T4 Disease Research Articles

The Failure Patterns of Nasopharygeal Carcinoma After Intensity-Modulated Radiotherapy and Implications for Surveillance.

ObjectiveTo investigate the treatment outcomes, failure patterns and surveillance strategy in patients with nasopharyngeal carcinoma (NPC) after intensity-modulated radiotherapy (IMRT).MethodsA cohort of patients with NPC who had received the full course of IMRT between 2008 and 2012 were retrospectively analyzed. The failure patterns, time to recurrence, and detection methods were recorded. The survival was calculated using the Kaplan–Meier method. Multivariate proportional hazard regression models were used to test the prognostic factors.ResultsIn total, 2607 patients with NPC treated with IMRT were recruited. After the median follow-up of 112 months, 402 (15.4%) patients experienced distant metastasis, 225 (8.6%) patients had local recurrence, and 77 (3.0%) patients had regional recurrences. The 10-year overall survival (OS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) rates were 74.5%, 90.1%, and 79.3%, respectively. The factors of male sex, age >50 years, lactate dehydrogenase >245 IU/L, advanced T classification, and advanced N classification were associated with poor OS. The N disease classification was the most important factor in predicting distant metastasis, and advanced T disease classification for high risk of local recurrence. For patients with T1 disease, the incidence of local recurrence was less than 2%, and the incidence of distant metastasis was less than 5% for patients with N0 disease. About 83% of the recurrence occurred in the first 5 years, and 20% of the recurrences showed no symptoms.ConclusionHigh rate of local-regional control can be achieved for patients with NPC after IMRT, while distant metastasis remains as the major cause of failures. Patients with advanced N classification has high risk to develop distant metastasis, and most occurred within 5 years. Developing rational and individualized surveillance strategies based on the high risk factors of recurrence is helpful to balance the survival benefit and medical cost.

Surgical challenges and considerations in Tri-modal therapy for muscle invasive bladder cancer.

Trimodal therapy (TMT) for muscle invasive bladder cancer has become an accepted alternative to radical cystectomy and has become integrated into national guidelines as standard a treatment option. The urologist plays a critical role in proper patient selection, thorough transurethral resection, ongoing cystoscopic surveillance and management of local recurrences. There exists multiple patient related and tumor related factors, which contribute to the selection of TMT vs. radical cystectomy for a patient with muscle invasive bladder cancer. Although the ideal patient for TMT has a tumor which can undergo a visibly complete resection, has no associated hydronephrosis, does not invade the prostatic urethra and is not associated with diffuse carcinoma in situ throughout the bladder, select patients who do not meet all these criteria can still be successfully treated with this approach. A multidisciplinary approach including urology, radiation oncology and medical oncology is paramount with clear communication of tumor location, timing of chemoradiation and repeat cystoscopic resection followed by surveillance. Nonmuscle invasive bladder cancer recurrences can occur in up to 26% of patients after completion of TMT, with many being treated by routine and standard therapy for non-muscle invasive bladder cancer. However, in this population after TMT, early salvage cystectomy should be considered in those with adverse features, including T1 disease, tumor greater than 3 cm, CIS, or lymphovascular invasion. Salvage cystectomy can be performed for local recurrences with acceptable oncologic control and no clear evidence of any greater risk of early complications; however, there may be a slightly increased risk for late complications, namely small bowel obstruction, ureteral stricture, and parastomal hernia. An understanding of these surgical considerations is of utmost importance to the treating urologist in selecting and managing a patient through TMT.

585. INDIAN SINGLE CENTRE EXPERIENCE USING CROSS PROTOL IN CARCINOMA ESOPHAGUS AND GASTROESOPHAGEAL JUNCTION (GEJ)

Abstract Last decade has changed the treatment modality in esophageal cancer. Neoadjuvant chemoradiation followed by surgery is proven to be highly effective in locally advanced esophageal and GEJ tumors by Dutch CROSS protocol. The aim of neoadjuvant treatment is to increase R0 resection, down staging and pathological complete response which eventually increases disease free and overall survival. This is a prospective observational single arm study of 51 patients who were treated with neoadjuvant chemoradiation with radiation therapy (RT) to 41.4 Gy/23 Fr/4.5 weeks and weekly paclitaxel and carboplatin, followed by surgery at our institute between 2013 and 2021. Eligibility for the use of CROSS protocol was expanded beyond the clinical stage T1N1 or T2-3N0-1, which includes T4aN0-1, T3N2-3. The median age of this cohort was 58 years. 37/51 (72%) had T3 disease, 8/51 (15%) had T4a and 14/51 (27%) had N2/N3 disease. 90% patients had squamous cell carcinoma. All patients completed the intended dose of radiation; 11/51 (22%) patients had a treatment delay due to haematological toxicity; one patient died. 42 (82%) successfully completed esophagectomy with R0; one patient had inoperable disease, four defaulted and three refused surgery; 26 (62%) had pCR, 12 (28.57%) PR and one had SD. At last follow up 35 patients were alive, 12 died of disease and 7 had recurrent disease. Our experience of neoadjuvant chemo radiation therapy (CROSS protocol) is in line with published data. Surgery post induction therapy was not associated with increased morbidity. It was associated with high complete resections and pathological complete response.

