Short-course Radiotherapy Research Articles

Healthcare Cost Analysis of Short-Course vs. Long-Course Pre-Operative Radiotherapy Schedules for Rectal Cancer

Purpose/Objective(s)One aspect of alternate radiotherapy (RT) techniques for rectal cancer not well studied in the United States is cost. Herein, we report a financial analysis to assess cost savings associated with short course (SC) versus long course (LC) RT and determine which parties (payor, patient, or both) benefit from the aforementioned savings.Materials/MethodsA focused analysis on neoadjuvant RT for operable rectal cancer was designed to study four regimens: (1) SC utilizing three-dimensional conformal RT (3DCRT) [SC-3D], (2) SC utilizing intensity-modulated RT (IMRT) [SC-IMRT], (3) LC utilizing 3DCRT [LC-3D], and (4) LCRT utilizing IMRT [LC-IMRT]. Variable and fixed patient costs were reported. Patient and payor costs based on regimen were summated to determine societal costs. A sensitivity analysis based on 40 rectal cancer patients per year using SC and LC RT was performed.ResultsTechnical costs account for most of the disparity between payor costs when selecting between IMRT and 3D ($2,472.25-7,623.13), while professional costs remain somewhat stable ($651.25-1,645.58). LCRT-related patient costs ($1,382.94) were found to be higher than SCRT patient costs ($353.22) as patients undergoing LCRT had a greater number of treatment days. This disparity persists when evaluating total societal cost, as the costliest regimen, LC-IMRT ($20,810.77), is almost twice the next expensive regimen, LC-3D ($11,503.00).ConclusionSocietal burden varies significantly with technique and length of treatment for pre-operative rectal cancer RT. Anticipated changes in health policy and reimbursement patterns are likely to disincentivize routine LC and IMRT use in rectal cancer. Further study into patient-centric and resource-conscious medical decision making is warranted. One aspect of alternate radiotherapy (RT) techniques for rectal cancer not well studied in the United States is cost. Herein, we report a financial analysis to assess cost savings associated with short course (SC) versus long course (LC) RT and determine which parties (payor, patient, or both) benefit from the aforementioned savings. A focused analysis on neoadjuvant RT for operable rectal cancer was designed to study four regimens: (1) SC utilizing three-dimensional conformal RT (3DCRT) [SC-3D], (2) SC utilizing intensity-modulated RT (IMRT) [SC-IMRT], (3) LC utilizing 3DCRT [LC-3D], and (4) LCRT utilizing IMRT [LC-IMRT]. Variable and fixed patient costs were reported. Patient and payor costs based on regimen were summated to determine societal costs. A sensitivity analysis based on 40 rectal cancer patients per year using SC and LC RT was performed. Technical costs account for most of the disparity between payor costs when selecting between IMRT and 3D ($2,472.25-7,623.13), while professional costs remain somewhat stable ($651.25-1,645.58). LCRT-related patient costs ($1,382.94) were found to be higher than SCRT patient costs ($353.22) as patients undergoing LCRT had a greater number of treatment days. This disparity persists when evaluating total societal cost, as the costliest regimen, LC-IMRT ($20,810.77), is almost twice the next expensive regimen, LC-3D ($11,503.00). Societal burden varies significantly with technique and length of treatment for pre-operative rectal cancer RT. Anticipated changes in health policy and reimbursement patterns are likely to disincentivize routine LC and IMRT use in rectal cancer. Further study into patient-centric and resource-conscious medical decision making is warranted.

Feasibility of Organ Preservation With Short Course Radiation Therapy as Part of Total Neoadjuvant Therapy in Locally Advanced Rectal Cancer During the COVID-19 Pandemic

Purpose/Objective(s)While long course chemoradiation therapy has been studied as part of a watch-and-wait (WW) strategy for patients with locally advanced rectal cancer, it is unclear whether short-course radiation therapy (SCRT) will be associated with similar rates of organ preservation. We hypothesized that a WW strategy to facilitate organ preservation with SCRT, as part of a total neoadjuvant therapy (TNT) approach during the COVID-19 pandemic, would be both safe and feasible.Materials/MethodsFrom March to June of 2020, due to the COVID-19 pandemic, per institutional policy, all patients undergoing radiation therapy for locally advanced rectal cancer were treated with SCRT. After completion of SCRT-TNT, patients were clinically restaged by exam, endoscopy and MRI and the decision was made to manage the patient surgically or with a WW approach. The decision for WW or surgery was made by the surgeon in conjunction with patient consent. After IRB waiver was obtained, we reviewed consecutive patients treated during our SCRT mandate. The main outcome of interest was total mesorectal excision (TME)-free survival among patients eligible for WW after SCRT-TNT.ResultsOur cohort included 42 patients with a median age of 57 years (Interquartile Range [IQR] 48-67), 24 (57%) of whom were male. Median follow-up from end of SCRT-TNT was 7 months (IQR 6-8). The median tumor cranio-caudal size was 4.1 cm (IQR 3.3-5.2) with a median distance from the anal verge of 7 cm (IQR 5-9). The majority had cT3 (71%) or cN+ (74%) disease. Patients underwent a median of 14 weeks (IQR 13-15) of FOLFOX or CAPEOX chemotherapy, with 32 (76%) patients receiving chemotherapy prior to SCRT and 10 (24%) patients receiving chemotherapy after SCRT. The median time from completion of TNT to endoscopic restaging was 9 weeks (IQR 7-10). Nineteen (45%) patients were recommended to undergo surgical resection, of whom 17 went on to TME and 2 refused TME. Of the 15 patients with pathology available, 2 had a pCR (13%). Notably, one of these patients had a cCR at post-TNT endoscopy, but due to the presence of a stricture, WW was deemed unfeasible. Of the 23 patients managed by a WW strategy after SCRT-TNT completion, 19 had a clinical complete response (cCR), 3 had a near-CR, and 1 had an incomplete response. The 6-month TME-free survival was 85% for patients on WW. Four (17%) patients had a local regrowth at a median of 20 weeks (IQR 17-24), 3 of whom were salvaged with TME and 1 who declined surgery and opted for further surveillance. One of these patients had regrowth confirmed by biopsy, but had a pCR confirmed in the TME specimen. The 6-month TME- free survival of the entire cohort was 52%, and the combined pCR/6-month cCR was 52%.ConclusionOur data suggest WW after SCRT-TNT is feasible. Longer term follow-up is required to confirm the durability and oncologic safety of these results.

