Squamous Cell Carcinoma Histology Research Articles

Real-world treatment patterns, biomarker testing, and clinical outcomes of metastatic non-small cell lung cancer patients in the immunotherapy era.

Treatment for first-line (1L) metastatic non-small cell cancer (mNSCLC) changed with the introduction of immunotherapy. We describe treatment utilization and clinical outcomes in a real-world mNSCLC cohort in a 2.7-million-member state-mandated health provider. Newly diagnosed mNSCLC patients initiating systemic anti-cancer treatment (January 2017-December 2020) were identified from the National Cancer Registry. Real-world time on treatment (rwToT) was defined as the length of time between the first and last administration date of treatment. Real-world overall survival (rwOS) was estimated using Kaplan-Meier analysis. Outcomes were assessed at a minimum of 6 months' follow-up (cutoff: 30 June 2021). Among 843 patients, 85% had adenocarcinoma (NSQ) and 15% had squamous cell carcinoma (SQ) histology: of these, 43% and 26% were women, median age was 67 and 69 years, and 55% and 48% had 0-1 ECOG performance status, respectively (missing: 27% and 30%, respectively). Median follow-up for the entire cohort was 27.1 months (95% CI: 24.7-29.6). NSQ patients with no known EGFR/ALK/ROS1 aberrations received PD-1 inhibitor monotherapy (PDM) (N = 147) or combination (PDC) (N = 194) or platinum-based chemotherapy (PBC, N = 133). Median rwToT was 4.5 (95% CI: 3.5-7.6), 5.2 (95% CI: 4.6-7.6), and 2.3 (95% CI: 2.1-3.0) months, respectively; for the subgroup of patients with ECOG PS 0-1, rwToT was 9.4 (95% CI: 5.0-20.8), 7.1 (95% CI: 5.0-10.1), and 2.9 (95% CI: 2.2-4.1) months, respectively. Median rwOS from 1L was 12.5 (95% CI: 9.9-17.9), 14.8 (95% CI: 10.5-19.4), and 9.1 (95% CI: 7.1-11.5) months; for the subgroup of patients with ECOG PS 0-1, median rwOS was 25.1 [95% CI: 14.9-not reached (NR)], 17.6 (95% CI: 14.3-NR), and 11.3 (95% CI: 9.2-21.3) months, respectively. For ECOG PS 0-1 and PD-L1 ≥50% patients, median rwOS was 25.1 months (95% CI: 13.9-NR) and NR for PDM and PDC, respectively. For ECOG PS 0-1 and PD-L1 <50% patients, median rwOS was 14.3 (95% CI: 10.1-NR) and 11.2 (95% CI: 9.1-21.3) months for PDC and PBC, respectively. Our real-world data support the benefit of single-agent PD-1 inhibitor monotherapy for patients with PD-L1 high expression or PD-1 inhibitor combination for all patients diagnosed with mNSCLC with no known EGFR/ALK/ROS1 aberrations, initiating 1L treatment.

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.

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.

Clinical features, surgical management and outcome of squamous and basal cell carcinoma in squamates and chelonians.

Squamous cell carcinoma (SCC) is one of the most commonly diagnosed neoplastic disorders in reptiles. Recently, however, it has been demonstrated that basal cell carcinomas (BCCs) are frequently misclassified as SCCs. Several histological SCC and BCC variants have been characterised and their classification may allow the establishment of appropriate prognosis estimation and treatment approaches. To describe the clinical features and surgical outcomes of SCCs and BCCs diagnosed between 2010 and 2022 in reptiles. Thirty-three captive reptiles (21 squamates and 12 chelonians). Detailed clinical history, including staging and surgical outcomes, were performed. Statistical analysis assessed significant factors using Prism (v8.2.1). While SCC was predominantly diagnosed in lizards, BCC was most commonly diagnosed in chelonians, and both neoplasms mainly occurred in adult to aged, male individuals. Although the gross pathological findings were highly comparable between SCC and BCC, considerable variation could be seen according to the primary location (oral, cutaneous or epidermis of the shell). Humane euthanasia or noncurative intent surgeries were performed in a minority of the cases. Curative intent surgeries were successful in 19 of 27 cases during a 1- to 7-year follow-up period, yet recurrence was seen in 8 cases. The results of this study allowed the identification of significant high-risk prognostic factors for SCC and BCC in reptiles. This study contributes to predicting the clinical behaviour and prognosis of distinct SCC and BCC histological variants, and selecting the most appropriate treatment protocol.

