Squamous Histology Research Articles

A Phase II Basket Trial of Dual Anti-CTLA-4 and Anti-PD-1 Blockade in Rare Tumors (DART) SWOG S1609: Vulvar Cancers.

Dual PD-1/CTLA-4 inhibition shows promise in various malignancies. The SWOG S1609 DART trial presents initial results of ipilimumab/nivolumab in vulvar cancers. DART is a prospective/open-label/multicenter (1,016 US sites)/multi-cohort phase II clinical trial of ipilimumab (1mg/kg intravenously every 6 weeks) plus nivolumab (240mg intravenously every 2 weeks). The primary endpoint was objective response rate [ORR, confirmed complete and partial responses (CR and PR, respectively)] per RECISTv1.1; progression-free survival (PFS), overall survival (OS), clinical benefit rate [CBR; overall response plus stable disease (SD) ≥6 months], and toxicity are secondary endpoints. Sixteen evaluable patients (median age, 55.5 years; 0-6 prior therapies; no prior immunotherapy) were analyzed, all of whom had squamous cell carcinoma histology. ORR was 18.8% (3/16), CBR was 25% (4/16), and CBR plus unconfirmed PR rate was 31% (5/16); PFS was 34.1, 16.7. 15.5, 7.2 and 7.0 months for these five patients. The median PFS and OS were 2.2 and 7.6 months. The most common adverse events were diarrhea, fatigue, pruritus, anorexia, and nausea (25%, n=4 each). Grade 3-4 adverse events occurred in 25% of patients (n=4). There was 1 grade 1-2 adverse event (6.7%) that led to discontinuation, and 1 (6.7%) grade 5 death adverse event. Ipilimumab plus nivolumab in vulvar cancers resulted in an objective response in three out of 16 patients, all of whom had durable responses lasting over one year. Notably, two additional patients experienced durable SD and unconfirmed PR. Correlative studies to determine response and resistance markers are ongoing.

TROPION-Lung01 Results Indicate PFS Benefit With Datopotamab Deruxtecan Over Docetaxel in Previously Treated Nonsquamous NSCLC: A Critique and a Question

This commentary aims to point out how the results of the TROPION-LUNG01 study stress the "positive aspects" of the results, specifically, the increase in PFS, but hardly mention the potential harm to patients with squamous histology and lacks information on binary data (progression-free / progression, alive/death) as per CONSORT guidelines. Here, we also remark on the need for adherence to CONSORT guidelines to inform on the absolute and relative risks of Randomized Controlled Trials (RCT). We emphasize the need for further research to develop a framework of how oncologists might explain the differences between PFS and OS in simple terms for a lay audience to create a more thoughtful decision of patients to embark on any cancer treatment.

OGC SO03 - Impact of recent European consensus guidelines on Oligometastic Disease (OMD) and potential case load of Oesophagogastric cancer resections

Abstract Background To evaluate the impact of recently devised oligometastatic disease (OMD) criteria as per the European consensus guidelines on the eligibility of Oesophagogastric (OG) cancer patients for curative treatment. Method A retrospective analysis was conducted on OG cancer cases discussed at multidisciplinary team (MDT) meetings at a tertiary university hospital from January 2018 to December 2023. Inclusion criteria included T2-T4a adenocarcinomas, T2-T4b squamous cell carcinomas, small cell carcinoma and adeno-squamous carcinomas that were classified as M1 disease. Exclusion criteria were T4b adenocarcinomas, M1 peritoneal disease, non-adeno/ squamous carcinoma histology, M1 peritoneal cytology, and head and neck squamous cell carcinomas proximal to the thoracic inlet. Data on patient demographics, T stage, histology, and metastatic sites were analysed to identify those meeting the oligometastatic disease criteria. Results 483 of 696 were diagnosed as M1 disease. OMD was found in 59 cases (12.2%), with a median age of 72 years (43 males, 16 females). T stage distribution: 3 T2, 36 T3, 20 T4. Histology: 39 adenocarcinomas, 19 squamous cell carcinomas, 1 small cell carcinoma. Metastatic sites: non-regional lymph nodes (77.9%), liver (13.6%), lung (5.1%), bone (1.7%), adrenal (1.7%) Location of Lymph Node Involvement: 1Para-aortic11 (23.9%)2Right supra-clavicular7 (15.2%)3Porto-caval6 (13.0%)4Retro-crural5 (10.9%)5Upper mediastinal5 (10.9%)6Left Supraclavicular5 (10.9%)7Coeliac4 (8.6%)8SMA3 (6.6%) Conclusion Our data would suggest that 12.2% of patients discussed in the MDT may potentially be candidates for a curative intent treatment pathway. Although the long-term outcomes remain unclear, this approach may define a subgroup of patients who may benefit from curative intent treatment with the highest site being para-aortic nodes.

