report of two rare cases and literature review.

BACKGROUND: Diffuse large B cell lymphoma (DLBCL) can occur at nodal and/or extra-nodal sites. After the gastrointestinal tract, cutaneous involvement predominates in extra-nodal DLBCL. Skin involvement at presentation can be in the form of plaques, papules, nodules or ulcers. Differentiating primary cutaneous DLBCL from systemic DLBCL with cutaneous involvement is important for appropriate patient management. CASE PRESENTATION: We describe here, two interesting cases of skin involvement in DLBCL- one primary cutaneous DLBCL and the other, cutaneous involvement in systemic DLBCL with different clinico-pathological profiles. Though both cases had almost similar morphology of the skin lesions (ulcero-proliferative) at presentation, the disease was confined to the skin in the former, while the latter had involvement of lymph nodes and bone marrow. CONCLUSIONS: Meticulous clinical evaluation, appropriate histopathological and immunohistochemical workup helped in their diagnosis and correct classification of the disease status, guiding the further treatment decisions.