Spatially fractionated radiotherapy (Lattice SFRT) in the palliative treatment of locally advanced bulky unresectable head and neck cancer

ObjectivesLocally advanced bulky unresectable head neck cancer causes significant tumor mass effects, leading to severe symptoms. This study aims to report the safety and outcomes in patients undergoing Lattice spatially fractionated radiotherapy (Lattice SFRT) for locally advanced bulky unresectable head and neck cancer. MethodsPatients with bulky head and neck cancer received Lattice SFRT between June 2022 and June 2023. Lattice SFRT was administered in 2–3 fractions of 12 Gy (Gy) using 6-megavolt (MV) photon beams through a multileaf collimator (MLC) based on VMAT technology. The primary endpoints were symptomatic and tumor response rates. Secondary endpoints were overall survival, local control, and acute and late toxicity rates. Results19 consecutive patients meeting the study criteria were identified, predominantly with squamous cell carcinoma histology. The median patient age was 62 years (range 39–79 years), and the median tumor volume was 208 cc (cc) (range 48–701 cc). All patients completed radiotherapy. Among all investigated patients, 16 of 19 (84.2 %) patients achieved an objective response, including 10 individuals achieved a partial response (PR), with 3 of them exhibiting regression exceeding 75 %. 17 patients showed symptom improvement to varying degrees. Acute toxicity of Radiation Therapy Oncology Group (RTOG) grade 1 or higher occurred in 5 patients, while no grade 3 adverse events was observed. ConclusionsLattice SFRT proves to be a viable treatment option for the palliative management of bulky head and neck cancer. In the palliative setting, Lattice SFRT offers timely symptom relief, enhancing patient quality of life. Treatment toxicity remains within an acceptable range. Continued optimization of Lattice SFRT delivery and patient selection can benefit from further data on the feasibility and efficacy of this radiation modality.

Questionnaire survey on cervical cancer screening and HPV awareness among patients at a local cancer center in Japan

BackgroundThe incidence of cervical intraepithelial neoplasia is increasing in Japan. Although human papillomavirus (HPV) vaccination and cancer screening are crucial in preventing cancer-related mortality, the cervical cancer screening rate in Japan was only approximately 43.6% in 2022. This study aimed to conduct an epidemiological analysis of cervical cancer by collecting data from individual patients.MethodsA questionnaire survey was administered to patients who visited our hospital between January 2017 and July 2023 owing to abnormal cervical cytological findings or a cancer diagnosis. Patients answered questions regarding their history of cervical cancer screening as well as their knowledge of HPV and cervical cancer.ResultsDuring the study period, 471 patients participated in the survey, with 35 declining to participate. Patients with Stage 1b1–4b primarily sought medical attention due to self-reported symptoms (P < 0.001); however, they were less likely to have undergone cervical cancer screening (P < 0.001). Additionally, older patients were less likely to be aware of the association of HPV with cervical and other cancers. Notably, 28 of the 129 patients with stage 1b1–4b cancer underwent cervical cancer screening within 2 years. The tumor location within the endocervical canal emerged as a significant factor contributing to the difficulty for an accurate diagnosis of precancerous or cervical cancer during cervical screening. Furthermore, non- squamous cell carcinoma (SCC) histology was another possible factor.ConclusionsOur findings suggest the need to widely disseminate information regarding the significance of cancer screening to increase cancer screening rates. Moreover, establishing strategies for improving the accuracy of detecting lesions during screening for non-SCC and endocervical canal tumors is crucial.

Immunohistochemistry of p53 surrogates TP53 mutation as an accurate predictor for early-relapse of surgically resected stage I-III lung adenocarcinoma

IntroductionTP53 is a strong tumor suppressor gene; its deactivation contributes to carcinogenesis and influences clinical outcomes. However, the prognostic influence of p53 deactivation on early relapse in patients with surgically resected non–small cell lung cancer remains unclear. Materials and methodsA cohort of 170 patients with primary stage I through III lung adenocarcinoma (LADC) and lung squamous cell carcinoma who underwent complete resection at Tokyo Medical and Dental University was screened for TP53 mutations using panel testing, and association studies between TP53 mutations and clinical data, including histology and postoperative recurrence, were performed. The association between TP53 mutations and postoperative recurrence was validated using data from 604 patients with MSK-IMPACT from The Cancer Genome Atlas. Additional immunohistochemistry for p53 was performed on some subsets of the Tokyo Medical and Dental University population. ResultsMutations in TP53 were recurrently observed (35.9%; 61 out of 170) in the Tokyo Medical and Dental University cohort. In the histology-stratified analysis, patients with LADC histology showed TP53 mutations that were associated with poor relapse-free survival (log-rank test; P = .020), whereas patients with lung squamous cell carcinoma histology showed TP53 mutations that were not (P = .99). The poor prognosis of TP53 mutation-positive LADCs was validated in The Cancer Genome Atlas-LADC cohort (log-rank test; P = .0065). Additional immunohistochemistry for p53 in patients with LADC histology in the Tokyo Medical and Dental University cohort showed a significant correlation between TP53 mutations and abnormal IHC pattern of p53 (Cramer's correlation coefficient V = 0.67). ConclusionsTP53 mutation is a potential marker for worse prognosis in surgically resected LADC; immunohistochemistry for p53 could be a surrogate method to identify patients with LADC with a worse prognosis.