Durvalumab Following Chemoradiotherapy for Stage III Non-small Cell Lung Cancer: Differences in Survival Based on Age and Post-Progression Systemic Therapy.

Concurrent chemoradiotherapy (cCRT) followed by 1 year of the immune checkpoint inhibitor (ICI) durvalumab is standard of care for patients with unresectable stage III nonsmall cell lung cancer (NSCLC). The purpose of this study was to evaluate survival outcomes of (1) cCRT followed by durvalumab in patients older versus younger than 75 years of age and (2) post-progression treatment with ICI alone versus chemotherapy alone versus combined ICI and chemotherapy. Patients with unresectable stage III NSCLC treated between January 2018 and July 2023 with cCRT followed by durvalumab were identified retrospectively. Progression-free survival (PFS) and overall survival (OS) from ICI start were analyzed in three cohorts aged < 65, 65-74, and ≥ 75 years. Multivariable Cox proportional hazard regression modelling of factors associated with OS was undertaken. Logistic regression analysis identified risk factors of early durvalumab discontinuation for toxicity. Time from first salvage drug treatment to death (OS-2) was described. A total of 472 patients were analyzed: the proportions aged < 65, 65-74, and ≥ 75 years were 34.3%, 42.8%, and 22.9%, respectively. Odds of early durvalumab discontinuation was 2.2-fold greater in the oldest (versus youngest) cohort. Age associated differences in median PFS (26.7months, 20.3months, and 14.2months; p< 0.001) and OS (60.8months, 44.4 months, and 27.6 months; p< 0.001) were observed. On multivariable analysis, factors associated with shorter OS were age ≥ 75years (versus < 65), performance status 2/3 (versus 0/1), stage IIIC (versus IIIA), neutrophil to lymphocyte ratio (per 7.43 unit increase), Charlson comorbidity index (per 1 unit increase), tumoral PD-L1 expression < 1% (versus ≥ 50%, 1-49%, or unknown), and squamous histology (versus non-squamous). Of 264 patients with disease progression, 48.5% received subsequent drug therapy. Median OS-2 was longer with ICI alone (9.9 months) or ICI-chemotherapy (11.8 months) than platinum doublet chemotherapy (6.7 months.) For recurrences < 6 months from the last durvalumab infusion, OS-2 were similar across treatment groups. In the studied cohort, OS was significantly shorter for patients ≥ 75 years of age treated with cCRT followed by durvalumab compared to those < 65 years. Post-progression systemic therapy was associated with modest efficacy, underscoring the need for new therapies.

Serum CYFRA 21-1 as a Prognostic Marker in Non-Small-Cell Lung Cancer Patients Treated with Immune Checkpoint Inhibitors.

Background: A prognostic marker in patients with non-small-cell lung cancer (NSCLC) treated with anti-PD-1/PD-L1 antibodies must be established. This study explored serum cytokeratin fraction 21-1 (CYFRA 21-1), which represents a squamous cell histology, as a prognostic factor in anti-PD-1/PD-L1 antibody treatment, stratifying by histology and treatment regimen. Methods: This study retrospectively evaluated patients with advanced NSCLC without driver mutations receiving anti-PD-1/PD-L1 antibodies between November 2015 and March 2023. Cutoff values for CYFRA 21-1 and carcinoembryonic antigen (CEA) were 3.5 and 5.0 ng/mL, respectively. The Kaplan-Meier method and a log-rank test were conducted. The Cox proportional hazards model was utilized for univariate and multivariate analyses. Results: This study included 258 patients. The squamous NSCLC group demonstrated a shorter overall survival (OS) than the non-squamous NSCLC group (median, 17.8 vs. 23.7 months, p = 0.141). Patients with high serum CYFRA 21-1 and CEA levels exhibited a significantly shorter OS than those with normal levels (median, 11.7 vs. 32.7 months, p < 0.005; 15.8 vs. 29.7 months, p < 0.005). The multivariate analysis identified a performance status (PS) of ≥2, a PD-L1 expression of ≥50%, and a serum CYFRA 21-1 of >3.5 ng/mL as independent prognostic factors. Patients with high serum CYFRA 21-1 levels exhibited a significantly shorter OS even focusing on non-squamous NSCLC, anti-PD-1/PD-L1 antibody and chemotherapy combination therapy, or anti-CTLA-4 antibody combination therapy. Conclusion: Serum CYFRA 21-1 is a poor prognostic marker for patients with NSCLC receiving anti-PD-1/PD-L1 antibody treatment even when stratifying by histology or treatment regimen.

