Squamous Cell Carcinoma Histology Research Articles

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.

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.

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.

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.

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.

The Spectrum of HPV-independent Penile Intraepithelial Neoplasia: A Proposal for Subclassification.

Compared with vulva, precursor lesions of human papillomavirus (HPV)-independent invasive squamous cell carcinoma (SCC) of the penis are insufficiently characterized. We analyzed the histologic and immunohistochemical characteristics of 70 peritumoral precursor lesions and correlated them with the histology and mutational profile of the adjacent HPV-negative invasive penile SCC. Atypical basal keratinocyte proliferation with variously elongated epithelial rete with premature squamatiziation, but regular superficial cornification, termed differentiated penile intraepithelial neoplasia (d-PeIN), were identified adjacent to 42/70 (60%) SCC (36/42 keratinizing (P<0.001); 3 papillary, and 1 each verrucous, clear cell, sarcomatoid SCC). d-PeIN were associated with chronic inflammatory dermatoses (32/42; P<0.001), p53 overexpression (26/42; P<0.001), and hotspot mutations in TP53 (32/42; P<0.001), CDKN2A (26/42; P<0.001) or both (21/42; P=0.003) in the adjacent SCC. Cytoplasmic p16ink4a overexpression in 5/42 d-PeIN correlated with CDKN2A missense mutations in the adjacent SCC. In all, 21/70 (30%) cornified verrucous or glycogenated verruciform precursors with minimal atypia and wild-type p53 (18/21; P<0.001) occurred adjacent to verrucous or papillary SCC (17/21; P<0.001) and keratinizing (4/21) SCC, which harbored mutations in HRAS and/or PIK3CA (12/21; P<0.004). Undifferentiated p16ink4a-negative full-thickness precursors were identified in 7/70 (10%) SCC. Four histologically different HPV-independent penile precursor lesions can be assigned to 2 major genetic/biological pathways with characteristic highly differentiated precursors requiring different clinical management decisions. These include d-PeIN in chronic inflammatory dermatoses, with p53 overexpression and TP53/CDKN2A mutations, and the p53 wild-type verrucous and verruciform precursors unassociated with dermatoses, but with mutations in oncogenes PIK3CA and HRAS.

Detection of early (T1) lung cancers and lepidic adenocarcinomas in sputum and bronchial cytology

BackgroundThe lung is an extensively epithelialized organ, producing ample exfoliated material for sputum and bronchial cytology. In view of the updates in the World Health Organization classification of early (T1/≤ 3 cm) lung cancer with respect to adenocarcinomas with lepidic pattern, this study retrospectively reviews sputum and bronchial cytology paired with resection-confirmed lung cancers. MethodsA computerized search for all lung resection specimens of carcinomas over a 20-year period was performed. Cytologic diagnoses of corresponding sputum and bronchial cytology were classified into five-tiered categories (C1-insufficient/inadequate, C2-benign, C3-atypia, C4-suspicious and C5-malignant). Reports and slides of the resection specimen were reviewed for reclassification of T1 cancers. ResultsTotally 472 and 383 sputum and bronchial cytology specimens respectively were included. Sensitivity for T1 lesions on sputum cytology were 10.6 %, 2.1 % and 0.5 % at cutoffs of atypia/C3, suspicious/C4 and malignant/C5 categories, lower than bronchial cytology (35.1 %, 15.5 %, 8.1 %; p < 0.001). T1 lesions correlated with lower detection rates, whereas squamous cell carcinoma histology, larger size and bronchial invasion were associated with increased detection rates in sputum and bronchial cytology (p < 0.050). Detection rates for abrasive bronchial cytology (brushing) were overall higher (p = 0.018- < 0.001), but on subgroup comparison, non-abrasive (aspiration, lavage and washing) cytology demonstrated favorable trends (p = 0.063–0.088) in detecting T1 lesions. Adenocarcinomas with lepidic pattern had lower suspicious/C4 (p = 0.040) or above and malignant/C5 (p = 0.019), but not atypia/C3 or above (p = 0.517) rates. ConclusionsMost adenocarcinomas with lepidic pattern are only diagnosed as atypia/C3 on cytology. With its modest sensitivity, interpretation of negative and indeterminate cytology results mandates caution.