Mapping incidence and survival of non-small-cell lung cancers stratified by mutation type in southern Appalachia: A single center retrospective study.

e20568 Background: Non-small cell lung cancer (NSCLC) is often a mutation-driven disease with variability in incidence and survival depending on location as seen in population-based cohort studies. Our study aims to delineate these differences based on molecular testing for these mutations in our study cohort at East Tennessee State University - Quillen College of Medicine, which is based on patients from east Tennessee, western North Carolina, and southwestern Virginia. Methods: We obtained pathology results of 294 patient samples with advanced/metastatic NSCLC from our cancer center/health system database over a 5 year period. PDL-1 was tested in all patients. Fluorescent in-situ hybridization (FISH) testing for common pathogenic driver mutations such as EGFR, ALK, ROS1, RET, MET and PTEN were performed as is standard of care. Molecular sequencing was performed and included over 40 genetic mutations and 2 biomarkers, several of which today are considered targetable for advanced NSCLC, per standard of care. Incidence of different mutations was measured in our patient population. Overall survival was calculated with date of diagnosis available based on pathology report and date of patient expiration obtained from electronic medical records. Data analysis was performed to ascertain which mutations carried an increased risk of death. Results: The TP53 mutation was very common, seen in 85% of squamous cell carcinoma (SCC) histology and 55% of adenocarcinoma. Similarly, incidence of PTEN deletion by FISH was noted to be 52% in SCC and 31% in adenocarcinoma. EGFR mutations were rare, seen in only 3% of tested patients. We had an incidence of KRAS G12C mutations at 11% overall, but it was present in up to 18% of adenocarcinomas. BRAF was seen in 4.8% of all cases, 8% of adenocarcinomas and 2% of SCC. Since there were more than 2 predictors, Cox proportional-hazards regression model was fit. Due to either having all negative values or very few positive values, the variables CCND1, CDKN2B, ERBB2, ERBB4, FGFR, FGFR2, MET, MSI, NRAS, PDGFRA, RET, RS01, SCR were excluded from analysis. A total of 156 samples were used in final analysis. After model building, it was found that BRAF and KRAS G12C mutation were significant predictors of survival by hazard ratios for death. Conclusions: In our unique patient population, there was a greater incidence of deleterious TP53 mutations and PTEN deletions compared to the general North American advanced/metastatic NSCLC population. Although BRAF and KRAS G12C mutations were not at a greater incidence in comparison to the rest of North America, they were notably significant predictors of survival, conferring nearly 3.4 and 2.7 times increased risk of death in our study. [Table: see text]

Prognostic implications of STK11 with different mutation status and its relationship with tumor-infiltrating immune cells in non-small cell lung cancer.

Mutations in STK11 (STK11Mut) gene may present a negative impact on survival in Non-small Cell Lung Cancer (NSCLC) patients, however, its relationship with immune related genes remains unclear. This study is to unveil whether overexpressed- and mutated-STK11 impact survival in NSCLC and to explore whether immune related genes (IRGs) are involved in STK11 mutations. 188 NSCLC patients with intact formalin-fixed paraffin-embedded (FFPE) tissue available for detecting STK11 protein expression were included in the analysis. After immunohistochemical detection of STK11 protein, patients were divided into high STK11 expression group (STK11High) and low STK11 expression group (STK11Low), and then Kaplan-Meier survival analysis and COX proportional hazards model were used to compare the overall survival (OS) and progression-free survival (PFS) of the two groups of patients. In addition, the mutation data from the TCGA database was used to categorize the NSCLC population, namely STK11 Mutated (STK11Mut) and wild-type (STK11Wt) subgroups. The difference in OS between STK11Mut and STK11Wt was compared. Finally, bioinformatics analysis was used to compare the differences in IRGs expression between STK11Mut and STK11Wt populations. The median follow-up time was 51.0 months (range 3.0 - 120.0 months) for real-life cohort. At the end of follow-up, 64.36% (121/188) of patients experienced recurrence or metastasis. 64.89% (122/188) of patients ended up in cancer-related death. High expression of STK11 was a significant protective factor for NSCLC patients, both in terms of PFS [HR=0.42, 95% CI= (0.29-0.61), P<0.001] and OS [HR=0.36, 95% CI= (0.25, 0.53), P<0.001], which was consistent with the finding in TCGA cohorts [HR=0.76, 95%CI= (0.65, 0.88), P<0.001 HR=0.76, 95%CI= (0.65, 0.88), P<0.001]. In TCGA cohort, STK11 mutation was a significant risk factor for NSCLC in both lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD) histology in terms of OS [HR=6.81, 95%CI= (2.16, 21.53), P<0.001; HR=1.50, 95%CI= (1.00, 2.26), P=0.051, respectively]. Furthermore, 7 IRGs, namely CALCA, BMP6, S100P, THPO, CGA, PCSK1 and MUC5AC, were found significantly overexpressed in STK11-mutated NSCLC in both LUSC and LUAD histology. Low STK11 expression at protein level and presence of STK11 mutation were associated with poor prognosis in NSCLC, and mutated STK11 might probably alter the expression IRGs profiling.