Longitudinal liquid biopsy predicts clinical benefit from immunotherapy in advanced non-small cell lung cancer

High heterogeneity in clinical benefit characterizes the use of immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC). We prospectively enrolled 113 advanced NSCLC patients treated with ICIs and performed liquid biopsy at the time of ICI start (T1), after 3 weeks (T2) and at the time of radiological evaluation (T3). Molecular variables were associated with outcome endpoints: cfDNA quantification, its dynamic change (∆T2–T1), variant allele frequency (VAF) of the gene with the highest frequency detected at baseline with NGS (maxVAF) and its dynamic change (∆T2–T1). At multivariate analysis, PD-L1 negativity, T1 cfDNA, cfDNA increase (∆T2–T1), and T2 VAF were significantly associated with shorter progression-free survival (PFS); PD-L1 negativity, squamous histology, T1 cfDNA, cfDNA (∆T2–T1) increase, and T2 maxVAF affected overall survival (OS). Among high PD-L1 expressing patients treated in first-line, elevated T2 maxVAF and cfDNA increase (∆T2–T1) correlated with worse PFS; higher T2 maxVAF and cfDNA increase (∆T2–T1) with worse OS. Derived integrated models were used to build nomograms and categorize different risk groups.

TROPION-Lung01 Results Indicate PFS Benefit With Datopotamab Deruxtecan Over Docetaxel in Previously Treated Nonsquamous NSCLC: A Critique and a Question

This commentary aims to point out how the results of the TROPION-LUNG01 study stress the "positive aspects" of the results, specifically, the increase in PFS, but hardly mention the potential harm to patients with squamous histology and lacks information on binary data (progression-free / progression, (alive/death) as per CONSORT guidelines. Here, we also remark on the need for adherence to CONSORT guidelines to inform on the absolute and relative risks of Randomized Controlled Trials (RCT). We emphasize the need for further research to develop a framework of how oncologists might explain the differences between PFS and OS in simple terms for a lay audience to improve a more informed decision of patients to embark on any cancer treatment.

A Review of Surgical Outcomes of Management of Sinonasal Malignancies: A 8-Year of Clinical Experience (2013-2021) at the Tertiary Centre, Sarawak.

Sinonasal carcinoma, a rare and challenging malignancy, originating in the nasal cavity and paranasal sinuses, poses diagnostic and management complexities. This 8-year retrospective analysis at Sarawak General Hospital aims to elucidate demographic trends, histopathological entities, and management outcomes, shedding light on this multifaceted malignancy. Emphasizing the significance of accurate histopathological classification, the study explores the impact on prognostication and treatment strategies. Spanning 2013 to 2021, the study involved 54 patients with sinonasal malignancies. Demographic, clinical, and histopathological details were examined, adhered to the AJCC staging criteria. Analysis involved demographic distributions, tumour characteristics, treatment modalities, and instances of treatment failure. Statistical analysis was done using SPSS version 29.02. The cohort, predominantly male (57.4%) and of Iban ethnicity (44.4%), with a mean age of 52.8 years, exhibited diverse histopathologies, with squamous cell carcinoma as the most common (38.9%). Epistaxis and nasal blockage were common clinical presentations. Advanced stages (III and IV) were prevalent, with the nasal cavity as the primary site. Surgical interventions, mainly endoscopic endonasal excision, were complemented by adjuvant therapies. Complications occurred in 24% of cases. The study highlights a male predilection, occupational risk factors, and a significant association between tobacco smoking and sinonasal cancers. Surgical interventions predominantly utilized the endoscopic approach. Despite a mean survival of 46.6 months, treatment failure occurred in 29.6% of cases, with recurrence and metastasis. Histopathological analysis revealed comparable 5-year disease survival rates between squamous and non-squamous histologies. Treatment failure was significantly associated with the mode of surgery, with open surgery showing a lower incidence. However, nodal status, histopathology types, T staging, and overall staging did display positive associations with treatment failure. This 8-year review provides comprehensive insights into sinonasal carcinoma, addressing demographic, clinical, and histopathological dimensions. The study underlines the complexity of managing this challenging malignancy, emphasizing the need for a holistic approach to patient care. The findings contribute to the understanding of sinonasal carcinoma, guiding clinical decision-making and fostering further research.

