Stage IVA Disease Research Articles

Validation of the 2021 FIGO vulvar cancer staging schema (567)

Objectives: The International Federation of Gynecology and Obstetrics (FIGO) revised the cancer staging schema of vulvar cancer in 2021. Major changes to stage III-IV diseases included: (i) prior stage IIIA-B diseases were re-classified based on nodal size (<5mm for stage IIIA vs >5mm for stage IIIB), and (ii) prior stage IVA1 disease based on non-osseous organ extension was re-classified to stage IIIA. This study sought to validate the 2021 FIGO vulvar cancer staging schema. Methods: This retrospective cohort study examined 889 women with stage III-IV vulvar cancer from 2010-2015 in the Surveillance, Epidemiology, and End Results Program. Stage-shift and overall survival (OS) were assessed, comparing the 2021 and 2009 FIGO staging schemas. Results: Stage-shift occurred in 229 (25.8%) cases: upstaging in stage IIIA (54.1%), downstaging in stage IIIB (7.5%), and downstaging in stage IVA (45.3%) diseases. When comparing the new and prior staging schemas, 5-year OS rates were 45.6% versus 48.9% for stage IIIA, 47.0% versus 44.2% for stage IIIB, and 13.9% versus 25.1% (interval change: -11.2%) for stage IVA disease. According to the revised staging schema, 5-year OS rates were similar between stage IVA and IVB diseases (13.9% vs 14.5%, p=0.221) and between stage IIIA and IIIB disease (45.6% vs 47.0%, p=0.997). For new stage IIIA disease, 5-year OS rates differed significantly based on the staging factors (nodal involvement vs non-nodal organ involvement, 48.9% vs 38.7%, difference 10.2%, p=0.038). Conclusions: The 2021 FIGO staging schema is useful to distinguish survival in advanced vulvar cancer. Survival of new stage IVA disease appears to be comparable to stage IVB disease. Survival of new stage IIIA disease is heterogeneous based on the nodal versus non-nodal organ involvements. Objectives: The International Federation of Gynecology and Obstetrics (FIGO) revised the cancer staging schema of vulvar cancer in 2021. Major changes to stage III-IV diseases included: (i) prior stage IIIA-B diseases were re-classified based on nodal size (<5mm for stage IIIA vs >5mm for stage IIIB), and (ii) prior stage IVA1 disease based on non-osseous organ extension was re-classified to stage IIIA. This study sought to validate the 2021 FIGO vulvar cancer staging schema. Methods: This retrospective cohort study examined 889 women with stage III-IV vulvar cancer from 2010-2015 in the Surveillance, Epidemiology, and End Results Program. Stage-shift and overall survival (OS) were assessed, comparing the 2021 and 2009 FIGO staging schemas. Results: Stage-shift occurred in 229 (25.8%) cases: upstaging in stage IIIA (54.1%), downstaging in stage IIIB (7.5%), and downstaging in stage IVA (45.3%) diseases. When comparing the new and prior staging schemas, 5-year OS rates were 45.6% versus 48.9% for stage IIIA, 47.0% versus 44.2% for stage IIIB, and 13.9% versus 25.1% (interval change: -11.2%) for stage IVA disease. According to the revised staging schema, 5-year OS rates were similar between stage IVA and IVB diseases (13.9% vs 14.5%, p=0.221) and between stage IIIA and IIIB disease (45.6% vs 47.0%, p=0.997). For new stage IIIA disease, 5-year OS rates differed significantly based on the staging factors (nodal involvement vs non-nodal organ involvement, 48.9% vs 38.7%, difference 10.2%, p=0.038). Conclusions: The 2021 FIGO staging schema is useful to distinguish survival in advanced vulvar cancer. Survival of new stage IVA disease appears to be comparable to stage IVB disease. Survival of new stage IIIA disease is heterogeneous based on the nodal versus non-nodal organ involvements.

HIPEC after neoadjuvant chemotherapy is associated with acceptable toxicity and favorable quality of life in newly diagnosed advanced ovarian cancer patients (509)

HIPEC after neoadjuvant chemotherapy is associated with acceptable toxicity and favorable quality of life in newly diagnosed advanced ovarian cancer patients (509)

Efficacy and tolerability of a low dose weekly paclitaxel, carboplatin, cetuximab (PCC) regimen for metastatic or unresectable head and neck squamous cell carcinomas.