Analysis of Pathologic Complete Response Rates Between Different Neoadjuvant Radiation Treatment Regimens for Rectal Cancer

The standard of care for rectal cancer is either long or short course radiation followed by surgery with or without adjuvant chemotherapy. Recently, total neoadjuvant therapy, an approach consisting of giving all chemotherapy and radiotherapy prior to definitive surgery, has been a promising alternative. This study aims to assess the pathologic complete response (pCR) rates among different neoadjuvant treatment regimens and determine if neoadjuvant chemotherapy improves pCR rates.Electronic medical databases were queried to identify rectal cancer patients treated with neoadjuvant therapy at our institution from 2006-2019. Patients were grouped according to neoadjuvant therapy received: long-course chemoradiation (CRT), long-course chemoradiation with chemotherapy (CRT TNT), short-course radiation (SCRT), and short-course radiation with chemotherapy (SCRT TNT). Patients without follow-up data or surgical pathology reports were excluded. pCR was defined as no evidence of disease at surgery. pCR rates were determined and compared using Chi-square analysis.A total of 249 patients were analyzed. Table 1 shows treatment characteristics in each group. There were 200 (80.3%) patients who received CRT, 26 (10.4%) who received CRT TNT, 13 (5.2%) who received SCRT, and 10 (4%) who received SCRT TNT. Initial stage was different between groups, with metastatic patients more likely to receive SCRT TNT (P < 0.001). The median time to surgery were significantly different between groups (P < 0.001). Eleven (42.3%) and 6 (60%) patients received FOLFOX, and 13 (50%) and 4 (40%) of the patients received XELOX for CRT TNT and SCRT TNT, respectively. The remaining patients (7.7%) in the CRT TNT group received Capecitabine. For CRT, 53 (26.5%) patients achieved pCR, 3 (11.5%) in CRT TNT, 1 (7.7%) in SCRT, and 2 (20%) in SCRT TNT. None of these differences were statistically different (P = 0.19). On univariate analysis, age (P = 0.13), clinical T stage (P = 0.13), clinical N stage (P = 0.95), time to surgery (P = 0.82), and presence of chemotherapy in the neoadjuvant regimen (P = 0.22) were not significant predictors for pCR.Total neoadjuvant treatment for rectal cancer did not improve pCR rates over standard chemoradiation or short course radiation alone, which is contrary to what published series suggest. These results maybe be explained in part by the fact that chemotherapy was delivered first and the time from completing radiation to the time of surgery was not significantly different between groups. These data suggest that meaningful gains in pCR rates may be achieve by sequencing chemoradiation earlier in the TNT course. Future studies are needed to investigate this hypothesis.

Dosimetry Evaluation of Locally Advanced Rectal Adenocarcinoma Treated With Short-Course Radiotherapy and Sequential Multi-Agent Chemotherapy With Non-Operative Intent

Short course radiotherapy (SCRT) followed by chemotherapy (CH) with non-operative intent is a promising treatment option for rectal adenocarcinoma. We evaluated the incidence, severity, and dosimetric predictors of acute and late toxicities for patients treated with SCRT-CH undergoing non-operative management.From January 2018 to May 2019, 90 patients with newly diagnosed, non-metastatic rectal adenocarcinoma were treated with SCRT-CH. 42 patients with cCR have not required surgical intervention to date and were included in this analysis. Patients received 25 Gy /5 fx to the pelvis with an optional primary boost to 30 Gy. Patients were evaluated every 3 months for recurrence and toxicity. Treatment plans were assessed for mean dose, max dose, V125%, V105%, V100%, V80% for the following structures: PTV, anal canal, rectum, large bowel, small bowel, and entire bowel. Toxicities were graded per CTCAEv5.0. Patients with clinically significant toxicity were compared to those without by the Mann-Whitney U test. The difference was statistically significant at the p < 0.05 level.Of the 42 patients evaluated, the average age was 61.9 years (range 24-85) and 23 (54.8%) were male. Four patients (9.5%) developed grade 3 acute gastrointestinal toxicities. The grade 3 toxicities of colitis, diarrhea, and ileus occurred during CH. One grade 3 rectal pain occurred shortly after completion of SCRT. Dosimetric parameters are reported in Table 1 below; there were no statistically significant differences (P > 0.05) in the evaluated dosimetric variables between patients with and without clinically significant toxicity. No late grade 3 or greater GI toxicities were present at last follow-up.In this dosimetric evaluation of SCRT-CH and non-operative management for rectal adenocarcinoma no dosimetric variables were associated with grade 3 or greater toxicities. These data can provide the foundation for future studies, including evaluating dose escalation, in SCRT-CH non-operative treatment.