Abstract CT054: Amivantamab in wild-type advanced non-small cell lung cancer after disease progression on checkpoint inhibition and chemotherapy: Results from the phase 1b CHRYSALIS study

Abstract Background: Overexpression of EGFR and MET has been observed in wild-type (WT) adenocarcinoma and squamous non-small cell lung cancer (NSCLC; Huang L. J Thorac Oncol. 2014). Amivantamab (ami), an EGFR-MET bispecific antibody with immune cell-directing activity, demonstrated pre-clinical activity against WT tumors overexpressing EGFR and MET. We examined ami monotherapy activity in WT-NSCLC after disease progression on platinum-based chemotherapy and anti-PD-1 or PD-L1 therapy. Methods: The WT-Ad and WT-Sq cohorts of the CHRYSALIS study enrolled pateints (pts) with adenocarcinoma or squamous cell carcinoma histology, respectively, without evidence of EGFR, ALK, and MET Exon 14 skipping activating mutations. Pts received ami monotherapy at the approved dose (1050 mg; 1400 mg if ≥80 kg) weekly for the first 4 weeks and biweekly thereafter. Response was assessed by the investigator per RECIST v1.1. Plasma samples were collected pre-treatment, with ctDNA analyzed by Guardant Health (Redwood City, CA). Results: In the WT-Ad cohort, 41 pts received ami (30 with ≥1 post-baseline disease assessment; 11 discontinued due to adverse events [AEs], disease progression, or physician decision), with a median follow-up of 6.2 mo. The median age was 62 years, 63% were men, and 37% were Asian. The objective response rate (ORR) was 7% (3/41), the clinical benefit rate (CBR) was 29%, and the median duration of response (DoR) was 4.2 mo (95% CI, 4.1-not estimable [NE]). Among pts with detectable ctDNA (n=24), 9 pts had KRAS/HER2 mutations. The ORR for pts with and without KRAS/HER2 mutations was 0% (0/9) and 20% (3/15), respectively. The corresponding median PFS for pts with and without KRAS/HER2 mutations was 1.4 mo (95% CI, 1.4-NE) and 4.2 mo (95% CI, 1.6-NE), respectively. In the WT-Sq cohort, 14 pts received ami (12 with ≥1 post-baseline disease assessment; 2 discontinued), with a median follow-up of 6.3 mo. Median age in the WT-Sq cohort was 71 years, 57% were men, and 43% were Asian. ORR was 21% (3/14) with a median DoR that was NE and 2 pts with a DoR ≥6 mo. The overall CBR was 43% (6/14), median PFS was 4.0 mo (95% CI, 2.2-7.3), and median OS was NE. Most common treatment-emergent AEs in both cohorts were rash (grouped term; 66% for WT-Ad, 57% for WT-Sq) and infusion-related reactions (63% WT-Ad and 57% WT-Sq). Grade ≥3 treatment-related AEs (TRAEs) were reported in 17% of pts in the WT-Ad cohort and 21% the WT-Sq cohort. One (2%) pt in the WT-Ad cohort experienced grade 2 interstitial lung disease. Four pts in WT-Ad and 2 pts in WT-Sq cohort discontinued due to TRAEs. Conclusions: Ami demonstrated preliminary antitumor activity in pts with refractory WT squamous and adenocarcinoma NSCLC, particularly in those lacking KRAS/HER2 activating mutations. Safety profile was consistent with the previously reported monotherapy experience, and no new signals were identified. Citation Format: Byoung Chul Cho, Jonathan Goldman, Natasha Leighl, Filippo De Braud, Ki Hyeong Lee, François Ghiringhelli, Pilar Garrido, Julio Peguero, Benjamin Besse, Philippe Cassier, Nicolas Girard, Maria de Miguel, Rosa Alvarez, Alastair Greystroke, Yuichiro Ohe, Te-Chun Hsia, Joshua C. Curtin, Sanjib Chowdhury, Xuesong Lyu, Grace Gao, Siyang Qu, Patricia Lorenzini, Aastha Kapoor, Priya Kim, Mahadi Baig, Meena Thayu, Roland E. Knoblauch, Sandrine Hiret, Pascale Tomasini. Amivantamab in wild-type advanced non-small cell lung cancer after disease progression on checkpoint inhibition and chemotherapy: Results from the phase 1b CHRYSALIS study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT054.