e18019 Background: The standard of care for metastatic or unresectable head and neck squamous cell cancers (HNSCCs) is 5-FU and a platinum doublet with cetuximab or pembrolizumab. However, these regimens are cumbersome as they involve hospitalization for continuous 5-FU infusion and carry a high toxicity profile. In addition, many patients are unfit for this regimen due to poor performance status (PS) or comorbidities. An alternative is paclitaxel, carboplatin, and cetuximab (PCC). PCC has been shown to be a promising induction regimen in small, mostly retrospective studies. Also, low dose chemotherapy may improve tolerability. Our study evaluates the tolerability and efficacy of low dose PCC with or without concurrent palliative radiation therapy (RT) in patients with metastatic or unresectable HNSCCs. Methods: This retrospective observational study included 40 patients with metastatic or unresectable HNSCCs at a single academic center who received PCC between August 2017 and January 2022. Included patients were not candidates for standard frontline therapies due to either PS, comorbidities, prior progression on these therapies, plan for RT, or patient preference. Chart review was performed to grade adverse events (AEs) according to CTCAE criteria. Progression free survival (PFS), overall survival (OS), and response to treatment were assessed per RECIST 1.1 guidelines. Results: Of the 40 patients, mean age was 69.6 years (SD 15.4), and 82.5% were male. Common primary sites were oral (13, 32.5%), oropharynx (12, 30%), hypopharynx (4, 10%), and sinus (4, 10%). Most patients had Stage IVa disease (16, 40%) followed by IVc (12, 30%) and IVb (6, 15%). The remainder (6, 15%) had stage III or unknown stage. Patients received weekly paclitaxel (30-50 mg/m2), carboplatin (AUC 1.5-2), and cetuximab 400 mg/m2 loading followed by 250 mg/m2 maintenance dose. 8 patients (20%) received concurrent RT. Most were treated with palliative intent (32, 80%) and a few induction intent (8, 20%). Prior to PCC, 11 patients had prior salvage surgery, 19 prior RT, and 18 prior systemic therapy. Baseline ECOG PS was 0-2 in 37 patients (92.5%). The most common AEs were skin rash (27, 67.5%), fatigue (22, 55%), and mucositis (12, 30%). 7 patients (17.5%) experienced a grade 3-4 AE, which were mostly hematologic. 2 of the 8 patients on concurrent RT experienced a grade 3-4 AE. 5 patients (12.5%) stopped PCC treatment due to toxicities. 8 patients (20%) had progression on initial follow up imaging. Median duration of response was 4.3 months. PFS was 7.8 months. Median OS was 19.2 months. Conclusions: Our study supports the use of PCC in metastatic or unresectable HNSCCs. This regimen can be considered in patients with suboptimal PS who are not candidates for standard frontline therapies or for those planned for palliative RT. PCC can be used safely and effectively with or without concurrent RT.

Metronomic systemic PCm (paclitaxel, carboplatin + metronomic) neoadjuvant chemotherapy in head and neck cancer.

e18073 Background: Neoadjuvant chemotherapy (NACT) in head and neck cancers (HNC) with taxane, platinum, 5-FU (TPF) regimen is both toxic as well as difficult to use in resource-constrained settings. We used a novel combination of weekly chemotherapy and oral metronomic chemotherapy (OMCT) and assessed the efficacy and safety of this combination as NACT in locally advanced HNC patients. Methods: This is a retrospective analysis of prospectively maintained data. 56 patients with technically unresectable HNC received NACT with paclitaxel (80mg/m2) plus carboplatin (AUC2) - weekly schedule and OMCT (methotrexate 9mg/m2 once a week, celecoxib 200mg twice daily, and erlotinib 150mg once daily) - PCm regimen. Patients were assessed clinically and radiologically after a minimum of six cycles for resectability. The radiological response was evaluated as per RECIST 1.1. We report the response rate, resectability, survival, and tolerance of this NACT regimen. Results: The median age of the patients was 41 years. Fifty-two patients (92.9%) were male. Buccal mucosa (60.7%) and oral tongue (17.9%) were the commonest sites of primary seen followed by alveolus (10.7%), the floor of mouth (5.4%), and larynx (5.4%). AJCC 2017 stage IVA and IVB disease were present in 64.3% and 35.7% of patients respectively. Edema up to zygoma (44.6%), high ITF involvement (19.7%), technically unresectable nodal disease (16.1%) and disease reaching up to vallecula (12.5%), or hyoid bone (5.4%), and nodal encasement (180-270 degree) of the internal carotid artery (1.8%) were the reasons for technical unresectability. The median number of NACT administered was six. The tumor showed partial response in 54 (96.4%) patients, 2 (3.6%) patients had stable disease and none of the patients had tumor progression. Surgery was planned in 47 (83.9%) patients after NACT, however due to logistic issues only 35 (62.5%) patients could undergo surgery. Pathological complete response was seen in 27 (48.21%) patients. After a median follow-up of 7.36 months, median PFS was not reached in the whole cohort and surgery group of patients, whereas it was 5.23 (95% CI, 4.08 -6.38) months in the non-surgery group. Median OS was not reached in our cohort. Common grade 3/4 toxicities (CTCAE 5.0) observed were oral mucositis in 6 (10.7%) patients, diarrhea in 4 (7.1%), and febrile neutropenia in 1 (1.7%) patients. Conclusions: Weekly scheduled PCm is an efficacious and well-tolerated regimen and can easily be administered in resource-constrained settings.

Trends in guideline-adherent chemoradiation therapy for locally advanced cervical cancer before and after the affordable care act