Palbociclib in Patients With Head and Neck Cancer and Other Tumors With CDKN2A Alterations: Results From the Targeted Agent and Profiling Utilization Registry Study.

Targeted Agent and Profiling Utilization Registry is a phase II basket trial evaluating the antitumor activity of commercially available targeted agents in patients with advanced cancer and targetable genomic alterations. Two cohorts of patients with cyclin-dependent kinase inhibitor 2A (CDKN2A)-mutated tumors treated with palbociclib are reported: one with head and neck cancer (HNC) with both squamous and nonsquamous cell histologies, and one with histology-pooled (HP) cancers. Eligible patients had measurable disease, Eastern Cooperative Oncology Group performance status 0-2, adequate organ function, and no standard treatment options. The primary end point was disease control (DC), defined as objective response (OR) or stable disease (SD) of at least 16+ weeks duration. For the HNC cohort, Simon's two-stage design with a null DC rate of 15% versus 35% (power = 0.85; α = .10) was used. For the HP cohort, the null hypothesis of a DC rate of 15% was rejected if the lower limit of a one-sided 90% CI was >15%. Secondary end points included OR, safety, progression-free survival, overall survival, duration of response, and duration of SD. Seventy patients with HNC (N = 28) or HP cancers (N = 42) were treated with palbociclib. For the HNC cohort, DC and OR rates were 40% (one-sided 90% CI, 27 to 100) and 4% (95% CI, <1 to 18), respectively. The null hypothesis was rejected (P = .002). For the HP cohort, DC and OR rates were 13% (one-sided 90% CI, 6 to 100) and 5% (95% CI, <1 to 17), respectively. The null hypothesis was not rejected. Thirty-one of 70 patients experienced treatment-related grade 3 to 4 adverse events (AEs) or serious AEs, the most common including neutropenia, thrombocytopenia, and leukopenia. Palbociclib met prespecified criteria to declare a signal of activity in patients with HNC with CDKN2A alterations, but not in the HP cohort.

Tumor involvement of the trigone and urethra at the time of robot-assisted radical cystectomy is associated with adverse oncological outcomes

IntroductionThe trigone/urethra (T/U) has a distinct embryologic origin and a different histologic morphology compared to the rest of the urinary bladder. We sought to determine the association between tumors involved in the T/U and the presence of variant histology, pathologic, and oncologic outcomes in patients who underwent robot-assisted radical cystectomy (RARC). MethodsTumor location was classified into 2 groups: tumors in the bladder walls only, or tumors in the T/U area, with or without involvement of other bladder walls. Univariable and multivariable Cox regression models were used to determine the association between T/U with recurrence-specific (RSS), cancer-specific (CSS), and overall survival (OS). Results608 patients who underwent RARC were identified, T/U involvement occurred in 191 (31%). Patients in the T/U group were more likely to have pT3/pT4 (57% vs. 42%, P < 0.01), positive surgical margins (21% vs. 9%, P < 0.01), and received salvage chemotherapy more frequently (16% vs. 8%, P < 0.01). Squamous variant histology was more frequent in the T/U group (25% vs. 17%, P = 0.02). On multivariable analysis, T/U location was independently associated with RSS (HR1.63, 95% CI 1.23–2.16, P < 0.01) and CSS (HR1.50, 95% CI 1.04–2.16, P = 0.02) but not OS. ConclusionResidual T/U tumor involvement was associated with a higher risk of an advanced tumor stage, positive margin, cancer recurrence, and cancer-specific death.

Nivolumab plus ipilimumab with chemotherapy for non–small cell lung cancer with untreated brain metastases: A multicenter single-arm phase 2 trial (NIke, LOGiK 2004)

