Neoadjuvant RT Research Articles

Hypofractionated Radiation Therapy: A Cross-sectional Survey Study of US Radiation Oncologists.

For many malignancies, hypofractionated radiotherapy (HFRT) is an accepted standard associated with decreased treatment time and costs. United States provider beliefs regarding HFRT likely impact its adoption but are poorly studied. We surveyed US-based radiation oncologists (ROs) to gauge HFRT utilization rates for prostate (PC), breast (BC), and rectal cancer (RC) and to characterize the beliefs governing these decisions. From July to October 2021, an anonymized, online survey was electronically distributed to ROs actively practicing in the United States. Demographic and practice characteristic information was collected. Questions assessing rates of offering HFRT for PC, BC, and RC and perceived limitations towards using HFRT were administered. A total of 203 eligible respondents (72% male, 72% White, 53% nonacademic practice, 69% with 11+ years in practice) were identified. Approximately 50% offered stereotactic body radiation therapy (SBRT) for early/favorable intermediate risk PC. Although >90% of ROs offered whole-breast HFRT for early-stage BC, only 33% offered accelerated partial-breast irradiation (APBI). Overall, 41% of ROs offered short-course neoadjuvant RT for RC. The primary reported barriers to HFRT utilization were lack of data, inexperience, and referring provider concerns. HFRT is safe, effective, and beneficial, yet underutilized-particularly prostate SBRT, APBI, and short-course RT for RC. Skills retraining and education of ROs and referring providers may increase utilization rates.

Neoadjuvant nivolumab plus paclitaxel/cisplatin- chemo-radiotherapy (neo-NTP-CRT) followed by esophagectomy for locally advanced esophageal squamous cell carcinoma (ESCC): A phase II study.

e16098 Background: Adjuvant nivolumab has shown efficacy in reducing recurrence in patients (pts) with locoregional esophageal cancer harboring pathologic residual disease following neoadjuvant chemoradiotherapy (CRT). However, the efficacy of adding nivolumab to neoadjuvant CRT remains unclear. Methods: We conducted a phase II trial of neoadjuvant nivolumab (240mg IV on D-14, 1, 15, 29), paclitaxel (50mg/m2 IV on D1, 8, 15, 22, 29), cisplatin (30mg/m2 IV on D1, 8, 15, 22, 29) and RT (45Gy given in 25 fractions) followed by esophagectomy 6 to 8 weeks after finishing CRT in pts with locally advanced ESCC, defined as clinical stage cT3-4aN0M0 or cT1-3N1-3M0 according to the AJCC Cancer Staging System 8th ed. (ClinicalTrials.gov Identifier: NCT05130684). The study, in a Simon’s two-stage design, used pathological complete response (pCR) rate as the primary endpoint. Secondary endpoints included feasibility, safety, recurrence free survival (RFS), progression free survival (PFS), and overall survival (OS). Results: Between Jan 2021 and Apr 2023, we enrolled a total of 17 pts. Fifteen were male. The median age was 52 years (range: 44~69). The clinical stage was I, II, and III in 1, 1, and 15 pts, respectively. All pts received neo-NTP-CRT with the following dose-intensities (mean dose intensity [range]): nivolumab (95% [50%~ 100%]), paclitaxel (75% [48%~ 100%], cisplatin (97% [80%~ 100%]), and radiotherapy (100%). Fourteen pts received esophagectomy, and 4 of them achieved pCR (24%). Because pCR for the first stage did not meet the efficacy criteria to move forward to second-stage, the enrollment was discontinued after enrolling 17 pts. During neo-NTP-CRT, the most common treatment-related adverse events (TRAEs) were leukopenia (76%), neutropenia (59%), thrombocytopenia (35%), and skin rash (35%); and the most common grade 3 and 4 TRAEs were leukopenia (24%), neutropenia (6%), and nausea and vomiting (6%). Among 14 pts receiving esophagectomy, 4 experienced surgical complications, including 2 with anastomotic leakage, 1 with subclavian artery rupture, and 1 with pneumonitis; one pt died 263 days after surgery, followed by a prolonged hospital stay due to refractory anastomotic leakage, infectious complications, and tumor progression. The median follow-up duration was 18 months. Median RFS, PFS and OS was 8, 12, and 16 months, respectively. Conclusions: Our data indicate that adding nivolumab to neoadjuvant paclitaxel and cisplatin-based CRT is feasible but does not improve pCR rate in locally advanced ESCC pts. Clinical trial information: NCT05130684 .