ObjectiveTo assess trends in guideline-adherent chemoradiation therapy (GA-CRT) for locally advanced cervical cancer relative to Patient Protection and Affordable Care Act (ACA) implementation. MethodsNational Cancer Database patients treated with chemoradiation for locally advanced cervical cancer (FIGO 2018 Stage IB3-IVA) from 2004 to 2016 were included. GA-CRT was defined according to NCCN guidelines and included: 1) delivery of external beam radiation, 2) brachytherapy, and 3) chemotherapy, 4) no radical hysterectomy. Logistic regression was used to determine trends in GA-CRT relative to the ACA. Survival was also estimated using Kaplan-Meier analysis. Results37,772 patients met inclusion criteria (Pre-ACA:16,169; Post-ACA:21,673). A total of 33,116 patients had squamous cell carcinoma and 4626 patients had other histologies. Forty-five percent of patients had lymph node-positive disease. A total of 14.6% of patients had Stage I disease, 41.8% had Stage II disease, 36.4% had Stage III disease, and 7.9% had Stage IVA disease. On multivariable analysis, medicare insurance (OR 0.91; 95%CI: 0.84–0.99 compared to commercial insurance), non-squamous histology (OR 0.83; 95%CI: 0.77–0.89 for adenocarcinoma) and increasing Charlson-Deyo score were associated with decreased odds of receiving GA care. Increasing T-stage was associated with greater receipt of GA-CRT. The percentage of the population that received guideline adherent care increased post-ACA (Pre-ACA 28%; Post-ACA 34%; p < 0.001). Adherence to treatment guidelines increased 2-year survival by 15% (GA 76%; Not GA 61%; p < 0.001). Increased 2-year survival was seen in the post-ACA cohort (Pre-ACA 62%; Post-ACA 69%; p < 0.001). ConclusionsImplementation of the ACA was associated with improved GA-CRT and survival in patients with locally advanced cervical cancer.

Development and Validation of a Decision Analytical Model for Posttreatment Surveillance for Patients With Oropharyngeal Carcinoma

Clinical practice regarding posttreatment radiologic surveillance for patients with oropharyngeal carcinoma (OPC) is neither adapted to individual patient risk nor fully evidence based. To construct a microsimulation model for posttreatment OPC progression and use it to optimize surveillance strategies while accounting for both tumor stage and human papillomavirus (HPV) status. In this decision analytical modeling study, a Markov model of 3-year posttreatment patient trajectories was created. The training data source was the American College of Surgeon's National Cancer Database from 2010 to 2015. The external validation data set was the 2016 International Collaboration on Oropharyngeal Cancer Network for Staging (ICON-S) study. Training data comprised 2159 patients with OPC treated with primary radiotherapy who had known HPV status and disease staging information. Patients with American Joint Committee on Cancer, 7th edition stage III to IVB disease and those with clinical metastases during the time of primary treatment were included. Data were analyzed from August 1 to October 31, 2020. Main outcomes included disease stage and HPV status, specific disease transition probabilities, and latency of surveillance regimens, defined as time between recurrence incidence and disease discovery. Training data consisted of 2159 total patients (1708 men [79.1%]; median age, 59.6 years [range, 40-90 years]; 401 with stage III disease, 1415 with stage IVA disease, and 343 with stage IVB disease). Cohorts predominantly had HPV-negative disease (1606 [74.4%]). With model-optimized regimens, recurrent disease was discovered a mean of 0.6 months (95% CI, 0.5-0.8 months) earlier than with a standard surveillance regimen based on current clinical guidelines. Recurrent disease was discovered using the optimized regimens without significant reduction in sensitivity. Compared with strategies based on reimbursement guidelines, the model-optimized regimens found disease a mean of 1.8 months (95% CI, 1.3-2.3 months) earlier. Optimized, risk-stratified surveillance regimens consistently outperformed nonoptimized strategies. These gains were obtained without requiring any additional imaging studies. This approach to risk-stratified surveillance optimization is generalizable to a broad range of tumor types and risk factors.

Reduced FEV1 as Prognostic Factors in Patients With Advanced NSCLC Receiving Immune Checkpoint Inhibitors.

BackgroundThe aim of study is to investigate the influence of pulmonary function on the prognosis in patients with advanced non-small cell lung cancer (NSCLC) receiving immune checkpoint inhibitors (ICI).Patients and MethodsData were collected retrospectively from 151 patients with stage IV NSCLC who received ICI and completed spirometry before ICI therapy in Taipei Veterans General Hospital between January 2016 and December 2020. The co-primary end points were overall survival (OS) and progression-free survival (PFS) between groups divided by 80% predicted FEV1 since ICI therapy started; the secondary outcomes were objective response rate.ResultsAmong 151 patients enrolled to this study, 67.5% of patients were men, 75.5% were adenocarcinoma, 24.5% had known targetable driver mutation, 33.8% received first-line ICI, and 62.8% received ICI monotherapy. The objective response rate was 24.5% and disease control rate was 54.3%. In multivariable analysis, patient with reduced FEV1 had inferior PFS (FEV1 < 80% vs. FEV1 ≥ 80%, adjusted HR = 1.80, P = 0.006) and OS (FEV1 < 80% vs. FEV1 ≥ 80%, adjusted HR = 2.50, P < 0.001). Median PFS and OS in the preserved FEV1 group (≥80% predicted FEV1) compared to the reduced FEV1 group (<80% predicted FEV1) were 5.4 vs. 2.9 months (HR = 1.76, P = 0.003) and 34.9 vs. 11.1 months (HR = 2.44, P < 0.001), respectively. The other independent prognostic factors of OS include stage IVA disease (adjusted HR = 0.57, P = 0.037), initial liver metastasis (adjusted HR = 2.00, P = 0.049), ICI monotherapy (adjusted HR = 1.73, P = 0.042) and ICI related pneumonitis (adjusted HR = 3 .44, P = 0.025).ConclusionsReduced FEV1 is strongly associated with inferior clinical outcomes in patients with advanced NSCLC treated with ICI.