Favourable surgical outcomes for either second primary lung cancer or intrapulmonary metastasis after resection of non-small-cell lung cancer.

Metachronous lung cancer arising after resection of non-small-cell lung cancer is either a second primary lung cancer (SPLC) or intrapulmonary metastasis (IPM) of the initial lung cancer; however, differential diagnosis is difficult. We evaluated the surgical outcomes of metachronous lung cancer in a combined population of patients with SPLC and IPM. A retrospective study of 3534 consecutive patients with resected non-small-cell lung cancer between 1992 and 2016 was conducted at 4 institutions. A total of 105 patients (66 males; median age, 70 years) who underwent a second pulmonary resection for metachronous lung cancer were included. Most patients (81%) underwent sublobar resection, and there was no 30-day mortality. All metachronous lung cancers were cN0, 5 were pN1-2. The postoperative comprehensive histologic assessment revealed SPLC (n = 77) and IPM (n = 28). The 5-year overall survival rate after the second resection was 70.6% (median follow-up: 69.7 months). A multivariable analysis showed that age >70 years at the second resection (P = 0.013), male sex (P = 0.003), lymph node involvement in metachronous cancer (P < 0.001), pathological invasive size of metachronous cancer >15 mm (P < 0.001) and overlapping squamous cell carcinoma histology of the initial and metachronous cancers (P = 0.003) were significant prognostic factors for poor survival after the second resection, whereas histological IPM was not (P = 0.065). Surgery for cN0 metachronous lung cancer is safe and shows good outcomes. There were no statistically significant differences in the SPLC and IPM results. Caution should be exercised when operating on patients with overlapping squamous cell carcinoma.

Global Cervical Cancer Incidence by Histological Subtype and Implications for Screening Methods

BackgroundCervical cancer is a major global health concern, disproportionately affecting women in developing countries. Cervical cancer has two primary subtypes, squamous cell carcinoma (SCC) and adenocarcinoma (AC), each with distinct characteristics and screening effectiveness. In this study, we aimed to estimate the global incidence of cervical cancer according to histological subtype to inform prevention strategies.MethodsUsing data from population-based cancer registries, we computed the rates of SCC, AC, and other specified histology among all cervical cancer cases by country and by 5-year age group. Proportions were subsequently applied to the estimated number of cervical cancer cases from the Global Cancer Observatory 2020. Age-standardized incidence rates were calculated.ResultsSCC accounted for 82.72% of global cervical cancer cases, with AC contributing 12.18%. The highest SCC incidence was in Sub-Saharan Africa (29.79 per 100,000 population). The AC incidence was highest in South-Eastern Asia (3.67 per 100,000 population). Age-specific trends showed SCC peaking at approximately age 55 years and AC plateauing after age 45 years.ConclusionsThis study provided a comprehensive estimate of cervical cancer incidence by histological subtype. SCC remained the dominant subtype globally, whereas the incidence of AC varied across regions. These findings highlighted the need for tailored prevention strategies, especially testing for human papillomavirus to detect AC in high burden areas.

Comparison of Survival Between Different Histological Subtypes in Cervical Cancer Patients: A Retrospective and Propensity Score-matched Analysis.