Minimum number of necessary lymph nodes for the accurate staging of adenocarcinoma of esophagogastric junction

ObjectiveThis study aims to explore the minimum number of lymph nodes (LNs) necessary for assessing the postoperative staging of adenocarcinoma of esophagogastric junction (AEG). MethodsWe extracted the data of patients from the Surveillance Epidemiology and End Results (SEER) database, who were pathologically diagnosed with AEG between 2000 and 2017. We explored the associations between the number of LNs and overall survival (OS) by univariate and multivariate analyses and determined the proper cutoff value of the number of LNs necessary for accurate postoperative staging. ResultsOf the patients with AEG in the SEER database, 2668 met our inclusion criteria. The total number of regional LNs dissected was found to be significantly associated with survival in analyses stratified by T stage. Univariate and multivariate regression showed that age, grade, positive LNs, number of LNs examined, and T stage were independently associated with OS. For patients with T1-2 tumors, the 5-year survival rate was 58.7%, and patients with more than 11 LNs examined obtained a greater survival benefit. Among patients with T3-4 tumors, the 5-year survival rates were 28.9% and 39.7% for those with 1–16 LNs examined and for those with more than 17 LNs examined, respectively. ConclusionTo accurately determine the pathological stage of patients with AEG, no less than 11 LNs must be resected for patients with stage T1-2 disease, and no less than 16 LNs must be resected for patients with stage T3-4 disease.

Outcomes With Optimal Treatment in Geriatric Head and Neck Cancers – Tertiary Cancer Centre Experience

Aim: Older patients with locally advanced head and neck cancers (LA-HNC) are under-represented in clinical trials and denied standard treatment with concurrent Chemo-radiation. Most are treated with Radiotherapy (RT) alone. However, with the use of Intensity Modulated Radiation Therapy (IMRT) and good supportive care, even this cohort of patients can be considered for chemo-radiation. Methods and Materials: 69 patients with age >65 years with LA-HNC treated between April 2015 and December 2019 in our Institute were prospectively evaluated for treatment compliance and outcomes. All patients were planned to receive 70Gy in 33-35 fractions with IMRT and weekly Cisplatin at a dose of 40mg/m2 (or Carboplatin-AUC-2). Loco-regional Control (LRC), Overall survival (OS) and prognostic factors were evaluated. Results: Median age at presentation was 67 years (65-81). 54 were male. 64% had Karnofsky Performance Status of >90. 42% had Oropharyngeal Primary. 17% had co-morbidities. 66% had T3 disease, 77% had Node positive disease. 54% had stage III disease. All patients completed 70Gy. 81% patients received at least 5 (>200mg/m2) chemotherapy cycles. Acute Grade3 toxicity was seen in 20% of patients. 64% had complete response. With a median follow up of 23.6 months (3-71), OS was 53.5%. Estimated 2-year LRC was 60%; estimated 2- and 5-year OS was 53.5% and 34.3% respectively. On Univariate analysis, age <70 years, Cisplatin use, limited nodal disease, Stage III and complete response to treatment showed good OS (p<0.05). Conclusion: Definitive chemo-IMRT approach in older LA-HNC is well tolerated with good clinical outcomes. Hence older age should not be a barrier for standard treatment.

20 A Novel Case of Metastatic Hypopharyngeal Carcinoma Without Nodal Involvement

Abstract Introduction In the UK, patients with hypopharyngeal carcinoma are managed via a multidisciplinary team approach based on UK National MDT Guidelines. Hypopharyngeal cancer often presents late, 80% of patients presenting with Stage III or IV disease, with PET-CT recommended for these patients to assess for metastases. Aim To report a novel case of an elderly ex-smoker with hypopharyngeal carcinoma without nodal involvement. Method An 86-year-old ex-smoker presented to the otolaryngology department with a T2N0 hypopharyngeal carcinoma, which was later upstaged to T3N0M1 following a PET-CT scan. Results & Conclusions This case highlights discrepancies between the MDT Guidelines and NICE guidance over when to perform staging scans. NICE recommends PET-CT for T4 or N3 disease compared to Stage III or IV disease in the National MDT guidelines. Our patient would not have qualified for PET-CT under NICE guidance and his metastatic disease would have been undiagnosed. This case highlights that lack of nodal involvement does not exclude metastases and there should be a low index of suspicion for distant metastases in patients with significant systemic symptoms.