Geriatric assessment and treatment outcomes in a Dutch cohort of older patients with potentially curable esophageal cancer

Background Patients with potentially curable esophageal cancer can be treated with neo-adjuvant chemoradiotherapy followed by surgery or definitive chemoradiotherapy with curative intent. For frail older patients choosing the appropriate oncological treatment can be difficult, and data on geriatric deficits as determinants of treatment outcomes are not yet available. Objectives To describe the prevalence of geriatric deficits and to study their association with treatment discontinuation and mortality in older patients with potentially curable esophageal cancer. Material and Methods A cohort study was conducted in a Dutch tertiary care hospital including patients aged ≥70 years with primary stage I-IVA esophageal cancer. Geriatric screening and assessment data were collected. Outcomes were treatment discontinuation and one year all-cause mortality. Results In total, 138 patients with curable esophageal cancer were included. Mean age was 76.1 years (standard deviation 4.7), 54% had clinical stage III and 24% stage IVA disease. Most patients received neo-adjuvant chemoradiotherapy and surgery (41%), 32% definitive chemoradiotherapy and 22% palliative radiotherapy. Overall, one year all-cause mortality was 36%. Geriatric screening and assessment was performed in 94 out of 138 patients, of which 60% was malnourished, 20% dependent in Instrumental Activities of Daily Living (IADL) and 52% was frail. Malnutrition was associated with higher mortality risk (Hazard Ratio, 3.2; 95% Confidence Interval, 1.3–7.7)) independent of age, sex and tumor stage. Seventy-six out of 94 patients were treated with chemoradiotherapy, of which 23% discontinued treatment. Patients with IADL dependency and Charlson Comorbidity Index ≥1 discontinued treatment more often. Conclusion All-cause mortality within one year was high, irrespective of treatment modality. Treatment discontinuation rate was high, especially in patients treated with definitive chemoradiotherapy. Geriatric assessment associates with outcomes in older patients with esophageal cancer and may inform treatment decisions and optimization in future patients, but more research is needed to establish its predictive value. Trial registration: The study is retrospectively registered at the Netherlands Trial Register (NTR), trial number NL8107. Date of registration: 22-10-2019.

Residual tumor and primary debulking surgery vs interval debulking surgery in stage IV epithelial ovarian cancer.

It is debated whether women with FIGO (International Federation of Gynecology and Obstetrics) Stage IV epithelial ovarian cancer should be offered primary debulking surgery (PDS) or interval debulking surgery (IDS). Furthermore, the impact of complete resection of intra-abdominal disease (R0) despite their extra-abdominal metastases is questioned. The objective of this study was to investigate the impact of intra-abdominal residual tumor, Stage IVA vs IVB, the localization and number of metastases defining Stage IV disease on overall survival (OS) comparing PDS and IDS in FIGO Stage IV epithelial ovarian cancer. We included 2091 women registered with Stage IIIC-IV ovarian cancer in the Danish Gynecological Cancer Database during 2009-2016. The impact of residual tumor was evaluated using univariate and multivariate analyses. In total, 681 patients had stage IV disease, of whom 26% underwent PDS, 38% IDS, and 36% chemotherapy only. Overall survival for PDS and IDS were similar. Patients achieving R0 at PDS showed a tendency towards a higher OS than patients achieving R0 at IDS, though the difference was non-significant. In women with Stage IVA and IVB disease there was a survival benefit in achieving R0 both when treated with PDS and IDS. Women with Stage IVB disease treated with chemotherapy only had a significantly lower OS than patients achieving R0 at both PDS and IDS. Malignant pleural effusion and having five metastatic sites compared with having one was associated with a poorer OS. Our study shows similar OS in patients with Stage IV disease treated with IDS compared with PDS. Complete intra-abdominal tumor resection improves the prognosis in both PDS and IDS in Stage IV ovarian cancer. Malignant pleural effusion seems to be a negative prognostic factor and should have more focus in future studies.

Diagnostic characteristics, treatment patterns, and clinical outcomes for patients with advanced/metastatic medullary thyroid cancer

BackgroundMedullary thyroid cancer (MTC) accounts for approximately 1.6% of new cases of thyroid cancer. The objective of this study was to describe patient characteristics, biomarker testing, treatment patterns, and clinical outcomes among patients with advanced/metastatic MTC in a real-world setting in the United States and to identify potential gaps in the care of these patients.MethodsSelected oncologists retrospectively reviewed medical records of patients aged ≥ 12 years diagnosed with advanced MTC. Patients must have initiated ≥ 1 line of systemic treatment for advanced/metastatic MTC between January 2013–December 2018 to be eligible. Patient characteristics, biomarker testing, and treatment patterns were summarized descriptively; progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method.ResultsThe 203 patients included in this study had a mean (SD) age of 52.2 (10.4) years; mean (SD) duration of follow-up from start of first-line treatment was 24.5 (16.0) months. Most patients (82.8%) were initially diagnosed with stage IVA, IVB, or IVC disease. Among all patients, 121 (59.6%) had testing for RET mutations, of whom 37.2% had RET-mutant MTC. The RET-mutation type was reported for 28 patients; the most common mutations reported were M918T (64.3%) and C634R (32.1%). Of the 203 patients, 75.9% received only one line of systemic treatment for advanced disease, and 36% were still undergoing first-line therapy at the time of data extraction. Cabozantinib (30.0%), vandetanib (30.0%), sorafenib (17.2%), and lenvatinib (4.9%) were the most common first-line treatments. Among 49 patients who received second-line treatment, most received cabozantinib (22.4%), vandetanib (20.4%), lenvatinib (12.2%), or sunitinib (12.2%). Median PFS (95% confidence interval [CI]) from start of first- and second-line treatments was 26.6 months (20.8–60.8) and 15.3 months (6.6-not estimable [NE]), respectively. Median OS from initiation of first- and second-line treatment was 63.8 months (46.3-NE) and 22.4 months (12.4-NE), respectively.ConclusionsFor the treatment of advanced/metastatic MTC, no specific preference of sequencing systemic agents was observed in the first- and second-line settings. Considering the recent approval of selective RET inhibitors for patients with RET-mutant MTC, future research should investigate how treatment patterns evolve for these patients.