Objective: To investigate the correlation between different histological subtypes (adenosquamous carcinoma, adenocarcinoma, and squamous cell carcinoma) and the prognosis of cervical cancer. Materials and Methods: In this retrospective cohort analysis, patients with cervical cancer who underwent radical surgery followed by either concurrent chemoradiotherapy (CCRT) or radiotherapy (RT) at West China Hospital of Sichuan University between 2009 and 2018 were enrolled. The study included patients with confirmed pathological diagnoses of cervical adenosquamous carcinoma (ASC), adenocarcinoma (AC), and squamous cell carcinoma (SCC). To ensure a balanced representation, 1:3 propensity score matching (PSM) between cervical adenosquamous carcinoma (ASC) or adenocarcinoma (AC) and squamous cell carcinoma (SCC) was performed. The prognosis of different pathological subtypes, including 5-year overall survival (OS), 5-year disease-free survival (DFS), and treatment failure patterns in terms of recurrence and metastasis, were evaluated between groups. Results: This study enrolled a total of 714 patients between 2009 and 2018, of whom 614 (86%) were diagnosed with SCC. In a 1:3 ratio propensity score matching, 34 cases of ASC were matched with 102 cases of SCC, while 66 cases of AC were paired with another 198 cases of SCC. Baseline demographic and disease characteristics were well-balanced among the treatment groups. During a median follow-up period of 41 months (range: 14 to 122 months), a total of 40 patients experienced disease recurrence. The primary recurrence pattern was distant metastasis, observed in 36 out of 40 cases. Among these cases, recurrence occurred in 28 patients (9.3%) diagnosed with SCC, 10 patients (15.2%) with AC, and 2 patients (5.9%) with ASC. In the AC group, local failure and distant failure were observed in 2% and 12% of cases, respectively. In comparison, the corresponding rates in the paired SCC group were 0.6% and 8.7%. The 5-year OS and DFS rates in the AC group were 82.1% and 79.2%, respectively, compared to the paired SCC group, which had rates of 95.2% and 92.8% respectively (p<0.05). Conversely, in the ASC group, the 5-year OS and DFS rates were 96.3% and 92.6%, while the paired SCC group displayed OS and DFS rates of 93.4% and 81.2% respectively, with no statistically significant difference observed. Conclusions: By comparing the prognostic outcomes of different histological subtypes, we concluded that AC histology was linked to a poor prognosis and an increased risk of distant recurrence. ASC histology had a similar outcome to SCC histology rather than AC. Given the poor prognosis for patients diagnosed with AC after adjusting for prognostic factors, it becomes imperative to explore alternative treatment options beyond the current conventional therapy for this condition.

Twenty-five-year mortality trends of four major histological subtypes of cervical cancer: a population-based study using the Osaka cancer registry data

ObjectiveTo assess the mortality trends of four major histological subtypes of cervical cancer diagnosed between 1994 and 2018.MethodsThis population-based retrospective cohort study was conducted using the Osaka Cancer Registry data from 1994 to 2018. A total of 12,003 patients with cervical cancer, squamous cell carcinoma (SCC), adenocarcinoma (A), adenosquamous cell carcinoma (AS), or small cell neuroendocrine carcinoma (SCNEC) were identified. Patients were classified into groups according to the extent of disease (localized, regional, or distant), year of diagnosis (1994–2002, 2003–2010, or 2011–2018), and histological subtype (SCC, A/AS, or SCNEC). Then, their survival rates were assessed using univariate and multivariate analyses.ResultsOverall, improved survival rates were observed according to the year of diagnosis in patients with local, regional, and distant cervical cancers. When examined according to the histological subtypes, improved survival rates according to the year of diagnosis were observed in patients with local, regional, and distant SCCs and in those with local and regional A/AS. In patients with distant A/AS, the survival rates did not improve since 2003. In patients with cervical cancer with SCNEC, the survival rates did not improve since 1994 irrespective of the extent of the disease. In the multivariate analysis, non-SCC histology was found to be an independent prognostic factor for OS.ConclusionIn contrast to SCC histology associated with improved survival between 1994 and 2018, SCNEC histology and advanced (stage IVB) A/AS remain to be the unmet medical needs for the management of cervical cancer.

The effect of platelet-to-lymphocyte ratıo (PLR) and glasgow prognostıc score (GPS) on recurrence, and survıval ın patıents undergoıng lobectomy for early-stage non-small cell lung cancer (NSCLC).

Tumor markers are indicators that can be used not only for cancer diagnosis but also for determining prognosis. Unfortunately, there is currently no tumor marker that reliably predicts the prognosis of lung cancer. In this study, we investigated the prognostic impact of the platelet-to-lymphocyte ratio (PLR) and Glasgow Prognostic Score (GPS), known as inflammation markers in peripheral blood, in patients who underwent resection for early-stage non-small cell lung cancer (NSCLC). We retrospectively analyzed the medical records of a total of 3300 patients who underwent surgery for NSCLC between 2010 and 2020. Among these patients, 250 met the inclusion criteria of lobectomy, pT1-T2N0 stage, and histology of adenocarcinoma or squamous cell carcinoma. Preoperative albumin, C-reactive protein (CRP), preoperative PLR, and postoperative 5th-day PLR values were determined from patient's peripheral blood data. The impact of these values on postoperative recurrence and survival was investigated. GPS was calculated based on preoperative CRP and albumin values, and patients were divided into 3 groups: 0 (mild), 1 (moderate), and 2 (severe). The relationship between preoperative GPS and survival was analysed. Among the included patients, 155 (62%) had adenocarcinoma and 95 (38%) had squamous cell carcinoma. A total of 185 (74%) patients had pT1 tumors, while 65 (26%) had pT2 tumors. During the postoperative follow-up period, local recurrence was observed in 28 (11.2%) patients and distant metastasis in 51 (20.4%) patients. The overall mortality rate was 19.6%. The 5-year survival rates for pT1 and pT2 tumors were 80.4% and 72.5%, respectively. Significant associations were found between preoperative PLR, postoperative PLR, and recurrence (p = 0.005 and p = 0.011). The expected overall survival (OS) was 103.4months in the mild GPS group, 91.8months in the moderate GPS group, and 50months in the severe GPS group. The relationship between GPS groups and OS was statistically significant (p = 0.005). Preoperative analysis of PLR and GPS may provide prognostic value in NSCLC patients who undergo surgical resection. Our study provides a rationale for further investigation of peripheral blood immune markers for prognostic purposes.