Lymph node ratio predicts overall survival in patients with stage II non-small cell lung cancer: a population-based SEER analysis

BackgroundIn non-small-cell lung cancer (NSCLC), there are many factors that affect prognosis, and the lymph node ratio (LNR) may play a significant role. Our study aimed to confirm the value of the LNR in the prognosis of patients with stage II NSCLC.MethodsPatient data were obtained from the Surveillance, Epidemiology and End Results (SEER) database. The classification for the LNR was best determined using the X-tile method. The correlation between the LNR and overall survival (OS) was validated after the Kaplan–Meier analysis was performed. To determine the correlation between the LNR and survival, stratification and the Cox regression analysis were used.ResultsIn our study, 14,183 stage II NSCLC patients were included. Among them, 8303 patients had N1 disease. According to the X-tile analysis, the optimal critical points for the LNR in N1 patients with NSCLC was 0.21 and 0.38. We categorized the cohorts as low (LNR-L ≤ 0.21; n = 5158, 62.1%), medium (0.21 < LNR-M ≤ 0.38; n = 1736, 20.9%), and high (LNR-H > 0.38; n = 1409, 17.0%). According to the Kaplan–Meier analysis, the patients with a high LNR were considerably worse than those with a medium or low LNR (P < 0.001), which was also proven by stratified and multivariate analyses. The value of the LNR was reflected in all the subgroup analyses, especially in patients ages < 60 years. The multivariate competing risks regression analysis revealed that younger age, female sex, T1 disease, adenocarcinoma and N0 disease was associated with a better prognosis after controlling for potential confounders (P < 0.001).ConclusionsFor patients with stage II NSCLC, the LNR is valuable for assessing prognosis. A higher LNR indicates a worse prognosis.

Implementation of a dedicated head and neck radiotherapy peer review conference: results of a prospective study

Background Head and neck radiotherapy (RT) is complex, involving multiple targets and organs at risk (OARs). Routine RT plan peer review is often inadequate for thorough review of the head and neck targets and OARs. Methods Patients treated between August 2020 and December 2021 were evaluated in a weekly structured head and neck RT plan peer review conference including at least one head and neck RT subspecialist. Patient and disease factors were recorded, as were the results of the peer review discussion, including the number and nature of recommended RT plan modifications and the rate of implementation. A major change was defined as any modification to the high-dose planning target volume (PTV) or RT prescription or fractionation. A minor change was defined as modification to at least one of the intermediate-dose PTV, low-dose PTV, or any OAR. Results 186 patients treated by 8 individual providers were prospectively recorded, 86.6% from the main site and 13.4% from 3 regional practices. The most common primary sites were oropharynx (29.6%), oral cavity (22%), cutaneous (16.7%), larynx/hypopharynx (16.1%). T3-4 disease was present in 68.3%, N2-3 in 37.6%. RT intent was definitive (44.6%), postoperative (49.5%), preoperative (1.6%), or palliative (4.3%). A major change was recommended in 14.5% (18 high-dose PTV, 7 prescription, 1 high-dose PTV and prescription) and implemented in 21 of 26 cases (80.8%). A minor change was recommended in 18.8% (20 low-dose PTV, 10 intermediate-dose PTV, 2 intermediate and low-dose PTV, 2 OAR, and 1 low-dose PTV and OAR) and implemented in 29 of 32 cases (90.6%). Additional workup was suggested in 2 cases (1.1%; 1 imaging study and 1 procedure) and was completed in both cases. Correction of plan changes was associated with a statistically significant delay of 1 day in overall treatment planning (p = 0.001). Discussion A dedicated peer review conference for head and neck RT plans is feasible and well-accepted by providers. Peer review with structured review of head and neck RT contour volumes is associated with substantial rates of suggested and implemented modifications to the plan with minimal treatment delay. Head and neck radiotherapy (RT) is complex, involving multiple targets and organs at risk (OARs). Routine RT plan peer review is often inadequate for thorough review of the head and neck targets and OARs. Patients treated between August 2020 and December 2021 were evaluated in a weekly structured head and neck RT plan peer review conference including at least one head and neck RT subspecialist. Patient and disease factors were recorded, as were the results of the peer review discussion, including the number and nature of recommended RT plan modifications and the rate of implementation. A major change was defined as any modification to the high-dose planning target volume (PTV) or RT prescription or fractionation. A minor change was defined as modification to at least one of the intermediate-dose PTV, low-dose PTV, or any OAR. 186 patients treated by 8 individual providers were prospectively recorded, 86.6% from the main site and 13.4% from 3 regional practices. The most common primary sites were oropharynx (29.6%), oral cavity (22%), cutaneous (16.7%), larynx/hypopharynx (16.1%). T3-4 disease was present in 68.3%, N2-3 in 37.6%. RT intent was definitive (44.6%), postoperative (49.5%), preoperative (1.6%), or palliative (4.3%). A major change was recommended in 14.5% (18 high-dose PTV, 7 prescription, 1 high-dose PTV and prescription) and implemented in 21 of 26 cases (80.8%). A minor change was recommended in 18.8% (20 low-dose PTV, 10 intermediate-dose PTV, 2 intermediate and low-dose PTV, 2 OAR, and 1 low-dose PTV and OAR) and implemented in 29 of 32 cases (90.6%). Additional workup was suggested in 2 cases (1.1%; 1 imaging study and 1 procedure) and was completed in both cases. Correction of plan changes was associated with a statistically significant delay of 1 day in overall treatment planning (p = 0.001). A dedicated peer review conference for head and neck RT plans is feasible and well-accepted by providers. Peer review with structured review of head and neck RT contour volumes is associated with substantial rates of suggested and implemented modifications to the plan with minimal treatment delay.