Validation of the 2021 FIGO staging schema for advanced vulvar cancer

ObjectiveThe International Federation of Gynecology and Obstetrics (FIGO) revised the vulvar cancer staging schema in 2021. Previous stage IIIA–B diseases were reclassified based on nodal size (≤5 mm for stage...

Swallowing Function Following Neoadjuvant Chemotherapy and Transoral Robotic Surgery for Oropharyngeal Carcinoma: A 2-Year Follow-up.

To evaluate 2-year follow-up swallowing function in patients with human papillomavirus-related oropharyngeal squamous cell carcinoma (HPV+ OPSCC) who completed neoadjuvant chemotherapy and transoral robotic surgery (NAC+S). Retrospective analysis of patients with OPSCC treated with NAC+S between 2010 and 2021. A single academic institution. This is a cross-sectional study of patient-reported swallowing function, assessed with the MD Anderson Dysphagia Inventory (MDADI) at least 2 years after completion of treatment. The inclusion criteria are patients with HPV+ OPSCC who underwent NAC+S at least 2 years ago. Those requiring adjuvant radiation or chemoradiation or experiencing relapse were excluded from the study. Completed MDADIs were received from 37 patients at a median 3.8 years posttreatment (interquartile range, 2.0-8.6 years). Of those, 94.6% (n = 35) were male and 81.1% (n = 30) were White. The median age at OPSCC diagnosis was 59.0 years (interquartile range, 41-80 years). The most frequent primary subsite of OPSCC was the base of the tongue (n = 20, 54.1%), followed by the tonsils (n = 16, 43.2%). In addition, 75.7% (n = 28) had stage IVa disease (TNM seventh edition), and 29 (78.4%) had scores ≥80, classified as optimal function. When compared with patients who received bilateral neck dissection, patients who received unilateral neck dissection were associated with an age <65 years old (P = .036) and lower clinical TNM stage (P = .04), as well as higher composite, emotional, functional, and physical MDADI scores (P = .017, .046, .013, and .05, respectively). Patients with OPSCC who were treated with NAC+S achieved satisfactory long-term swallowing outcomes. Unilateral neck dissection was significantly associated with higher MDADI scores in this patient cohort.

Hypofractionated Low-Dose Total Skin Electron Beam Therapy for Primary Cutaneous T-Cell Lymphoma: Analysis of Efficacy and Toxicity

▪IntroductionCutaneous T-cell lymphoma (CTCL) is a rare form of lymphoma that is characterized by the localization of malignant cells to the skin. While considerable advances have been made in both the diagnosis and treatment of this disease, management and long-term disease control continue to be significant challenges. In particular, total skin electron beam therapy (TSEBT)-a technique that allows for homogenous irradiation of the entire skin-has proved to be efficacious for palliatively treating CTCL (Heumann TR et al IJROBP 2015), but a large proportion of patients continue to relapse over time with a limited possibility of retreatment due to skin toxicity (Wilson LD et al J Am Acad Dermatol 1996; Becker M et al IJROBP 1995).Recently, low-dose TSEBT to ~12 Gy has largely replaced traditional TSEBT to ~36 Gy for the palliative treatment of CTCL due to similar high response rate with less toxicity and more room to re-treat as necessary (Hoppe et al J Am Acad Dermatol 2015). However, there is little consensus on the optimal fractionation and dose per fraction (i.e. number of total treatments needed to deliver 12 Gy).At our institution, we have implemented a novel condensed hypofractionated scheme for low-dose TSEBT, where instead of giving ½ cycle (3 positions) per fraction, we give a full cycle (all 6 positions) per fraction, leading to half as many treatments (6 instead of 12) for the same total dose (12 Gy). We hypothesize that condensed low-dose TSEBT given in 6 fractions, compared to 12, will have similar toxicity and efficacy with the additional convenience of half as many treatments.MethodsWe conducted a single-institution retrospective review of patients with primary CTCL who received TSEBT at UT Southwestern between 2012 and 2021. We stratified patients based on whether they received high-dose TSEBT (18 Gy or above) or low-dose TSEBT (12 Gy), and among those with low-dose TSEBT substratified them between standard fractionation (12 fractions) or hypofractionation (6 fractions). We recorded each patient's primary outcomes, which included response to radiation (complete response, near complete response, partial response, stable disease, or progressive disease), time to response, duration of response, and any acute toxicities. Physician-assessed secondary outcomes, demographic information, and any systemic treatments given concurrently or adjuvantly with TSEBT were also included.ResultsOverall, 46 patients received 59 courses of TSEBT, with 39 patients receiving 52 courses of low-dose TSEBT. Of the 52 low-dose courses evaluated, median age at treatment was 62.5 years old (range, 21-91). Most patients had stage IB, IIB, or IVA disease before initiation of TSEBT. The overall response rate was 87%. Nine courses (17%) resulted in a complete response, 5 courses (9.6%) resulted in a near complete response, and 25 courses (48%) resulted in a partial response. The incidence of progression of skin disease was 17% at 6 months and 21% at 1 year.Of the 59 total courses, 40 patients had hypofractionation (full cycle) and 8 patients had standard fractionation (half cycle). There was no significant difference in the response rate between these two groups.The median time to response for the hypofractionation compared to the standard fractionation was 7 weeks versus 8.5 weeks, respectively, while the duration of response was 46 weeks versus 54 weeks, respectively. Concurrent treatments included bexarotene for 2 patients, brentuximab for 2 patients, interferon for 1 patient, and romidepsin for 1 patient. Importantly, no patients experienced significant toxicities including those in the hypofractionation group, with the exception of 1 patient (2.5%) who experienced grade 3 desquamation.ConclusionIn the largest series to date of low-dose TSEBT using a hypofractionation scheme, our results suggest that it is equally safe and effective as traditional fractionation. This novel condensed low-dose TSEBT comes with the added benefits of convenience and cost-effectiveness, as well as decreased patient exposure to the healthcare system during the current pandemic, and should be considered for all CTCL patients needing TSEBT. Moving forward, we look to evaluate the impact of radiation therapy with concurrent or adjuvant treatments for patients with CTCL as alternative options for possibly supplementing the efficacy of radiotherapy and/or reducing the need for recurrent radiation altogether. DisclosuresDesai: Boston Scientific: Consultancy, Research Funding.