Multi-Institutional Comparison of SC-TNT and LC-TNT for Rectal Cancer Non-Operative Management

Recent data support the use of total neoadjuvant therapy (TNT) for treatment of locally advanced rectal cancer (LARC), although the optimal TNT regimen and therapy sequence is unclear for non-operative management (NOM). We performed a multi-institutional comparison of short-course radiation (SCRT) followed by consolidation chemotherapy (SC-TNT) versus long-course chemoradiation (CRT) preceded by induction chemotherapy (LC-TNT), after adoption of NOM at both institutions.The records of 187 patients with cT2-4N0-2 rectal cancer treated between 2016-2020 with TNT at two academic institutions were reviewed under an IRB-approved protocol. The SC-TNT cohort (institution 1) included 85 patients treated with SCRT (25-30 Gy in 5 fx) followed by FOLFOX/CAPOX (n = 82) or capecitabine (n = 3). The LC-TNT cohort (institution 2) included 102 patients treated with FOLFOX/CAPOX followed by CRT (45-56 Gy at 1.8-2 Gy/fx) with concurrent fluoropyrimidine-based chemotherapy. Patients with a clinical complete response (cCR) were offered NOM. The rates of cCR were compared between SC- and LC-TNT. Disease-free survival (DFS) was compared using the log-rank test. To account for any differences in NOM selection between institutions, local-only tumor regrowth was censored from DFS if salvaged with R0 resection, and the overall complete response (CR) rate, defined as cCR + pCR rate for patients undergoing surgery, was assessed. Multivariate analysis (MVA) was performed with logistic and Cox regression to determine factors associated with CR and DFS, respectively.The median age at diagnosis was 60 and 54 years for SC-TNT and LC-TNT cohorts, respectively (P = 0.002). All other characteristics including performance status, tumor location, and clinical stage were balanced. The median duration of neoadjuvant FOLFOX/CAPOX chemotherapy was 105 vs 98 days for the SC-TNT and LC-TNT cohorts, respectively (P = 0.001). The median follow-up was 27 months. The cCR rate was higher in the SC-TNT cohort (44/85, 52.8% vs 21/102, 20.6%, P < 0.001), with a trend for improved CR rate for SC-TNT (54.1% vs 40.2%, P = 0.057). On MVA, use of SC-TNT was associated with improved CR (HR = 2.24, 95% CI: 1.13-4.45, P = 0.021). Among patients undergoing NOM, 33/39 patients (84.6%) in the SC-TNT group and 10/17 patients (58.8%) in the LC-TNT group (P = 0.27) were free from local recurrence at 1 year. Two-year DFS was 93.4% and 95.4% for the SC-TNT and LC-TNT cohorts with improved DFS on log-rank test for LC-TNT (P = 0.023), but no DFS difference on MVA between SC-TNT and LC-TNT (HR = 2.29, 95% CI: 0.8-6.51, P = 0.121).SC-TNT demonstrated a greater rate of cCR compared to LC-TNT, without DFS difference on MVA. Although future studies are warranted to compare SC-TNT with a CRT and consolidative chemotherapy TNT approach, our data support SC-TNT as a suitable regimen for LARC NOM.

Oligometastatic Rectal Adenocarcinoma Treated With Short-Course Radiotherapy and Chemotherapy with Non-Operative Intent of the Primary for Pelvic Complete Responders

Sequential short-course radiotherapy and chemotherapy (SCRT-CH) is a promising treatment for non-operative management of rectal adenocarcinoma. This paradigm has not been evaluated for newly diagnosed oligometastatic (OM1) patients (pts). We evaluated rates of locoregional clinical complete response (cCR), rectal surgeries, and local control (LC) in newly diagnosed OM1 pts treated with definitive treatment of the primary tumor with SCRT-CH with non-operative intent for pts with locoregional cCR.From 2/2018 to 5/2020, 39 pts with newly diagnosed OM1 rectal cancer were treated with SCRT-CH and non-operative intent for locoregional cCR at a single institution. OM1 disease was considered disease confined to ≤ 2 distant sites. Pts received 25 Gy/5 fx to the pelvis with an optional boost to 35 Gy for involved extra-mesorectal lymph nodes. CH was delivered prior to and/or after RT. Locoregional cCR was assessed via DRE, sigmoidoscopy, and/or pelvic MRI following completion of SCRT-CH. Follow-up was calculated from RT completion. Survival was evaluated by Kaplan-Meier method and log rank test.All 39 pts with 47 distant sites completed SCRT and 36 (92%) had CH. 22 (56%) received all CH following RT, and 24 (62%) received at least 2 months of CH after RT. 33 pts received 1st line FOLFOX +/- bevacizumab (bev). 13 pts underwent low anterior resection and 2 pts underwent abdominoperineal resection. 19 pts had 23 distant sites treated. The most common distant site treated was liver and the most common modality was resection. Following SCRT, only 4 pts (10%) experienced a local failure (median 6.4 months, range 0.7-10.7 months). 6/39 experienced a pelvic cCR (15%); all cCR pts received SCRT first followed by at least 2 months of CH. Pts with a cCR were more likely to have received at least 2 months of CH following SCRT compared to patients without a cCR (100% vs. 59%, P < .05). The median follow-up for living pts was 16 months. The 1-year overall survival (OS) was 66% (95% CI: 51-84%) for all pts. Pts who received at least 2 months of CH following SCRT had an improved OS (1-year OS [95% CI]: 82% [68-100%] vs. 29% [10-84%], P < .001 by log-rank) compared to pts who did not.SCRT-CH with non-operative intent for pts in locoregional cCR is a promising treatment paradigm for OM1 rectal cancer pts.