BackgroundThe effect of dual immunotherapy combined with platinum-based chemotherapy on untreated brain metastases derived from non–small cell lung cancer (NSCLC) has remained unclear. MethodsThis multicenter single-arm phase 2 study enrolled patients with chemotherapy-naïve advanced NSCLC and at least one brain metastasis ≥ 5 mm in size that had not been previously treated. Patients received nivolumab plus ipilimumab combined with platinum-doublet chemotherapy (two cycles), followed by nivolumab-ipilimumab alone. The primary endpoint of the study was intracranial response rate as determined by modified Response Evaluation Criteria in Solid Tumors (RECIST) for brain metastases of ≥ 5 mm as target lesions. ResultsA total of 30 patients from 18 institutions was enrolled in this study. The median age was 66.5 years (range, 47–83 years), and 26 patients (87 %) had a non–squamous cell carcinoma histology. The median size of all target brain lesions was 8.4 mm, with a range of 5–39 mm. The intracranial response rate assessed by modified RECIST was 50.0 % (95 % CI, 33.2–66.8 %), with the rate of complete response being 20.0 %, and the study met its primary endpoint. The systemic response rate was 53.3 % (95 % CI, 36.1–69.8 %), and responses for intracranial and extracranial lesions were generally consistent. The median intracranial progression-free survival was 8.1 months, and both the median intracranial duration of response and time to brain radiotherapy were not reached. ConclusionNivolumab plus ipilimumab combined with platinum-based chemotherapy showed promising intracranial activity in NSCLC patients with untreated brain metastases. Trial registrationjRCT071210019.

Datopotamab Deruxtecan Versus Docetaxel for Previously Treated Advanced or Metastatic Non-Small Cell Lung Cancer: The Randomized, Open-Label Phase III TROPION-Lung01 Study.

The randomized, open-label, global phase III TROPION-Lung01 study compared the efficacy and safety of datopotamab deruxtecan (Dato-DXd) versus docetaxel in patients with pretreated advanced/metastatic non-small cell lung cancer (NSCLC). Patients received Dato-DXd 6 mg/kg or docetaxel 75 mg/m2 once every 3 weeks. Dual primary end points were progression-free survival (PFS) and overall survival (OS). Objective response rate, duration of response, and safety were secondary end points. In total, 299 and 305 patients were randomly assigned to receive Dato-DXd or docetaxel, respectively. The median PFS was 4.4 months (95% CI, 4.2 to 5.6) with Dato-DXd and 3.7 months (95% CI, 2.9 to 4.2) with docetaxel (hazard ratio [HR], 0.75 [95% CI, 0.62 to 0.91]; P = .004). The median OS was 12.9 months (95% CI, 11.0 to 13.9) and 11.8 months (95% CI, 10.1 to 12.8), respectively (HR, 0.94 [95% CI, 0.78 to 1.14]; P = .530). In the prespecified nonsquamous histology subgroup, the median PFS was 5.5 versus 3.6 months (HR, 0.63 [95% CI, 0.51 to 0.79]) and the median OS was 14.6 versus 12.3 months (HR, 0.84 [95% CI, 0.68 to 1.05]). In the squamous histology subgroup, the median PFS was 2.8 versus 3.9 months (HR, 1.41 [95% CI, 0.95 to 2.08]) and the median OS was 7.6 versus 9.4 months (HR, 1.32 [95% CI, 0.91 to 1.92]). Grade ≥3 treatment-related adverse events occurred in 25.6% and 42.1% of patients, and any-grade adjudicated drug-related interstitial lung disease/pneumonitis occurred in 8.8% and 4.1% of patients, in the Dato-DXd and docetaxel groups, respectively. Dato-DXd significantly improved PFS versus docetaxel in patients with advanced/metastatic NSCLC, driven by patients with nonsquamous histology. OS showed a numerical benefit but did not reach statistical significance. No unexpected safety signals were observed.

375. ROLE OF RECURRENTIAL LYMPHADENECTOMY BY MINIMALLY INVASIVE APPROACH IN THE SURGICAL TREATMENT OF ESOPHAGEAL CANCER

Abstract Background Esophageal cancer is an aggressive tumor, which is normally diagnosed in more advanced stages. The anatomical characteristics of the esophagus allow rapid spread to neighboring structures, and the extensive lymphatic drainage network facilitates tumor spread even in early stages. Lymphatic spread is the single most important prognostic factor and is a good predictor of disease-free survival. The objective of this study is to present the esophageal neoplasms operated in our center in which we have performed a recurrent lymphadenectomy, describing the postoperative complications, the presence of lymph node metastases and their influence on the evolutionary course of the disease. Methods Retrospective, observational, descriptive and analytical study in which all patients operated on for esophageal neoplasia from January 2019 to January 2024 are included. All patients have been operated on by the same surgical team specialized in esophagogastric surgery. Quantitative variables are described as mean and standard deviation, and qualitative variables are described as absolute number and percentage. The univariate methods used are Pearson's X2 or Student's t for independent samples. A logistic regression has also been performed to study factors that influence in survival. The IBM SPSS Statistics 22 program was used to analyze the data. Results 89 patients have been operated on, 70 three-stage esophagectomies and 16 two-stage. In 60,6% cases it was adenocarcinoma and 33,7% squamous cell histology. Recurrent lymphadenectomy was performed in all of them, 31 expanded and 58 total. 6 patients with recurrent lymph nodes affected, 2 on the right side, 3 on the left and 1 bilateral. 15% patients with tumors &amp;gt;T2 presented recurrent affected lymph nodes, increasing to 20% in adenocarcinomas. 20 recurrent nerve injuries, all of them transient except 3. Statistically significant relationship has been found between the number of affected lymph nodes and disease-free survival time (p = 0.045). Conclusion Mediastinal and recurrent lymphadenectomy in esophageal cancer influences in the number of positive nodes obtained after surgery. This could determine a more advanced staging of the disease, which allows adaptation of the adjuvant treatment, influencing in the time free of disease. Most injuries caused by this type of lymphadenectomy can be managed with conservative treatment.