WE4.7 Is Routine Histopathological Examination Required for all Surgically Resected Gallbladders?

Abstract Aims The aim of this study was to identify both pre- and intra-operative factors in individuals diagnosed with incidental gallbladder malignancy on histopathology following a cholecystectomy for symptomatic gallstone disease. Methods Retrospective records were analysed from October 2018 to December 2020 of all individuals who underwent a cholecystectomy in a single surgical unit. Demographic data (age, gender), presenting complaint, pre-operative imaging (USS/CT/MRCP/ERCP),pre-operative blood results, type of surgery (laparoscopic/open), intra-operative finding (macroscopic appearance of gallbladder) and histopathological findings were noted. Results 829 individuals underwent cholecystectomy for symptomatic gallstone disease within the study period. 73.5% were female. Mean age of patients was 51.2 years. Commonest presenting complaint was pain in all cases followed by nausea (33.5%) and vomiting (26.9%). Chronic cholecystitis was found to be the most common histopathological finding (84.4%), followed by cholelithiasis (31.8%) and cholesterolosis (10.3%.) Gallbladder carcinoma was incidentally found in 3 cases (0.4%), of which 2 were female with a mean age of 75.3 years. A thickened gallbladder was found in all cases on pre-operative imaging and macroscopic abnormalities were noted in all cases intra-operatively with each individual having T2 disease on TNM staging. No individual with normal macroscopic appearance had gallbladder malignancy. Conclusion Pre- and peri-operative findings play a key role in determining incidental findings of gallbladder malignancy and we advocate a more selective approach in the gallbladders that are sent for histopathological examination based on pre-operative imaging, intra-operative macroscopic appearance and age of individual thereby, reducing both cost and the workload of the pathologist.

Tumor stage-specific trends of sentinel lymph node biopsy for vulvar melanoma (406)

<b>Objectives:</b> Vulvar melanoma is a rare and understudied malignancy. Due to its poor prognosis, management has included vulvectomy and complete bilateral inguinofemoral lymphadenectomy. The Standard of care for cutaneous melanomas is to perform sentinel lymph node (SLN) biopsy during excision of intermediate thickness lesions. Lymph node dissection in the inguinofemoral region can result in significant morbidity; thus, the utilization of SLN biopsy for vulvar melanoma is under active investigation. The Standard of care regarding SLN biopsy for vulvar melanoma is not yet determined due to limited prospective data. The objective of this study was to examine the trends and outcomes related to SLN biopsy for vulvar melanoma in the United States according to the local tumor stage. <b>Methods:</b> This population-based retrospective cohort study utilized the National Cancer Institute's Surveillance, Epidemiology, and End Result program from 2004 to 2018. The study population included women with non-metastatic T1-4 stage vulvar melanoma who underwent vulvectomy and had data regarding the method of nodal evaluation. The exposure assignment was based on nodal evaluation: lymphadenectomy, SLN biopsy, or no surgical nodal evaluation. The main outcome was <i>(i)</i> temporal trends of lymphadenectomy or SLN biopsy based on T stage, assessed with a three-year time increment and the Cochrane-Armitage trend test, and <i>(ii)</i> overall survival related to SLN biopsy assessed with inverse probability of treatment weighting propensity score. <b>Results:</b> A total of 729 women with T1-4 vulvar melanoma were examined for analysis. For T1 disease (<i>n</i>=215), the utilization of SLN biopsy significantly increased from 16.7% to 38.9% (<i>p</i>=0.002) over time. For T2 disease (<i>n</i>=156) and T3 disease (<i>n</i>=120), the frequency of SLN biopsy was unchanged during the study period (T2 disease, 22.6% to 26.6%, <i>p</i>=0.279; and T3 disease, 27.3% to 37.0%, <i>p</i>=0.812). For T4 disease (<i>n</i>=238), there was a statistically significant increase in the number of women receiving SLN biopsy from 21.2% to 32.9% (<i>p</i>=0.042) during the study period. Across the four disease groups, the SLN biopsy and LND groups had comparable overall survival in the weighted models (all <i>p</i>>0.05). <b>Conclusions:</b> This large sample size, population-based study found an upward trend in performance of SLN biopsy in both T1 and T4 vulvar melanoma in the past decade in the United States. In T2 and T3 vulvar melanoma, SLN biopsy did not increase. While SLN biopsy is standard in T2-3 cutaneous melanoma, it appears to be less utilized in these tumor stages of vulvar melanoma. Given the significant morbidity associated with inguinal lymph node dissection, further research is warranted on whether these trends have truly resulted in decreased perioperative morbidity.