The Evolving Landscape of Treatment Paradigms for Locally Advanced Rectal Cancer: A Survey Study of Gastrointestinal Radiation Oncology Experts

To assess current practice patterns in the treatment of locally advanced rectal cancer among radiation oncologists specializing in gastrointestinal (GI) malignancies.Radiation oncologists specialized in GI malignancies at an ACGME affiliated institution were invited to complete an online survey and select management recommendations for seven locally advanced rectal cancer clinical vignettes, consisting of variable T and N staging, tumor location and high-risk features (presence of enlarged lateral lymph nodes, mesorectal fascia involvement and extramural vascular invasion). Answer choices representing the diversity of current treatment paradigms for rectal cancer included variable sequences of chemotherapy (CHT), radiation (long-course chemoradiation [LC-CRT] or short-course radiation [SCRT]), surgery or non-operative management (NOM). Participation was voluntary and all responses remained anonymous. The survey was open from January to February 2021.Of 207 GI experts invited to participate, 36 replied, resulting in a response rate of 17.4% (36/207). For low rectal tumors (cT3N2) without threatened margins, 80.6% (29/36) recommended total neoadjuvant therapy (TNT) of which 41.4% (12/29) preferred NOM if a clinical complete response was achieved upon restaging. Of those who chose TNT and surgery (17/29), 76.5% preferred LC-CRT (consolidation CHT [53.8%] vs. induction CHT [46.2%]) and 23.5% preferred SCRT. For mid to upper rectal tumors (cT3N1-2) without threatened margins, 66.6% (24/36) recommended TNT and surgery with 38.9% (14/36) electing for SCRT then consolidation CHT, and 22.2% (8/36) for induction CHT then LC-CRT. After TNT, neoadjuvant LC-CRT (16.7%, 6/36) or neoadjuvant SCRT (11.1%, 4/36) followed by surgery and adjuvant CHT were most favored. In patients with mid to upper rectal tumors and threatened margins, SCRT with consolidation CHT and surgery remained the most accepted treatment paradigm (44.4%, 16/36). LC-CRT followed by consolidation CHT was the preferred choice to maximize likelihood of NOM. For a clinical node negative upper rectal tumor (cT3N0), 38.9% (14/36) recommended SCRT, then surgery with adjuvant CHT, 19.4% (7/36) recommended induction CHT then surgery, and 16.7% (6/36) recommended LC-CRT, then surgery with adjuvant CHT.Total neoadjuvant therapy has been widely adopted in the management of locally advanced rectal cancer. For mid to upper rectal tumors, most GI experts recommended SCRT, consolidation CHT and surgery. For low rectal tumors, LC-CRT was preferred with significant variability between consolidation versus induction CHT. As compared to mid and upper rectal tumors, clinicians were more likely to recommend NOM following a clinical complete response for low rectal tumors.

Comparison of Two Palliative Hypofractionated Radiotherapy Regimens in Poor-Prognosis High-Grade Glioma: A Propensity-Matched Analysis

The prognosis of high-grade glioma (HGG) in elderly patients (> 65 years) and/or those with low Karnofsky performance status (KPS ≤60) is generally poor with an expected median survival of 6-10 months despite aggressive multi-modality treatment. The most optimal therapeutic regimen including radiotherapy (RT) dose-fractionation for this group remains an area of active research. In the last two decades, hypofractionated RT using high-dose per fraction (> 2.5-5 Gy/fraction) has been tested as a resource-sparing alternative to conventionally fractionated RT with significant reduction in the number of fractions to limit patient visits and/or shorten overall duration of treatment while achieving similar disease-related outcomes. The present study aimed to assess compliance to planned RT and overall survival (OS) in patients treated with two hypofractionation regimens.Patients with poor-prognosis HGG (elderly and/or poor performance status) receiving post-operative palliative-intent hypofractionated RT following maximal safe resection were included. Hypofractionation comprised of long-course (LC) RT delivering 35 Gy/7 fractions, 5 Gy/fraction, once-weekly over 6-weeks (N = 100) or short-course (SC) RT delivering 35 Gy/10 fractions, 3.5 Gy/fraction, 5 fractions per week over 2-weeks (N = 55). None of the patients were treated with concurrent temozolomide (TMZ) but received adjuvant TMZ 1-month after completion of RT on physician discretion. Age, KPS, and histological grade were used as covariates for propensity-matched analysis to compare LCRT versus SCRT cohorts using OS as the primary endpoint.Baseline patient characteristics were reasonably balanced in the two cohorts. Patients treated with LCRT were somewhat older compared to SCRT (median age 60 vs 56 years) while baseline performance status of LCRT cohort was slightly better than SCRT (median KPS 60 vs 50). The distribution of histologic grade III and IV gliomas was also similar in both cohorts. Compliance to planned RT was significantly better in SCRT compared to LCRT cohort (89% vs 53%, P = 0.03). Propensity-matched analysis included 70 and 53 patients from LCRT and SCRT cohorts respectively. Patients treated with SCRT had significantly better outcomes with median OS of 9.2 months (95% CI: 7.5-10.9 months) compared 3.4 months (95% CI: 2.4-4.6 months) in the LCRT cohort (P = 0.004).SCRT appears to be an optimal resource-sparing palliative hypofractionated RT regimen in patients with poor-prognosis HGG with better compliance to planned therapy and improved survival outcomes.T. Gupta: None. S. Pant: None. B. Likonda: None. A. Dasgupta: None. A. Chatterjee: None. S. Kannan: None. G. Sastri: None. S.R. Trivedi: None. D. Dutta: None. R. Jalali: None.