Outcome of Patients with Early Glottic Laryngeal Carcinoma Treated with Radical Radiotherapy

Introduction: Glottic cancer is the most common laryngeal cancer and it has the most favorable prognosis, mainly if diagnosed early. Ideally, early glottic cancer (T1–T2 N0) should be managed with a single modality either microsurgery or definitive Radiotherapy. The local control rate with definitive radiotherapy is approximately 83–95% for T1 and 70–80% for T2 lesions. This study intends to find out the treatment outcome in early glottic cancer treated with radical radiation treatment from 1st January 2014 to 31st December 2019 at our center. Methods: This was a retrospective analysis of medical records and radiation charts of all patients of early stage glottis cancer who underwent radiation treatment from 1st January 2014 to 31st December 2019 at our centre. The statistical analysis was done using SPSS version 20.0.Continuous variables such as age was summarized in terms of either mean ± Standard Deviation or median (inter quartile range) depending on the statistical distribution of data. Categorical variables were e pressed in terms of frequency and percentage. Survival analysis was done using Kaplan Meier curves. Results: A total of 91 patients underwent radical radiation for early glottic carcinoma at our centre. The median age was 63 years (42-85 years). Out of them 94% were males and 6% were females. 78% of patients had stage 1 disease and 22% had stage 11 disease. 52% of patients had co morbidities and 48% did not have any comorbidity All cases had Squamous cell carcinoma histology. 59% of patients had anterior commissure involvement. 12 out of 91 (13%) patients developed local recurrence on follow up. The five year disease free survival was 84.3%. The five year overall survival was 87.7%. There was a statistically significant difference in survival between stage I and stage II. Conclusion: For T1–T2 glottic carcinomas, definitive RT can provide a good term local control and survival with the preservation of the normal structure and function of larynx.

Outcomes of Squamous Cell Carcinoma Oropharynx in Elderly Patients Treated with External Beam Radiation Therapy - A Retrospective Study from Tertiary Care Cancer Center - India

Background: Majority of Elderly patients with oro-pharyngeal Squamous cell (OPSCC) are treated with External beam Radiation Therapy(EBRT) alone, the benefit of chemotherapy after 70years is doubtful, we aim to analyze outcomes and morbidity in elderly OPSCC treated with EBRT. Methods: Retrospective study, all patients with Oropharyngeal squamous cell carcinoma histology, more than or equal 70 years of age, having performance status Eastern Cooperative Oncology Group (ECOG) 0-2, All stages other than metastatic disease, who were registered and treated with Radical radiation therapy alone at our institute from January 2015 to December 2018 were included. Having ECOG performance status 3-4, Patients treated with brachytherapy, or concurrent chemoradiation, synchronous primaries, re-irradiation are excluded from this study. Entire cohort of 30 patients (25 male, 5 female) were treated with EBRT, who received total dose 50Gy to 66Gy were included for analysis. Results: 90% of cases (27/30) were locally advanced (Stage III &amp; IV), At median follow up duration of 18months (range 1 to 81 months), at 3, 4, and 5 years OS was 36.7% (95% Confidence interval (CI) = 19.4% - 54%), 23.3% (95% CI = 8.2% - 38.4%) and 19.4% (95% CI = 5.1 - 33.7%) respectively. Conclusion: compared to young, elderly OPSCC has poor outcomes, this subset may do as well as young people if treated with multi modality treatment with proper selection. By addressing the risk factors , using preventive measures, early detection , and ensuring access to the adequate health care facilities are pivotal in reducing the burden of cancer. Poor representations of this subset of population in clinical trails, facing challenges treating with multi modality approach may be one of the reason for poor outcomes compared to the young patients, needs prospective trails specifically focusing on this group of patients should be performed.