Positive factors on survival of head and neck cancer of unknown primary: what the clinician can do

Background Management of patients with head and neck cancer of unknown primary (HNCUP) is challenging. Aims/Objectives To provide a long-term analysis focusing on protective survival factors for clinical decision-making. Furthermore, the prognostic value of the current N classification system was evaluated. Material and methods We retrospectively analyzed patients with HNCUP between 2003 and 2016. Univariate and multivariate analyses were used to investigate predictors of overall survival (OS). Results A primary tumor was found in 67 of 290 patients with suspected HNCUP, leaving after exclusion 141 HNCUP cases for analysis, who received multi-step therapy (MST) (n = 108) or single therapy (n = 28). Chemotherapy (CT) (n = 101), curative MST, ≤3 positive lymph nodes (LN) (n = 33), squamous cell carcinoma (SCC) (n = 123), HPV+ (n = 21), M0 (n = 70) increased OS by 21.8%, 24.4%, 12.7%, 6.8%, 18.7%, 29.6%, respectively. 5- and 10-year OS was 78.1%/66.6%. The number of metastatic LNs predicted OS is better than N classification. Conclusion and significance Aspects for clinical decision-making: Curative MST and SCC histology were the most significant predictors for improved OS. Categorizing LN into 1, 2-3, and >3 LNs was more significant than the traditional N classification. The addition of CT to curative MST has a stronger impact on survival than HPV and N classifications.

Is Programmed Death Ligand 1(PD-L1) Expression in Vulvar Cancer Prognostic for Locoregional Control?

Vulvar cancer is a rare female genital neoplasm in which surgery and radiotherapy play an integral role in the treatment paradigm; however, locoregional recurrence remains the predominant pattern of failure. Little is known about the impact of PD-L1 status in vulvar cancer and its value for clinical outcomes and response prediction to immunotherapy. We sought to explore clinical outcomes of patients with positive PD-L1 expression in vulvar cancer. Single-institution retrospective analysis of patients with surgically resectable invasive vulvar carcinoma from 2001-2021 was performed. Patients with locally advanced disease not amendable to upfront surgery or de novo metastatic disease were excluded. Immunohistochemical PD-L1 expression was assessed using the Combined Positive Score (CPS) with positive expression defined as ≥1, and Tumor Proportion Score (TPS) with positive expression defined as ≥1%. Survival and disease control outcomes were calculated using the Kaplan-Meier Method with log-rank t-test. Multivariable analysis was conducted using a parsimonious cox regression analysis using forward conditional selection. A total of 85 patients were identified with a median age of 69 years old (IQR: 59-78), 54% (n = 46) FIGO stage I-II, 97% (n = 82) squamous cell carcinoma histology, 41% (n = 35) p16 positive status, 74% (n = 63) without a history of lichen sclerosis, 40% (n = 34) without co-existing vulvar intraepithelial neoplasm (VIN), and 49% (n = 42) treated with surgery alone. There were 72% (n = 61) with positive PD-L1 TPS (≥1%), and 81% (n = 69) with positive PD-L1 CPS (≥1) expression. The median follow up was 49 months (IQR: 21-75 months). The 5-year OS was 79% (95% CI, 70%-89%), DFS 55% (95% CI, 43%-67%), local control (LC) 59% (95% CI, 47%-72%), regional control (RC) 86% (95% CI, 78%-94%), and distant metastasis (DM) 96% (95% CI, 92%-100%). PD-L1 expression was associated with lower LC and DFS by TPS ≥1%. The 5-year LC of 82% (95% CI, 65%-98%) for PD-L1 negative versus 50% (95% CI, 34%-65%) positive disease (p = 0.03). The 5-year DFS was 77% (95% CI, 59%-95%) for PD-L1 negative versus 46% (95% CI, 31%-61%) positive disease (p = 0.03). No significant DFS or LC difference was noted by CPS levels ≥1. No significant difference was observed for RC, DM, or OS. On multivariable analysis, PD-L1 TPS remained a significant predictor for LC (HR = 3.01, 95% CI, 1.07-8.95, p = 0.04). No significant difference in DFS was observed for PD-L1 TPS on multivariable analysis. PD-L1 expression is associated with higher rates of local recurrence and may represents a potentially important actionable target independent of p16 status to improve the predominant pattern of relapse in this uncommon malignancy.