A randomized phase III study of short-course radiotherapy combined with Temozolomide in elderly patients with newly diagnosed glioblastoma; Japan clinical oncology group study JCOG1910 (AgedGlio-PIII)

BackgroundThe current standard treatment for elderly patients with newly diagnosed glioblastoma is surgery followed by short-course radiotherapy with temozolomide. In recent studies, 40 Gy in 15 fractions vs. 60 Gy in 30 fractions, 34 Gy in 10 fractions vs. 60 Gy in 30 fractions, and 40 Gy in 15 fractions vs. 25 Gy in 5 fractions have been reported as non-inferior. The addition of temozolomide increased the survival benefit of radiotherapy with 40 Gy in 15 fractions. However, the optimal regimen for radiotherapy plus concomitant temozolomide remains unresolved.MethodsThis multi-institutional randomized phase III trial was commenced to confirm the non-inferiority of radiotherapy comprising 25 Gy in 5 fractions with concomitant (150 mg/m2/day, 5 days) and adjuvant temozolomide over 40 Gy in 15 fractions with concomitant (75 mg/m2/day, every day from first to last day of radiation) and adjuvant temozolomide in terms of overall survival (OS) in elderly patients with newly diagnosed glioblastoma. A total of 270 patients will be accrued from 51 Japanese institutions in 4 years and follow-up will last 2 years. Patients 71 years of age or older, or 71–75 years old with resection of less than 90% of the contrast-enhanced region, will be registered and randomly assigned to each group with 1:1 allocation. The primary endpoint is OS, and the secondary endpoints are progression-free survival, frequency of adverse events, proportion of Karnofsky performance status preservation, and proportion of health-related quality of life preservation. The Japan Clinical Oncology Group Protocol Review Committee approved this study protocol in April 2020. Ethics approval was granted by the National Cancer Center Hospital Certified Review Board. Patient enrollment began in August 2020.DiscussionIf the primary endpoint is met, short-course radiotherapy comprising 25 Gy in 5 fractions with concomitant and adjuvant temozolomide will be a standard of care for elderly patients with newly diagnosed glioblastoma.Trial registrationRegistry number: jRCTs031200099.Date of Registration: 27/Aug/2020. Date of First Participant Enrollment: 4/Sep/2020.

Preoperative radiotherapy 5 × 5 Gy and short versus long interval between surgery for resectable rectal cancer: 10-Year follow-up of the randomised controlled trial

BackgroundStudies on short-course preoperative radiotherapy in combination with total mesorectal excision for rectal cancer reported improved local control without clear survival benefits. The optimal fractionation and interval between radiotherapy and surgery are still under debate. We, therefore, aimed to report 10-year results of a randomized clinical trial (RCT, NCT01444495) comparing different time intervals between irradiation and surgery for rectal cancer. Material and methodsData from the RCT conducted at a single academic centre were reviewed based on regular control visits with the median follow-up of 12 years. Patients with rectal cancer were randomly assigned to short-course preoperative radiotherapy (5 × 5 Gy) followed by surgery 7–10 days (short interval) or 4–5 weeks (long interval) after the end of irradiation. The primary endpoint was the local recurrence rate at 5 years. The secondary endpoints included overall survival, disease-free survival, systemic recurrence rate, and downstaging. ResultsA total of 154 patients were randomly assigned to short (n = 77) or long interval (n = 77) surgery. The cumulative incidence of local recurrence at 10 years was 1.3% and 11.7% in the short and long-interval groups, respectively (p = 0.031). Accordingly, the incidence of systemic relapse was 14.3% versus 9.1% (p = 0.0319). There were no differences in the overall 10-year survival between patients subject to short and long-interval surgery (58% vs 61%, p = 0.754). However, patients with downstaging after radiotherapy had significantly better 10-year survival rates than non-responders. ConclusionsShort-course preoperative radiotherapy with delayed surgery demonstrated an increased risk of local relapse over a 10-year follow-up.

Clinical Complete Response in Patients With Rectal Adenocarcinoma Treated With Short-Course Radiation Therapy and Nonoperative Management

This study aimed to determine the clinical efficacy and safety of nonoperative management (NOM) for patients with rectal cancer with a clinical complete response (cCR) after short-course radiation therapy and consolidation chemotherapy. Patients with stage I-III rectal adenocarcinoma underwent short-course radiation therapy followed by consolidation chemotherapy between January 2018 and May 2019 (n = 90). Clinical response was assessed by digital rectal examination, pelvic magnetic resonance imaging, and endoscopy. Of the patients with an evaluable initial response, those with a cCR (n = 43) underwent NOM, and those with a non-cCR (n = 43) underwent surgery. The clinical endpoints included local regrowth-free survival, regional control, distant metastasis-free survival, disease-free survival, and overall survival. Compared with patients with an initial cCR, patients with initial non-cCR had more advanced T and N stage (P = .05), larger primary tumors (P = .002), and more circumferential resection margin involvement on diagnostic magnetic resonance imaging (P < .001). With a median follow-up of 30.1 months, the persistent cCR rate was 79% (30 of 38 patients) in the NOM cohort. The 2-year local regrowth-free survival was 81% (95% confidence interval [CI], 70%-94%) in the initial cCR group, and all patients with local regrowth were successfully salvaged. Compared with those with a non-cCR, patients with a cCR had improved 2-year regional control (98% [95% CI, 93%-100%] vs 85% [95% CI, 74%-97%], P = .02), distant metastasis-free survival (100% [95% CI, 100%-100%] vs 80% [95% CI, 69%-94%], P < .01), disease-free survival (98% [95% CI, 93%-100%] vs 71% [95% CI, 59%-87%], P < .01), and overall survival (100% [95% CI, 100%-100%] vs 88% [95% CI, 79%-98%], P = .02). No late grade 3+ gastrointestinal or genitourinary toxicities were observed in the patients who underwent continued NOM. Short-course radiation therapy followed by consolidation chemotherapy may be a feasible organ preservation strategy in rectal cancer. Additional prospective studies are necessary to evaluate the safety and efficacy of this approach.