Factors predicting the perineural invasion in carcinoma oral cavity.

This study to evaluate clinicopathological parameters such as age, tumor location, tumor size, grade, depth of invasion (DOI), lymphovascular space invasion (LVSI), lymph node metastasis, and stage that predict peri-neural invasion (PNI) in oral squamous cell carcinoma (OSCC). A retrospective study on 1716 postoperative OSCC patients who satisfied the eligibility criteria and treated from January 2009 to December 2019 was analyzed using IBM SPSS V23. Mean and percentage were assessed using descriptive statistics. Wilcoxon-Mann-Whitney U-test was used to compare continuous variables, while Chi-square test was used to compare discrete variables between PNI-positive and PNI-negative groups. Two-tailed P < 0.05 was considered to be statistically significant. Out of 1716 patients, 553 were PNI positive. The mean age was 48.76 ± 12.42 years in PNI-positive patients while 51.52 ± 12.51 years in PNI-negative patients. Males outnumbered females. The most common primary was carcinoma buccal mucosa (204, 36.9%), followed by carcinoma of oral tongue (161,29.1%). Maximum tumor size was 3.14 ± 1.20 cm in PNI-positive patients whereas 2.78 ± 1.22 cm in PNI-negative patients. Sixty (10.84%) patients in PNI-positive group and 51 (4.38%) in PNI-negative group had LVSI positive. Lymph node involvement was observed in 305 (55.13%) patients in PNI-positive group whereas 358 (30.78%) patients in PNI-negative group. Maximum number 228 (41.3%) in PNI-positive patients were in Stage IVA disease. PNI is one of the important adverse prognostic factors having a definite correlation with anatomical subsite, tumor size, grade, DOI, LVSI, lymph node involvement, and stage of the disease. PNI should be analyzed in postoperative histopathology report of OSCC that guides the clinician for adjuvant therapy.

MA17.01 Reduced FEV1 as Prognostic Factors in Patients With Advanced NSCLC Receiving Immune Checkpoint Inhibitors

The impact of reduced pulmonary function on patients with non-small cell lung cancer (NSCLC) receiving immune checkpoint inhibitors (ICI) is not fully elucidated. The aim of study is to investigate the influence of pulmonary function on the prognosis and treatment outcome in advanced NSCLC patients receiving ICI. Data were collected retrospectively from 151 patients with stage IV NSCLC who received ICI and completed spirometry before ICI therapy in Taipei Veterans General Hospital between January 2016 and December 2020. The co-primary end points were overall survival (OS) and progression-free survival (PFS) between groups divided by 80% predicted FEV1 since ICI therapy started; the secondary outcomes were objective response rate. Among 151 patients enrolled to this study, 67.5% of patients were men, 75.5% were adenocarcinoma, 24.5% had known targetable driver mutation, 33.8% received first-line ICI, and 62.8% received ICI monotherapy. The objective response rate was 24.5% and disease control rate was 54.3%. In multivariable analysis, patient with reduced FEV1 had inferior PFS (50%≤ FEV1< 80% vs. FEV1≥80%, adjusted HR= 1.67; 30%≤ FEV1< 50% vs. FEV1≥80%, adjusted HR= 1.822, FEV1< 30% vs. FEV1≥ 80%, adjusted HR= 10.39, P=0.003), and OS (50%≤ FEV1<80% vs. FEV1≥ 80%, adjusted HR= 2.10; 30%≤ FEV1< 50% vs. FEV1≥ 80%, adjusted HR= 3.43; FEV1< 30% vs. FEV1≥ 80%, adjusted HR= 14.41, P<0.001). Median PFS and OS in the preserved FEV1 group (≥80% predicted FEV1) compared to the reduced FEV1 group (<80% predicted FEV1) were 5.4 vs. 2.9 months (adjusted HR= 1.80, P=0.006) and 34.9 vs. 11.1 months (adjusted HR=2.50, P<0.001), respectively. The other independent prognostic factors of OS include stage IVA disease (adjusted HR= 0.56, P=0.032), initial liver metastasis (adjusted HR= 2.15, P=0.030), and ICI monotherapy. (adjusted HR= 1.73, P=0.042)View Large Image Figure ViewerDownload Hi-res image Download (PPT) Reduced FEV1 is strongly associated with inferior clinical outcomes in patients with advanced NSCLC treated with ICI.