Results of computer tomography-based adaptive brachytherapy in combination with whole-pelvic- and central-shielding-external beam radiotherapy for cervical cancer

To evaluate treatment results and investigate predictors of local control. In this retrospective study of 236 patients with cervical cancer, we administered CT-based adaptive brachytherapy (BT) in combination with whole- pelvic (WP)- and central shielding (CS)- external beam radiotherapy (EBRT) with or without chemotherapy. The study cohort comprised patients with cervical cancer treated with definitive radiotherapy (RT) or concurrent chemoradiotherapy between June 2013 and March 2019. Local control (LC), overall survival (OS), and late toxicity were evaluated. Predictive factors for LC were analyzed by univariate and multivariate analyses. Median doses of WP- and CS-EBRT and BT were 30.6 GyEQD2, 19.8 GyEQD2, and 40.3 GyEQD2, respectively. The 3-year LC rates for T1b2, T2a, T2b, T3b, and T4 were 100%, 100%, 97.3%, 86.9%, and 91.7%, respectively (p = 0.346). The 3-year OS for Stages IB, IIB, IIIB, IIIC, and IVA were 100%, 94.8%, 82.5%, 81.7%, and 74.6%, respectively (p = 0.037). Rates of Grade 3-4 gastrointestinal and genitourinary toxicities were 3.8% and 1.7%, respectively. Multivariate analysis showed that T3-4, nonsquamous cell histology, and high-risk clinical target volume (CTVHR) D90 of BT < 36GyEQD2 were independently associated with significantly poorer LC. The combination of WP- and CS-EBRT and CT-based IGBT with or without concurrent chemotherapy produced favorable LC outcomes with low rates of late toxicities for patients with small or medium-sized tumors. However, LC was less favorable for patients who had large T3 disease, and the use of CS requires caution in these patients.

Incorporation of sentinel lymph node biopsy in cervical cancer surgery: Recent U.S. population trends (342)

<b>Objectives:</b> The utility of sentinel lymph node (SLN) biopsy in the surgical treatment of women with early cervical cancer is currently under active investigation. This study examined the trends, characteristics, and outcomes of SLN biopsy for cervical cancer surgery. <b>Methods:</b> This retrospective observational study queried the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. The study population included women with invasive cervical cancer (squamous cell carcinoma, adenocarcinoma, and adenosquamous carcinoma) who underwent both hysterectomy and lymphadenectomy for non-metastatic T1 disease from 2003-2018. The exposure allocation was per lymph node evaluation type (SLN biopsy or lymphadenectomy). The main outcome measures were <i>(i)</i> trend of utilization and patient characteristics related to SLN biopsy assessed with multivariable analysis and <i>(ii)</i> overall survival associated with SLN biopsy assessed with propensity score inverse probability of treatment weighting. Sensitivity cohorts included uterine-preserving conservative surgeries. <b>Results:</b> A total of 12,966 women met the inclusion criteria. Of those, 430 (3.3%) women underwent SLN biopsy. The utilization of SLN biopsy increased significantly from 0.8% to 15.2% during the study period (p<0.001). This association remained independent in multivariable analysis: 2011-2014 versus 2003-2010 with an adjusted odds ratio of 4.87, 95% CI: 3.29-7.23, and 2015-2018 versus 2003-2010 with an adjusted odds ratio of 20.6, 95% CI: 14.6-29.2. In a propensity score weighted model, women who had SLN biopsy had similar overall survival compared to those without SLN biopsy (3-year rates, 94.8% vs 94.2%, HR: 0.95, 95% CI: 0.64-1.41, p=0.799). The increase in SLN biopsy was also observed in uterine-preserving surgeries (3.5% to 9.6% for trachelectomy, p=0.043; and 2.5% to 19.5% in cervical excision, p<0.001). <b>Conclusions:</b> The landscape of surgical nodal evaluation is shifting from lymphadenectomy to SLN biopsy in cervical cancer surgery. Survival effects of SLN biopsy-incorporated surgical treatment in early cervical cancer merit further evaluation. Fig. 1

Sequential Intravesical Gemcitabine and Docetaxel for bacillus Calmette-Guérin-Naïve High-Risk Nonmuscle-Invasive Bladder Cancer.