Cost-Effectiveness of Short-Course Radiation Plus Temozolomide for the Treatment of Newly Diagnosed Glioblastoma Among Elderly Patients in China and the United States.

Background: Glioblastoma multiforme (GBM) is a fatal type of brain tumor with a high incidence among elderly people. Temozolomide (TMZ) has proven to be an effective chemotherapeutic agent with significant survival benefits. This study aimed to evaluate the economic outcomes of radiotherapy (RT) and TMZ for the treatment of newly diagnosed GBM in elderly people in the United States (US) and China. Methods: A partitioned survival model was constructed for RT plus TMZ and RT alone among patients with methylated and unmethylated tumor status. Base case calculations and one-way and probabilistic sensitivity analyses were performed. Life-years, quality-adjusted life-years (QALYs), costs (in 2021 US dollars [$] and Chinese Yuan Renminbi [¥]), and incremental cost-effectiveness ratios (ICERs) were calculated. Results: RT plus TMZ was found to be associated with significantly higher costs and QALYs in all groups. Only US patients with methylated status receiving RT plus TMZ had an ICER ($89358.51) less than the willingness-to-pay (WTP) threshold of $100000 per QALY gained when compared with receiving RT alone. When the WTP threshold ranged from $100000 to $150000 from the US perspective, the probability of RT plus TMZ being cost-effective increased from 80.5 to 99.8%. The cost of TMZ must be lower than ¥120 per 20 mg for RT plus TMZ to be cost-effective among patients with methylated tumor status in China. Conclusion: RT plus TMZ was not cost-effective in China, and a reduction in the TMZ price was justified. However, it is highly likely to be cost-effective for patients with methylated tumor status in the US.

444 CORRELATION BETWEEN PATHOLOGIC COMPLETE RESPONSE TO NEOADJUVANT THERAPY AND RECURRENCE IN PATIENTS WITH ESOPHAGEAL CANCER

Abstract Multimodal treatment options in carcinoma esophagus include neoadjuvant chemoradiotherapy or chemotherapy followed by surgery. The degree of pathologic response to different neoadjuvant options and its impact on the oncologic outcome is a matter of debate. With this background we carried out this study to analyze the rate of pathologic complete re-sponse (pCR) and its effect on recurrence in patients with carcinoma esophagus treated with various combinations of neoadjuvant chemotherapy/radiotherapy and surgery. Methods The records of all patients with carcinoma esophagus registered in our clinics between June 2012 and December 2014 were retrieved from a prospectively maintained database and were analyzed. of the 70 patients with histologically proven esophageal cancer who were treated with curative intent during this period, those with pCR (15) were followed up for a minimum of 5 years. These 15 patients are the subjects of this study. Results Forty eight (48) patients received neoadjuvant chemotherapy (NACT), 16 were treated with short course radiotherapy (SRT), and 3 patients received neoadjuvant chemoradiation (CRT). Four patients developed metastatic disease on neoadjuvant therapy. 66 patients (63 after neoadjuvant therapy and 3 upfront) underwent transthoracic esophagect-omy. Pathological CR was seen 12 patients (25%) in NACT-surgery arm, 2 (12%) in SRT-surgery and 1 (33%) in CRT-surgery groups. Three patients had postoperative mortality due to pulmo-nary complications. At 5 yrs, 14 out of 15 patients with pathological CR are alive and disease free. One patient developed brain metastases after 3 years and died. Conclusion Neoadjuvant therapy followed by radical surgery is a safe and effective treatment option for the management of carcinoma esophagus. Pathologic CR strongly correlates with recurrence-free survival. The relative significance of pCR after different types of neoadjuvant therapies need to be tested in future studies.

Organ preservation following short-course radiotherapy for rectal cancer.