Multidisciplinary team meetings improve survival in patients with esophageal cancer.

Multidisciplinary team meetings (MDTs) are recommended for patients with esophageal cancer. Improved staging, timeliness to surgery and better adherence to guidelines have been attributed to MDTs, but there are few studies published on the MDTs' effect on survival. All patients with esophageal cancer in Sweden between 2006 and 2018 were grouped according to whether they had been discussed at an MDT as part of their clinical pathway. Factors affecting group allocation were explored with multivariable logistic regression, and the impact of MDT on survival was studied with Cox-regression and the Kaplan-Meier estimator. Of 6837 included patients, 1338 patients (20%) were not discussed at an MDT. Advanced age (80-90years; odds ratio [OR] 0.25, 0.16-0.42 (95% confidence interval)) and clinical stage IVb (OR 0.65, 0.43-0.98) decreased the probability of being presented at an MDT, whereas high education level (OR 1.31, 1.02-1.67), being married (OR 1.20, 1.01-1.43), squamous histology (OR 1.50, 1.22-1.84) and later year of diagnosis (OR 1.33, 1.29-1.37 per year) increased the probability of an MDT. In multivariable adjusted analysis, MDT discussion was associated with improved survival (hazard ratios 0.72, 0.66-0.78) and median survival increased from 4.5 to 10.7months. MDTs were associated with improved survival for esophageal cancer patients. Elderly patients with advanced disease and poor socioeconomic status were less likely to be presented at an MDT, but had clear survival-benefits if they were discussed in a multidisciplinary setting.

Induction chemotherapy backbone in frail patients with advanced NSCLC treated with chemotherapy plus pembrolizumab: a single institution retrospective audit of dose intensities from modified regimens.

Guidelines historically recommended mono-chemotherapy for the 1st line treatment of elderly patients with non-small cell lung cancer (NSCLC) and poor performance status (PS). Nowadays, there is no clear indication whether chemo-immunotherapy (chemo-IO) combinations can be effectively delivered in this population. We collected induction chemotherapy data in consecutive patients with advanced NSCLC treated with carboplatin-based chemotherapy regimens plus pembrolizumab, to compute the received dose intensity (RDI) from standard regimens or patient-tailored regimens modified due to age, comorbidities and PS. Comorbidities were stratified according to the comorbidity-polypharmacy score (CPS). The established cut-off of ≥85% for RDI was used to define adequate delivery. 116 pts were treated from Feb-20 to July-23, of whom 96 and 20 with non-squamous and squamous NSCLC, treated with carboplatin-pemetrexed or carboplatin-paclitaxel doublets plus pembrolizumab, respectively. The majority of patients were aged ≥ 70 years (52.6%), the median CPS was 5, with 58.6% having a CPS ≥5, whilst 47.4%, 44.8% and 7.8% had an Eastern Cooperative Oncology Group (ECOG) - PS of 0, 1 and 2, respectively. PD-L1 TPS were <1% in 31.9% and 1-49% in 65.4%. Overall, 47.4% received a priori modified regimens due to poor PS, age, or comorbidities. Among patients with non-squamous NSCLC, median received doses of carboplatin and pemetrexed were 1.37 AUC/week and 138.8 mg/m2/week, with RDIs of 86% and 75% (p < 0.01) for patients treated with standard or modified regimens, respectively. Of note, the RDI was 57.9% among patients with ECOG-PS 2. However, patients treated with modified regimens experienced similar toxicities as those treated with standard regimens, despite being older (p < 0.01), with higher PS (p < 0.01) and more comorbid (p = 0.03). Patients treated with modified regimens achieved a shorter survival (7.1 vs 13.9 months), which is comparable to IO-free historical controls. Among patients with squamous NSCLC, 90% received modified regimens upfront, with median received doses of carboplatin and paclitaxel of 1.19 AUC/week and 40 mg/m2/week, and an overall RDI of 73.5%. Although regimen modifications ensure a safe administration of chemotherapy plus pembrolizumab in frail patients, the RDI seems to be subtherapeutic, especially in those with squamous histology. Dedicated trials are needed to implement combination strategies in this population.

Clinical significance of chronic pulmonary aspergillosis in lung cancer patients undergoing anticancer drug therapy.