Bacillus Calmette-Guérin (BCG) is currently recommended as adjuvant therapy following complete transurethral resection of bladder tumor for high-risk nonmuscle-invasive bladder cancer (NMIBC). In response to the BCG shortage, gemcitabine plus docetaxel (Gem/Doce) has been utilized at our institution in the BCG-naïve setting. We report the outcomes of patients with high-risk BCG-naïve NMIBC treated with Gem/Doce. We retrospectively reviewed patients with BCG-naïve high-risk NMIBC treated with Gem/Doce from May 2013 through April 2021. Patients received 6 weekly intravesical instillations of sequential 1 gm gemcitabine and 37.5 mg docetaxel after complete transurethral resection of bladder tumor. Monthly maintenance of 2 years was initiated if disease-free at first followup. The primary outcome was recurrence-free survival. Survival was assessed with the Kaplan-Meier method, indexed from the first Gem/Doce instillation. Adverse events were reported using CTCAE (Common Terminology Criteria for Adverse Events) v5 (National Cancer Institute, Bethesda, Maryland). Differences were assessed with the log-rank test. There were 107 patients with a median followup of 15 months included in the analysis. Patients had high-risk characteristics including 47 with any carcinoma in situ and 55 with T1 disease. Recurrence-free survival was 89%, 85% and 82% at 6, 12 and 24 months, respectively. Recurrence rates were similar between patients with or without carcinoma in situ (p=0.42). No patient had disease progression or died of bladder cancer. One patient underwent cystectomy due to end-stage lower urinary tract symptoms. Overall survival was 84% at 24 months. There were 92 adverse events (1 ≥grade 3), and 4 (4%) patients were unable to receive a full induction course. Gem/Doce is an effective and well-tolerated therapy for BCG-naïve NMIBC. Further investigation is warranted.

A Reappraisal of Definitive Chemoradiotherapy for Older Adults With Advanced Head and Neck Cancer.

Definitive treatment for locally advanced head and neck squamous cell carcinoma (LAHNSCC) is often compromised in older adults due to concerns about potential treatment toxicity intolerance. We reviewed our institutional experience with definitive management of older adults with LAHNSCC. From our Institutional Review Board-approved registry, we identified patients aged >60 years with stage III-IV, M0 LAHNSCC (seventh/earlier editions of the American Joint Committee on Cancer classification) treated with definitive radiotherapy from 1993-2019. Indications for concurrent chemotherapy included T3-4 or N2-3 disease. Multivariable analysis using Fine and Gray regression was performed to identify risk factors associated with recurrence. The cumulative incidence method was used to calculate recurrence rates. Overall, 350 patients were identified: 223 aged 60-69, 82 aged 70-74, and 45 aged ≥75 years. Median follow-up was 36.3 months. Two-year recurrence rates were 13.7%, 20.2% and 34.8%, respectively; human papillomavirus-positive disease was present in 190 (85%), 44 (54%), and 25 (56%), respectively; and systemic therapy was given to 194 (87%), 64 (88%), and 23 (56%) patients, respectively. Factors significantly associated with increased risk of recurrence included age ≥75 years, Karnofsky performance status 70-80, clinical N2c-N3, and Charlson score 2-3. Patients aged ≥75 years received less aggressive therapy and experienced increased recurrence compared to younger patients. Outcomes for those aged 70-74 years were similar to younger patients treated with aggressive therapy, despite their inferior performance status/comorbidity, and such patients should not routinely be excluded from standard-of-care therapy. Further study is needed to optimize therapy for a redefined older adult (age ≥75 years) population.

Outcomes and Toxicities of Nonmedullary Thyroid Tumors Treated with Proton Beam Radiation Therapy.