BackgroundNon-operative management of rectal cancer is increasingly being used in selected patients. Most reports include patients treated with chemoradiotherapy (CRT) before inclusion into a Watch & Wait (W&W) programme. The aim of this study was to report outcomes from a single-centre W&W programme involving a large cohort of patients.MethodsPatients treated with chemoradiotherapy (CRT) or short-course radiotherapy (SCRT) with or without chemotherapy, between 2008 and 2020, who showed signs of a clinical complete response (cCR) were reviewed. Patients were assessed using digital rectal examination, flexible endoscopy, carcinoembryonic antigen measurement, MRI, and CT imaging, discussed at the multidisciplinary tumour board meeting, and followed up in a dedicated W&W programme as from 2015. Outcomes including regrowth and 3-year survival (time to regrowth or death) were prospectively evaluated.ResultsOf 142 patients who were assessed, 88 fulfilled the criteria for cCR. Treatment before cCR included CRT, SCRT with chemotherapy, and SCRT alone in 16 (18 per cent), 28 (32 per cent), and 44 (50 per cent) patients, respectively. Patients treated with CRT and SCRT with chemotherapy had more advanced clinical T- and N-stage, compared with patients treated with SCRT alone (clinical T-stage > 2: 81 per cent and 89 per cent versus 47 per cent, respectively; clinical N-stage > 0: 75 per cent and 93 per cent versus 68 per cent, respectively). Overall rate of regrowth was 19 per cent, with 31 per cent, 21 per cent, and 14 per cent following CRT, SCRT with chemotherapy, and SCRT alone, respectively. Uni- and multivariable analyses evaluating the clinical parameters revealed no statistically significant associations with risk of local regrowth. All but one patient with regrowth underwent salvage surgery. The 3-year survival rate (death with regrowth as competing risk) was 93 per cent, with no significant difference between treatment groups.ConclusionIn this cohort of W&W patients, the vast majority received SCRT with or without chemotherapy and results consistent with previous W&W reports were obtained. No statistically significant differences in terms of regrowth rate were obtained when comparing CRT, SCRT with chemotherapy, and SCRT alone. SCRT can induce sustained cCR and may precede a W&W strategy.

1627P Management of locally advanced rectal cancer during the COVID-19 outbreak: First results of a shift towards short course neoadjuvant radiotherapy

Alike other tumor types, it was recommended that the management of locally advanced rectal cancer (LARC) during the COVID outbreak would shift towards hypofractionated RT schemes. Short-course neoadjuvant radiotherapy (SCRT) is comparable to long-course chemoradiation (CRT) in terms of toxicity and survival; nevertheless, CRT is still largely used, especially in advanced tumors. We aim to report the clinical-pathological characteristics and first treatment results of patients treated in a 3-month period during COVID-19 outbreak and to compare them to those treated in the previous year.

Pragmatic use of short-course radiotherapy, chemotherapy and surgery for stage IV rectal cancer with locally advanced or symptomatic primary tumours.

We assessed management of patients with de novo metastatic rectal cancer, referred for radiotherapy to the rectum, who were candidates for short-course radiotherapy (SCRT) and chemotherapy, followed by resection of all disease. We assessed surgical outcomes, overall survival (OS) and progression-free survival (PFS). Retrospective review of patients meeting criteria: (i) treatment with SCRT to rectum; (ii) locally advanced primary rectal cancer; and (iii) resectable distant metastases at diagnosis. Data were collected from charts, correspondence and electronic patient records. OS and PFS were calculated using the Kaplan-Meier method. Between 2016 and 2020, 48 patients with stage IV rectal cancer at diagnosis were treated with SCRT. Only 15 patients (31%) had resectable metastatic disease and were intended for SCRT (25 Gy/5#), then chemotherapy, followed by resection of all sites of disease and are included in our study. 12 of the 15 surgical candidates (80%) had rectal surgery as planned, and 11 of the 15 (73%) had resection of the rectal primary and all metastatic disease. One patient had a pathological complete response (pCR), and 50% of surgical patients had a Mandard TRG of 1 or 2. Median PFS and OS for the 15 surgical candidates were 12.6 and 25.2 months, respectively, with a median FU of 21.2 months. For this cohort of patients, our treatment paradigm is pragmatic and results in excellent pathological response. However, the effectiveness of this approach should be the subject of future prospective studies.

Total neoadjuvant therapy in patients with locally advanced rectal cancer: A tertiary medical center experience.

The current standard of care for locally advanced rectal cancer (LARC) includes preoperative chemoradiation, followed by total mesorectal excision and adjuvant chemotherapy. This multimodality treatment improves local control but is associated with low compliance rates without clear beneficial effects on overall survival (OS) and distant metastasis. In this retrospective study, the charts of patients diagnosed with cT3/4 or cT2-node-positive rectal cancer between January 2011 and June 2019 were reviewed. The chemoradiation therapy (CRT) group received a long course of CRT with capecitabine followed by surgery and adjuvant chemotherapy. The total neoadjuvant therapy (TNT) group received 6 cycles mFOLFOX and a short course of radiation therapy followed by surgery. A total of 81 patients were included, among which 55 (67.9%) received CRT and 26 (32.1%) received TNT. In the CRT group, 15 (27.3%) patients achieved pathologic complete response (pCR) compared with 10 (38.5%) in the TNT group (P=0.22). A total of 19 (35.8%) cases in the CRT group downstaged to pT0N0 or pT1N0 compared with 11 (42.3%) in the TNT group (P=0.33). The 2-year disease-free survival (DFS) rate was 81.0% in the TNT group and 84.0% in the CRT group (P=0.15). Out of 55 patients in the CRT group, 30 patients received adjuvant chemotherapy, 22 (40.0% of CRT cases) of which completed a full course. All 26 patients in the TNT group received neoadjuvant chemotherapy, where 22 (84.6%) patients took a full course (P<0.001). In conclusion, the present study revealed that patients treated with TNT were more compliant to chemotherapy than those treated with CRT. A numerically higher pCR rate, and nodal and tumor downstaging were noted in the TNT group without significance. No difference was noted in the 2-year DFS. Longer follow-up is required.