Is Hyperthermic Intrathoracic Chemotherapy (HITHOC) Safe and Efficacious in Masaoka-Koga Stage-IVA Thymoma? A Pilot Study.

This study was aimed at evaluating the safety and efficacy of hyperthermic intrathoracic chemotherapy in patients with Masaoka stage IVA thymoma. This is a retrospective comparative analysis between two groups of patients who were operated for Masaoka stage IVA thymoma. One group underwent complete parietal pleurectomy whereas other group received hyperthermic intrathoracic chemotherapy after complete pleurectomy. An analysis of all perioperative variables, complications and survival was carried out. A total of 13 patients had stage IVA disease during the study period. Initial 7 patients (March 2012-March 2015) underwent complete parietal pleurectomy, whereas next 6 patients (April 2015-December 2018) had undergone HITHOC after complete parietal pleurectomy. Both groups are comparable in terms of age, co-morbidities, tumor size and duration of symptoms. The duration of surgery and intra-operative blood loss, postoperative ICU stay, duration of ICD and total hospital stay was similar between two groups. The total number of post-operative complications was higher in HITHOC group (5 vs 2), however non-significant (p = 0.10). The median follow-up duration was 63months in no HITHOC group and 49.5months in HITHOC group. There was no peri-operative mortality. The overall survival (P = 0.06) and relapse-free survival (P = 0.36) were not significantly different in the both groups. Hyperthermic intrathoracic chemotherapy is a safe and feasible modality with no added morbidity or mortality. Multi-institutional prospective studies with large number of patients are required to accurately assess survival benefit.

Superior Vena Cava Reconstruction in Masaoka Stage III and IVa Thymic Epithelial Tumors

BackgroundWe present here a case series of patients who underwent resection for Masaoka stage III and IVa thymic epithelial tumors (TETs) with invasion into the superior vena cava (SVC). MethodsA total of 29 patients with stage III and IVa TETs were treated surgically in 3 institutions. Operative resections involved replacing the SVC from one of the innominate veins (n = 18) or via reconstruction by truncal replacement (n = 2) or patch plasty (n = 9). ResultsFifteen patients underwent neoadjuvant treatment. Thirty- and 90-day mortality rates were 3.4% and 10.3%, respectively. For stage III patients, the median overall survival and disease-free survival (DFS) were 39 and 30 months, respectively. The median overall survival and DFS in patients with Masaoka stage IVa disease were 67 and 21 months, respectively. Undergoing only preoperative chemotherapy (P = .007) or receiving no chemotherapy (P = .009) had a DFS that was significantly higher than receiving both preoperative and postoperative chemotherapy. ConclusionsSVC resection and reconstruction in Masoaka stage III and IVa TETs can be performed with acceptable morbidity and mortality. Stage IVa patients with SVC involvement can be treated with similar results as stage III patients with multimodality treatment.

Association of Primary Treatment Modality for Advanced-Stage Oropharyngeal Squamous Cell Carcinoma With Survival Outcomes

Definitive chemoradiotherapy and upfront surgical treatment are both accepted as the standard of care for advanced-stage oropharyngeal squamous cell carcinoma. However, the optimal primary treatment modality remains unclear. To evaluate the comparative effectiveness of definitive chemoradiotherapy and upfront surgical treatment for advanced-stage oropharyngeal cancer. This retrospective comparative effectiveness analysis used data from the population-based Taiwan Cancer Registry. Included patients were diagnosed with clinical stage III or IV oropharyngeal squamous cell carcinoma from 2007 to 2015 and were identified from the registry. Patients with T4b or N3 disease were excluded. Data were analyzed from June 2019 through December 2020. Definitive chemoradiotherapy or upfront surgical treatment. The primary outcome was overall survival, for which data were available through December 31, 2018. Secondary outcomes were progression-free survival, locoregional recurrence-free survival, and distant metastasis-free survival. Among 1180 patients, 694 patients (58.8%) were in the definitive chemoradiotherapy group and 486 patients (41.2%) were in the upfront surgical treatment group. The median (interquartile range) follow-up was 3.62 (1.63-5.47) years, and most patients were men (1052 [89.1%] men) with a primary tumor in the tonsils (712 patients [60.3%]), moderately differentiated histology (604 patients [51.2%]), clinical N2 disease (858 patients [72.7%]), and clinical stage IVA disease (938 patients [79.5%]). The mean (SD) age was 54.59 (10.35) years. Primary treatment with an upfront surgical procedure was associated with a decreased risk of death during the study period (hazard ratio [HR], 0.81; 95% CI, 0.69-0.97; P = .02). However, when adjusted for age, subsite, histological grade, and T and N classification, upfront surgical treatment was no longer associated with an increased risk of death during the study period (HR, 0.96; 95% CI, 0.80-1.16; P = .70). Progression-free survival was worse in the group receiving upfront surgical treatment than in the group receiving chemoradiotherapy (HR, 1.64; 95% CI, 1.09-2.46; P = .02), and this difference persisted after adjusting for other factors associated with prognosis (ie, age, tumor subsite, histological grade, and T and N classification) (HR, 1.72; 95% CI, 1.12-2.66; P = .01). This study found that definitive chemoradiotherapy was associated with effectiveness that was comparable with that of upfront surgical treatment when adjusted for baseline factors associated with prognosis. These findings suggest that definitive chemoradiotherapy should be considered to avoid accumulating toxic effects associated with surgical treatment and chemoradiotherapy.