PurposeProton therapy is an emerging therapy for several malignancies owing to its favorable therapeutic ratio. There are very limited data on the use of proton therapy in the management of thyroid carcinoma. Our objective was to review the safety, feasibility, and outcomes of proton therapy for patients with thyroid cancer treated to the head and neck.MethodsFrom our institution's proton database from 2012 to 2021, we identified 22 patients with thyroid cancer treated with proton beam therapy. We evaluated outcomes and toxicities.ResultsMedian follow-up was 26 months. Of the 22 patients, 50% were female. The mean age was 65 years. Three patients had anaplastic cancer; 13, papillary carcinoma; 2, follicular carcinoma; and 2, poorly differentiated carcinoma. Forty-six percent had T4 disease. Primary targets were the central neck compartment, level VI, and upper mediastinum. Radiation dose was 60 GyRBE adjuvantly, and 70 GyRBE for gross disease (range, 6000-7600 GyRBE). Eight patients underwent upfront adjuvant radiation, and 3 received definitive radiation for unresectable disease upfront. Eleven patients received either salvage or palliative radiation. Fifty-nine percent of patients had extrathyroidal extension, and 64% of patients had gross disease in the neck before treatment. Fifty percent of patients had metastatic disease before treatment. Sixteen patients received concurrent chemotherapy, 63% of these patients received doxorubicin. For all patients, 1-year local regional recurrence (LRR) was 0%, and overall survival (OS) was 90%. Acute grade 3+ toxicities occurred in 27% of patients, the most frequent being dermatitis (27%). Three patients required a percutaneous endoscopic gastrostomy tube after radiation therapy (RT), 2 owing to progression. There were no grade 4+ toxicities.ConclusionsProton therapy for thyroid cancer appears feasible and effective with minimal toxicities. Prospective studies comparing proton therapy with intensity-modulated RT, to evaluate the clinical efficacy of using proton therapy to reduce toxicities in patients undergoing radiation for thyroid cancer, are warranted.

Impact of Insurer on Papillary Thyroid Carcinoma Outcomes, Stage, and Treatment Modalities.

While the impact of insurance has been described for thyroid cancer as a whole, we sought to further characterize this relationship for the papillary sub-group (PTC). Those patients with primary site thyroid tumors from 2007 to 2016 with histology-confirmed PTC were extracted from the SEER database. These parameters yielded 103 219 participants for demographic, extent of disease, and treatment parameter study and 103 025 for outcome studies. Compared to their counterparts, those with Medicaid were more likely to have stage T3 or greater (<.0001) disease at presentation. Those with Medicare/private insurance were more likely to have No staging at diagnosis (P < .0001). Similarly, those with Medicaid exhibited poorer overall (98.0%, 90.9%, 81.6% vs 98.9%, 95.0%, 90.0%; P < .0001) and cause-specific (99.3%, 98.0%, 95.8% vs 99.7%, 99.1%, 98.4%; P < .0001) survival after 1, 5, and 9 years respectively. Insurer has a significant impact on the stage at diagnosis of papillary thyroid carcinoma while having limited effect on the treatment modalities offered. Statistically significant overall and cause-specific mortality differences were appreciated but are likely clinical insignificant. Further work to elucidate the social factors likely affecting these patients is warranted.

Proton Therapy Outcomes for Head and Neck Cutaneous Melanoma: Proton Collaborative Group Analysis.

PurposeReports of proton beam therapy (PBT) utilization for cutaneous melanoma of the head and neck (HN) region is virtually non-existent. This study reports on the efficacy and acute toxicities of PBT for primary HN cutaneous melanoma.Materials and MethodsWe queried the prospectively collected, multi-institutional Proton Collaborative Group registry for all consecutive patients with HN cutaneous melanoma receiving PBT from May 2010 to December 2019. Kaplan-Meier methods were used to estimate overall survival (OS), progression free survival (PFS), and local regional recurrence free survival (LRFS). Toxicity was reported per CTCAE version 4.0.ResultsA total of 8 patients were identified with a median age of 69 (range, 37-88). All patients (100%) underwent surgery followed with postoperative PBT. There were 3 patients (37.5%) with T3 or T4 disease and 4 (50%) with N2 or N3 disease. The median radiation dose was 46 GyRBE (range, 27-70) and median dose per fraction was 2.4 GyRBE (range, 2.0-6.0) with the most common dose fractionation being 44 or 48 GyRBE in 20 fractions (n = 4). At a median follow-up of 40.1 months (range, 1.6-62.4) the 1 and 3 year OS rates were 85.7% and 35.7%, respectively. The median PFS was 25.40 months (95% CI, 2.53-58.70) while PFS at 1 year and 3 years was 85.7% and 35.7%, respectively. LRFS was 100% at 1 year and 85.7% at 3 years. Five of the 8 patients developed distant metastases, of which 3 received immunotherapy. Acute G2+ and G3+ toxicities occurred in 5 of 8 patients and 2 of 8 patients, respectively. G3 toxicities included radiation dermatitis (n = 1) and immunotherapy-related rash (n = 1). No G4+ toxicities were reported.ConclusionSingle modality PBT for HN melanomas in the definitive setting provides effective and durable local control rates with tolerable acute toxicity. Distant failure remains the primary pattern of failure.

Intraoperative radiation therapy for early-stage breast cancer: a single-institution experience.