Advances in anticancer drugs for lung cancer (LC) have improved the prognosis of LC. Chronic pulmonary aspergillosis (CPA) is a progressive and often exacerbating respiratory disease with a poor prognosis. To date, the prognosis of LC complicated by CPA has not been elucidated. This study investigated the clinical implications of concomitant CPA in patients with LC undergoing anticancer drug treatment. Between January 2010 and May 2020, we consecutively enrolled patients with LC complicated with CPA at five different institutions in Japan. We analyzed patients with LC complicated by CPA who received anticancer drug treatment. A total of 10 patients with LC complicated by CPA received anticancer drug treatment. The median overall survival (OS) was 14.57 months (95% confidence interval [CI]: 5.37-21.67). The cause of death in all patients was LC. Six of the seven patients with LC did not show worsening pulmonary aspergillosis lesions during the anticancer drug treatment. Although two patients discontinued anticancer drug treatment due to pneumonitis, CPA complications did not interfere with the continuation of anticancer drug treatment. In univariate analyses, squamous histology (p = 0.01) and body mass index (<18.5 kg/m2) (p = 0.0008) were significantly associated with poorer OS. This study demonstrated that the cause of death in LC patients with concomitant CPA who received anticancer drug treatments and effective antifungal treatment was LC progression. Further large-scale studies are needed to identify the effect of CPA in patients with LC.

Real-World Biomarker Test Ordering Practices in Non-Small Cell Lung Cancer: Interphysician Variation and Association With Clinical Outcomes.

Patients with metastatic or advanced non-small cell lung cancer (NSCLC) need biomarker testing, including, in most cases, anaplastic lymphoma kinase (ALK), epidermal growth factor receptor (EGFR), and PD-L1, to identify options for targeted therapies and to optimally incorporate immune checkpoint inhibitors into therapeutic regimens. We sought to examine real-world patterns of biomarker testing, quantify interphysician practice variation, and correlate testing with clinical outcomes. We extracted real-world data from a nationwide electronic health record-derived deidentified database from 17,165 patients diagnosed with advanced NSCLC between 2018 and 2021 and receiving care in the community setting. We analyzed data using descriptive analyses, fixed- and mixed-effects logistic regression models, and proportional hazard models. Only 67% of all 17,165 patients and 77% of patients with nonsquamous, metastatic NSCLC had ALK, EGFR, and PD-L1 testing within 90 days of diagnosis. Later diagnosis year (2019-2021 compared with 2018) was associated with higher rates of ALK, EGFR, and PD-L1 testing; stage IIIB/C disease (compared with stage IV), squamous histology, and Black or African American race were associated with lower rates. Interphysician variation was substantial with a median odds ratio between physicians (adjusted for patient factors) of 1.78 for ALK, EGFR, and PD-L1 testing. Patients with nonsquamous, metastatic NSCLC had significantly prolonged survival if tested with all three biomarkers (median, 364 days for all three v 180 for none of the three; hazard ratio, 0.67; P < .001). Rates of biomarker testing appear suboptimal with substantial interphysician variation. Testing correlates with improved survival, although causality cannot be proven from this study. Additional work is needed to address the underlying causes of suboptimal test ordering.

Adjuvant Hysterectomy in Patients After Radiation for Locally Advanced Cervical Cancer: A Single-Center Prospective Longitudinal Study.

Residual or recurrent cervical cancer post-CCRT is a challenging clinical issue, even though there has been much effort in recent decades to increase patient survival after radiation. There is a paucity of literature regarding the role of hysterectomy in recurrent/residual disease after radiation in LACC patients. Such a procedure is controversial and not routinely performed because of difficulties in obtaining tumor-free margins and the high rate of associated morbidity. Evaluate outcomes and morbidities in patients who had undergone hysterectomy for residual or recurrent disease after radiation in LACC patients. This is a prospective observational study on radiotherapy-treated LACC patients (IIB-III) with residual disease or recurrent disease who have undergone adjuvant hysterectomy. This study has been conducted at AHPGIC, Cuttack, with a sample size of 30 patients. 18/30 patients underwent extrafascial hysterectomy, and rest 12 patients had radical hysterectomy. No significant difference in complications, achieving tumor free margins or recurrences post adjuvant hysterectomy based on the radicality of surgery was observed. 5 cases of recurrences post-adjuvant hysterectomy were detected. Some of the factors which had significant association with recurrences post adjuvant hysterectomy were non squamous histology, no preoperative brachytherapy, deep stromal invasion and positive surgical margins. Median follow-up time was 14months (12-27months). This study shows that adjuvant hysterectomy is feasible with good outcome and acceptable morbidity after chemoradiotherapy in cervical cancer patients "If selection of patients for adjuvant hysterectomy is appropriate."