Short-course compared to long-course palliative radiotherapy for oesophageal cancer: a single centre observational cohort study

BackgroundCommon symptoms of oesophageal cancer are dysphagia, pain, and bleeding. These symptoms can be relieved with palliative radiotherapy. The aim of this study was to analyse the outcome of two different palliative radiotherapy schedules.MethodsWe conducted a retrospective cohort study on palliative radiotherapy for oesophageal cancer given at Karolinska University Hospital. Patients included were treated with either short-course (20 Gy in 4 Gy fractions daily, 5 consecutive workdays) or long-course (30–39 Gy in 3 Gy fractions, 10–13 consecutive workdays) palliative external beam radiotherapy between January 2009 and December 2013. The primary endpoint was dysphagia relief and secondary endpoints were adverse events, re-interventions, and overall survival. Cox regression analyses were used to estimate the effect of treatment schedule on survival.ResultsA total of 128 patients received external beam radiotherapy under the study period, of these 75 (58.6%) received short-course radiotherapy and 53 (41.4%) long-course radiotherapy. Sixteen (30.8%) patients experienced dysphagia relief after short-course radiotherapy and 9 (22.0%) patients after long-course radiotherapy (p = 0.341). Acute toxicity was less frequent after short-course radiotherapy than after long-course radiotherapy, particularly oesophagitis (35.4% vs. 56.0%, p = 0.027) and nausea/emesis (18.5% vs. 36.0% p = 0.034). Re-interventions tended to be more common after short-course radiotherapy (32.0%) than after long-course radiotherapy (18.9%) (p = 0.098). There was no difference in overall survival between the two groups.ConclusionsShort- and long-course palliative radiotherapy for oesophageal cancer were equally effective to relieve dysphagia and no difference was seen in overall survival. Acute toxicity was, however, more frequent and more severe after long-course radiotherapy. Our results suggest that short-course radiotherapy is better tolerated with equal palliative effects as long-course radiotherapy.

Neoadjuvant Modified Short-Course Radiotherapy Followed by Delayed Surgery for Locally Advanced Rectal Cancer.

Simple SummaryBoth short- and long-course neoadjuvant radiotherapy (NA-RT) followed by surgery have been adopted as standard treatments for locally advanced rectal cancer (LARC). We hypothesized that a modified short-course radiotherapy (mSC-RT) using an accelerated hyperfractionated regimen, with a dose of 2.5 Gy twice daily up to a total dose of 25 Gy in 10 fractions, can provide a favorable therapeutic ratio in comparison with the conventional regimens. Ninety-seven consecutive LARC patients undergoing mSC-RT followed by delayed surgery were analyzed in this retrospective study. Additionally, potential prognostic factors for overall survival (OS) were also assessed. The results showed that mSC-RT followed by delayed surgery achieved equivalent anti-tumor efficacy and acute toxicity that were comparable with long- and short-course NA-RT, respectively. A neutrophil-to-lymphocyte ratio (NLR) ≥ 1.83 was independently associated with poor OS in LARC patients receiving mSC-RT. Thus, mSC-RT can be a promising alternative to both standard long- and short-course NA-RT regimens.This study aimed to assess the clinical outcomes and predictive factors of neoadjuvant modified short-course radiotherapy (mSC-RT) for locally advanced rectal cancer (LARC). Data from 97 patients undergoing mSC-RT followed by radical surgery for LARC were retrospectively analyzed. A 2.5 Gy dose twice daily up to a total dose of 25 Gy in 10 fractions was administered through mSC-RT, and this was delivered with oral chemotherapy in 95 (97.9%) patients. Radical surgery was performed 6 (range, 3–13) weeks after mSC-RT. The median follow-up among surviving patients was 43 (8–86) months. All patients completed neoadjuvant radiotherapy with no acute toxicity grade ≥ 3. Three- and five-year local control rates were 96.3% and 96.3%, respectively. Three- and five-year overall survival (OS) rates were 92.7% and 79.8%, respectively. Univariate analyses revealed that poor OS was associated with no concurrent administration of capecitabine, C-reactive-protein-to-albumin ratio ≥ 0.053, carcinoembryonic antigen ≥ 3.4 ng/mL, and neutrophil-to-lymphocyte ratio (NLR) ≥ 1.83 (P = 0.045, 0.001, 0.041, and 0.001, respectively). Multivariate analyses indicated that NLR ≥ 1.83 was independently associated with poor OS (p = 0.018). mSC-RT followed by delayed surgery for LARC was deemed feasible and resulted in good clinical outcomes, whereas poor OS was associated with high NLR.

Optimal neoadjuvant strategy for signet ring cell carcinoma of the rectum-Is TNT the solution?

The results of total neoadjuvant therapy (TNT) for locally advanced rectal cancers (LARC) cannot be extrapolated to signet-ring cell cancers (SRCC) that have an extremely aggressive biology. A retrospective study comparing long course chemoradiation (CTRT) against short course radiation (SCRT) and 12 weeks of chemotherapy for high-risk LARC. Primary endpoints were treatment failure and disease-free survival (DFS) RESULTS: CTRT was given to 74 (59.7%) and SCRT/Chemotherapy to 50 patients (40.3%). Additional chemotherapy was required in 54.1% and 28%, respectively. Except for nodal staging, no other MRI parameter down-staged. Treatment failures were seen in 33.9% and 25.8% had progression. The peritoneum was the commonest site of progression (59.4%). Of the patients that were surgically explored, 63.7% had R0 resections and pathological complete response was seen in 9.7%. At a median follow-up of 35 months, 56.5% had DFS events with a 3-year DFS of 39.5%. Recurrences were noted in 45.1% after curative resections and the 3-year OS/DFS of these patients were 67.2%/56.4%. On multivariate regression, the type of preoperative therapy did not influence treatment failures or DFS. SRCC is a very aggressive disease and none of the treatment strategies could show superiority over the other with very high peritoneal progression rates and relapses.