Machine-Learning-Aided Prediction of Brain Metastases Development in Non–Small-Cell Lung Cancers

PurposeNon–small-cell lung cancer (NSCLC) shows a high incidence of brain metastases (BM). Early detection is crucial to improve clinical prospects. We trained and validated classifier models to identify patients with a high risk of developing BM, as they could potentially benefit from surveillance brain MRI. MethodsConsecutive patients with an initial diagnosis of NSCLC from January 2011 to April 2019 and an in-house chest-CT scan (staging) were retrospectively recruited at a German lung cancer center. Brain imaging was performed at initial diagnosis and in case of neurological symptoms (follow-up). Subjects lost to follow-up or still alive without BM at the data cut-off point (12/2020) were excluded. Covariates included clinical and/or 3D-radiomics-features of the primary tumor from staging chest-CT. Four machine learning models for prediction (80/20 training) were compared. Gini Importance and SHAP were used as measures of importance; sensitivity, specificity, area under the precision-recall curve, and Matthew's Correlation Coefficient as evaluation metrics. ResultsThree hundred and ninety-five patients compromised the clinical cohort. Predictive models based on clinical features offered the best performance (tuned to maximize recall: sensitivity∼70%, specificity∼60%). Radiomics features failed to provide sufficient information, likely due to the heterogeneity of imaging data. Adenocarcinoma histology, lymph node invasion, and histological tumor grade were positively correlated with the prediction of BM, age, and squamous cell carcinoma histology were negatively correlated. A subgroup discovery analysis identified 2 candidate patient subpopulations appearing to present a higher risk of BM (female patients + adenocarcinoma histology, adenocarcinoma patients + no other distant metastases). ConclusionAnalysis of the importance of input features suggests that the models are learning the relevant relationships between clinical features/development of BM. A higher number of samples is to be prioritized to improve performance. Employed prospectively at initial diagnosis, such models can help select high-risk subgroups for surveillance brain MRI.

The Effect of Nasogastric Feeding after Surgery in Patients with Head and Neck Cancers – Retrospective Single Center Experience

This study aimed to assess clinical factors that could predict the need for nasogastric feeding after surgery in patients with head and neck cancer (HNC) and evaluate the effect of tube feeding on selected laboratory parameters. This single-center retrospective study included 153 patients who underwent surgery for HNC. Data on patient and tumor characteristics were collected, along with laboratory measurements. Logistic regression was used to identify the predictors of the need for nasogastric feeding. Laboratory parameters were compared between patients who required nasogastric feeding vs those who did not. Nasogastric feeding was required in 90 patients (59%). Significant predictors of nasogastric feeding in HNC patients after surgery, which were revealed by univariate regression analysis, included low body mass index (odds ratio [OR] = 0.84), squamous cell carcinoma histology (OR = 8.05), T2 tumor stage (OR = 2.27), red blood cell count (M/µL) (OR = 0.44), hemoglobin levels (g/dL) (OR = 0.80), and mean corpuscular volume (fL) (OR = 1.10). Multivariate analysis showed that low BMI (OR = 0.87) and red blood cell count (M/µL) (OR = 0.32) were prognostic factors for nasogastric feeding. A significant percentage increase in white blood cell count from admission to discharge was noted in patients who required nasogastric feeding vs those who did not (p = 0.003). Determining factors that predict the need for nasogastric feeding in HNC patients after surgery may support more personalized treatment planning to optimize clinical outcomes.

Prognostic Impact of the Immune-Cell Infiltrate in N1-Positive Non–Small-Cell Lung Cancer

IntroductionThe tumoral immune milieu plays a crucial role for the development of non–small-cell lung cancer (NSCLC) and may influence individual prognosis. We analyzed the predictive role of immune cell infiltrates after curative lung cancer surgery. Materials and MethodsThe tumoral immune-cell infiltrate from 174 patients with pN1 NSCLC and adjuvant chemotherapy was characterized using immunofluorescence staining. The density and distribution of specific immune cells in tumor center (TU), invasive front (IF) and normal tissue (NORM) were correlated with clinical parameters and survival data. ResultsTumor specific survival (TSS) of all patients was 69.9% at 5 years. The density of tumor infiltrating lymphocytes (TIL) was higher in TU and IF than in NORM. High TIL density in TU (low vs. high: 62.0% vs. 86.7%; p = .011) and the presence of cytotoxic T-Lymphocytes (CTLs) in TU and IF were associated with improved TSS (positive vs. negative: 90.6% vs. 64.7% p = .024). High TIL-density correlated with programmed death-ligand 1 expression levels ≥50% (p < .001). Multivariate analysis identified accumulation of TIL (p = .016) and low Treg density (p = .003) in TU as negative prognostic predictors in squamous cell carcinoma (p = .025), whereas M1-like tumor- associated macrophages (p = .019) and high programmed death-ligand 1 status (p = .038) were associated with better survival in adenocarcinoma. ConclusionThe assessment of specific intratumoral immune cells may serve as a prognostic predictor in pN1 NSCLC. However differences were observed related to adenocarcinoma or squamous cell carcinoma histology. Prospective assessment of the immune-cell infiltrate and further clarification of its prognostic relevance could assist patient selection for upcoming perioperative immunotherapies.