Outcome of neoadjuvant chemotherapy (NACT) with paclitaxel plus carboplatin and oral metronomic chemotherapy (OMCT) in patients with technically unresectable oral cavity squamous cell carcinoma (SCC).

e18034 Background: NACT is often used in technically unresectable oral cavity SCC to improve resection rate. NACT regimen based on combination of maximum tolerated doses (MTD) and metronomic chemotherapy will debulk the tumor and subsequently inhibit angiogenesis which may overcome drug resistance of MTD schedule. We assessed outcome and tolerance of this combination as NACT in patients with technically unresectable oral cavity SCC. Methods: This is retrospective analysis of prospectively maintained data. Fourteen patients having technically unresectable oral cavity SCC received NACT with paclitaxel (175mg/m2) plus carboplatin (AUC5) every 3 weekly (MTD schedule) and OMCT (methotrexate 9mg/m2 once a week, celecoxib 200mg twice daily and erlotinib 150mg once daily). Patient were assessed clinically and radiologically after minimum of two cycles for surgery. Kaplan-Meier method was used for survival analysis. We report resectability, survival and tolerance of this regimen. Results: Median age of the patients was 38 years, and twelve patients (85%) were male. Twelve (85%) and two (15%) patients had buccal mucosa and oral tongue primary, respectively. AJCC 2017 stage IVA and IVB disease was present in twelve (85%) and two (15%) patients, respectively. Reason for technical unresectabilty was skin edema above zygoma in five (36%), high infratemporal fossa involvement in five (36%), nodal encasement of major vessels in two (14%) and posterior extent of oral tongue tumor into oropharynx in two (14%) patients. Median number of NACT administered were three. Tumor of nine patients (65%; 95% CI = 39%-89%) were deemed resectable after NACT. Eight patients underwent surgery and tumor of one patient showed pathologic complete response. Median follow up was 14.6 months (95% CI = 14.1 - 15 months). Median progression free survival was 11.4 months (95% CI = 7.9 – 15 months). Median overall survival (OS) was not reached while OS at 15 months was 63.5% (95% CI = 37.8% - 89.2%). Common grade 3/4 toxicities (CTCAE 5.0) were neutropenia in eight (57%), thrombocytopenia in three (21%), febrile neutropenia, hypokalemia and diarrhoea in two patients (14%) each. Two patients required in-patient supportive care for adverse events. Conclusions: Paclitaxel and carboplatin along with OMCT is well tolerated and less resource intensive regimen which leads to favorable resection rate and survival in patients with technically unresectable oral cavity SCC.

Effect of neoadjuvant systemic therapy given during window trials on quality metrics in resectable head and neck squamous cell carcinoma.

6033 Background: Quality oncologic care, including negative surgical margin status, adequate lymph node yield and prompt initiation of adjuvant treatment, impacts disease control and overall survival in patients with mucosal head and neck squamous cell carcinoma (HNSCC). The aim of this study was to ascertain the effect of neoadjuvant systemic therapy given during window trials on oncologic quality metrics in patients with delayed definitive surgery for a HNSCC. Methods: Treatment-naïve patients with HNSCC participating in one of two window of opportunity clinical trials at UPMC from 2009-2019 were included. Neoadjuvant regimens consisted of one dose of cetuximab (n = 33) or anti-ErbB3 antibody (n = 9) within 28 days of surgery. Sociodemographic, clinical and tumor staging were recorded. The primary outcome was overall oncologic quality, as defined as a composite measure of negative margin status, adequate lymph node yield, completion of adjuvant therapy (if indicated) and time to initiation of adjuvant therapy within 6 weeks of surgery. Secondary outcomes were difference in clinical and pathologic stages and overall survival (OS). Results: A total of 42 patients with a mean age of 57.1 (±10.2) years and median follow-up of 58 months were analyzed. 29 patients had clinical stage IVA disease with 43% (18/42) oral cavity, 36% (15/42) larynx/hypopharynx and 21% (9/42) oropharynx primaries. All patients underwent surgery following neoadjuvant systemic therapy. In 30 patients (71%), all oncologic quality markers were achieved. Pathological downstaging occurred in 21% (9/42) of patients with 4 patients no longer meeting criteria for adjuvant treatment and were observed. 3 patients showed pathological upstaging. The 3-year OS were 76% (95% CI of 63.6-88.4), respectively. Patients with a pathologic downstage migration (64.9%, 95% CI of 49.9-79.8) had higher 5-year OS compared to those without (57.8%, 95% CI of 40.1-76.4, P = 0.046). Conclusions: Most patients receiving neoadjuvant systemic therapy on window trials prior to surgery met all oncologic quality markers. Importantly, even with brief window trial therapy pathologic downstaging was achieved and associated with significantly better overall survival.