BackgroundTo assess outcomes and toxicity after low-energy intraoperative radiotherapy (IORT) for early-stage breast cancer (ESBC).Materials and methodsWe reviewed patients with unilateral ESBC treated with breast-conserving surgery and 50-kV IORT at our institution. Patients were prescribed 20 Gy to the surface of the spherical applicator, fitted to the surgical cavity during surgery. Patients who did not meet institutional guidelines for IORT alone on final pathology were recommended adjuvant treatment, including additional surgery and/or external-beam radiation therapy (EBRT). We analyzed ipsilateral breast tumor recurrence, overall survival, recurrence-free survival and toxicity.ResultsAmong 201 patients (median follow-up, 5.1 years; median age, 67 years), 88% were Her2 negative and ER positive and/or PR positive, 98% had invasive ductal carcinoma, 87% had grade 1 or 2, and 95% had clinical T1 disease. Most had pathological stage T1 (93%) N0 (95%) disease. Mean IORT applicator dose at 1-cm depth was 6.3 Gy. Post-IORT treatment included additional surgery, 10%; EBRT, 11%; adjuvant chemotherapy, 9%; and adjuvant hormonal therapy, 74%. Median total EBRT dose was 42.4 (range, 40.05–63) Gy and median dose per fraction was 2.65 Gy. At 5 years, the cumulative incidence of ipsilateral breast tumor recurrence was 2.7%, the overall survival rate was 95% with no breast cancer-related deaths, and the recurrence-free survival rate was 96%. For patients who were deemed unsuitable for postoperative IORT alone and did not receive recommended risk-adapted EBRT, the IBTR rate was 4.7% versus 1.7% (p = 0.23) for patients who were either suitable for IORT alone or unsuitable and received adjuvant EBRT. Cosmetic toxicity data was available for 83%, with 7% experiencing grade 3 breast toxicity and no grade 4–5 toxicity.ConclusionsIORT for select patients with ESBC results in acceptable outcomes in regard to ipsilateral breast tumor recurrence and toxicity.

Impact of COVID-19 pandemic on breast cancer care: report from a regional cancer centre

BackgroundThe COVID-19 pandemic has deeply disrupted cancer care, both during and after lockdowns. In this study, we analysed the treatment delay in patients with breast cancer due to COVID-19 pandemic in India.MethodsFrom March 2, 2020, to March 31, 2021, patients with breast cancer who presented to the breast clinic in the department of Radiotherapy & Oncology, Regional Cancer Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India were included in this analysis. Delays to the start of chemotherapy, surgery, and radiotherapy faced by patients with breast cancer were recorded. Delays to the patient treatment due to the COVID-19 pandemic were calculated and its impact on disease outcomes was analysed.Findings405 women were registered in the breast clinic. Diagnosis was delayed for up to 3 months for 144 (36%) patients, 4–6 months for 70 (17%) patients, 7–9 months for 43 (11%) patients, 10–11 months for 37 (9%) patients, and 12 or more months for 111 (27%) patients. Localised disease at presentation was observed in 360 (89%) patients, and metastatic disease in 45 (11%) patients. A total of 161 (40%) patients had delays to their treatment: chemotherapy was delayed for 45 (11%) patients, surgery for 56 (14%) patients, and radiotherapy for 90 (22%) patients. 19 (5%) patients were lost to follow-up. Disease progression occurred in 33 (20%) of 161 patients who had delays to start of treatment. Significantly more patients (64 [40%] of 161) who faced delays to treatment presented with T4 disease than patients who did not face delays (58 [26%] of 225; p=0·010). A significantly greater number of patients required neoadjuvant chemotherapy because of the delay at the start of treatment (90 [56%] vs 59 (26%) patients who did not face delays; p<0·0001). 142 (88%) of 161 patients who faced treatment delays and in 193 (86%) of 225 patients who did not face delays underwent surgery (either lumpectomy or mastectomy). More patients who faced treatment delays (107 [75%] of 142) had to undergo mastectomy than did patients who did not face delays (131 [68%] of 193). In patients with disease progression, median delay to start of chemotherapy was 3 months (IQR 2–8), median delay to start of surgery was 3 months (2–6), and median delay to start of radiotherapy was 2 months (2–4).InterpretationDue to delays in diagnosis and start of treatment, more patients presented with advanced tumours, which resulted in a greater number of patients needing neoadjuvant chemotherapy. Presentation in advanced stage translated to more mastectomies in these patients. Smaller delays to the start of radiotherapy could be because radiotherapy facilities were still operational during the COVID-19 pandemic. Delays to the start of treatment of breast cancer led to disease progression in one-fifth of affected patients, which can negatively affect their survival. Patients affected by delays to diagnosis or start of treatment need to be followed-up on for monitoring of effects of these delays on survival.FundingNone.

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