Image-Guided High-Dose-Rate Brachytherapy for Definitive Management of Primary Vaginal Cancer: A Single Institutional Experience

To assess the safety and efficacy of image-guided high-dose-rate brachytherapy (IGBT) alone or in combination with external beam radiation therapy (EBRT) for the treatment of vaginal cancers. The study analyzed patients diagnosed with primary vaginal cancers from 2004 to 2021 who received definitive radiotherapy at a single institution. Interstitial implants were performed using a freehand technique and transvaginal or transrectal-ultrasound for imaging guidance. IGBT was planned using inverse planning simulated annealing (IPSA) software. Data collected and analyzed included patient and tumor characteristics, dose and fractionation, and treatment outcomes. Complications were assessed using CTCAEv4 scores, and descriptive and survival analyses were performed using R-studio. Sixty-six patients met inclusion criteria. Patients were staged as I (14), II (23), III (19), and IV (10) based on revised FIGO 2018 staging. 47 (72%) had squamous cell carcinoma histology, and median age was 65 years. The most common regimen was 45 Gy in 25 fractions of EBRT followed by IGBT boost of 18 Gy in 3 fractions with 1 implant (n = 40). For melanoma, an IGBT boost of 19 Gy in 2 fractions with a single implant was used (n = 7). For IGBT monotherapy, the most common regimen was 36 Gy in 6 fractions delivered over 2 implants (n = 3). 41 (66%) of the patients received systemic therapy. Local failures occurred in 8 (12%) patients, while 8 (12%) developed distant metastases. Median overall survival was 64.7 months. Overall survival was 64.3% (95% CI 51.9-79.7%) at 3 years, and 50.9% (95% CI 35.7-72.5%) at 5 years. Grade 3 or 4 toxicities were reported in 4 (6%) patients including vaginal fistula (n = 3) and urethral stricture (n = 1). The results suggest that utilizing IGBT for freehand interstitial implants in combination with EBRT is a safe and effective primary treatment for vaginal cancer, with durable local control and low toxicity. Further research is needed to establish multi-institutional practice patterns and recommendations.

Patterns of Adaptive Replanning in Proton Therapy for Thoracic Malignancies

Theability to deliver high doses of localized radiation therapy (RT) while preferentially sparing surrounding normal tissue makes the use of proton beam therapy (PBT) advantageous for thoracic malignancies. However, these traits also make PBT more susceptible to treatment related changes to the tumor or target volume, patient anatomy or surrounding tissue. This may result in increased need for adaptive re-planning during PBT. We present a single institution experience examining patterns of PBT adaptive re-planning in patients treated for thoracic malignancies. Consecutive patients treated with PBT for thoracic malignancies from 2017-2022 at an academic proton center were retrospectively analyzed. Patients were treated with intensity modulated proton therapy (IMPT) either once or twice daily (BID), with or without concurrent systemic therapy. Patients with lung and thymic malignancies were included. Quality assurance CT (QACT) scans were assessed for dosimetric changes. Number and frequency of QACTs was determined by departmental policy and clinical factors such as histology, cancer stage and concurrent systemic therapy. Statistical comparisons of the frequency of replans and pathological and patient characteristics were performed with two-tailed Fisher's exact tests and Chi-Square tests. Of the 340 patients who were retrospectively analyzed, 80 (24%) required replanning during treatment. Median age was 67 years (range 20-89) and 49 (61%) patients were men. Median radiation dose was 59.5 Gy (range 16.2 -70 Gy). Pathology requiring replan included small cell lung cancer (n = 6, 8%), lung adenocarcinoma (n = 23, 29%), lung squamous cell carcinoma (n = 25, 31%), mesothelioma (n = 7, 9%), thymic malignancy (n = 5, 6%) or other histology (n = 10, 13%). 46 (58%) patients received concurrent systemic or chemotherapy. Six (8%) patients were treated in a BID approach. Histology, frequency of treatment, and concurrent systemic treatment were not significant predictors of patients requiring replan. Of the 80 total patients that required replanning, a total of 122 replans were completed. A total of 360 quality assurance CT (QACT) scans were used for all replans. Sixty (75%) patients required only one re-plan, 20 (25%) required two or more re-plans. Median number of treatments prior to the initial replan was 13 treatments (range 2 -41). Reason for requiring replanning included change in tumor size (n = 21), change in anatomy (n = 41, 51%), concern for toxicity (n = 4, 5%), change to radiation plan (n = 2, 3%), or technical/technique related changes (n = 12, 15%). Our single institution experience highlights the need for adaptive replanning in patients with thoracic malignancies treated with PBT to ensure adequate target coverage and to help spare normal tissue.