Resilience in Rectal Cancer Treatment: Lessons from the COVID-19 Era in Czech Republic.

The management of patients with COVID-19 infection has placed great pressure on the healthcare systems around the world. The aim of this study was to investigate the impact of the COVID-19 pandemic on the treatment outcomes of patients with rectal cancer by comparing them to those of patients with the same diagnosis in the pre-pandemic period. Retrospective data analysis of patients undergoing multimodal treatment for rectal cancer at the four university hospitals during the COVID-19 pandemic (2020-2021) and the 2-year pre-pandemic period (2018-2019). A total of 693 patients (319 in the pre-pandemic period and 374 in the pandemic period) with rectal cancer were included in the study. The demographic and clinical characteristics of patients in both study periods were comparable, as was the spectrum of surgical procedures. Palliative surgery was more common in the pandemic period (18% vs 13%, p=0.084). The proportion of patients undergoing minimally invasive surgery was higher during the COVID-19 pandemic (p=0.025). There were no statistically significant differences between the study periods in the incidence/severity of post-operative complications, 30-day mortality and length of hospital stay. The number of positive resection margins was similar (5% vs 5%). Based on these results, COVID-19 had no effect on the postoperative morbidity and mortality in patients undergoing surgery for rectal cancer. Neoadjuvant treatment was more common in the pre-pandemic period (50% vs 45%). Long-course RT was predominantly offered in the pre-pandemic period, short-course RT during the pandemic. Significantly shorter "diagnosis-surgery" intervals were observed during the pandemic (23 days vs 33 days, p=0.0002). The "surgery-adjuvant therapy" interval was similar in both analysed study periods (p=0.219). Our study showed, that despite concerns about the COVID-19 pandemic, multimodal treatment of rectal cancer was associated with unchanged postoperative morbidity rates, increased frequency of short-course neoadjuvant RT administration and shorter "diagnosis-surgery" intervals.

Neoadjuvant Radiotherapy Is Associated with Fewer Acute Adverse Skin Reactions Without Increased Risk of Postoperative Wound Complications in High-Grade Extremity Soft Tissue Sarcoma - A Retrospective Comparative Study with A Mean Follow-Up of 7 Years

Aim: In this study, we aim to compare the adverse effects and oncological outcomes of patients with high-grade extremity soft tissue sarcoma receiving neoadjuvant or adjuvant RT. Methods: From 2008 to 2022, Sixty-four patients underwent limb-preserving surgery in our institute for localized high-grade extremity soft tissue sarcoma were included. Thirty-nine patients received adjuvant radiotherapy while twenty-five patients received neoadjuvant RT before surgery if the soft tissue sarcomas were close to the neurovascular bundles, bones or histological types of myxoid liposarcoma or rhabdomyosarcoma. Primary outcomes were acute RT-related skin adverse reactions and significant side effects comprising postoperative wound complications, pathological fractures and RT-induced sarcoma. Secondary outcomes included surgical margin quality, Local-Recurrence (LR)-free survival, metastasis-free survival and overall survivorship. Results and Discussion: Patients in the neoadjuvant RT group had significantly fewer acute RT-induced adverse skin reactions than the adjuvant RT group (p=0.044, Table 2). None in the neoadjuvant RT group suffered severe acute skin reaction (RTOG grade 3-4). Wound infection (n=2) and pathological fracture (n=1) were rare in both adjuvant and neoadjuvant RT groups (P=0.640 & 1.000 respectively). Survival curves for local-recurrence-free survival, metastasis-free survival and overall survivorship of both neoadjuvant and adjuvant groups were analyzed via Kaplan-Meier Curve. All results are statistically insignificant, with p=0.835, 0.948 and 0.540, respectively. Presence of metastasis was the only statistically significant predictor of the overall survival-adjusted hazard ratio of 8.7 (95%CI 2.7-28), p<0.001. Conclusion: Patients with neoadjuvant RT had lower cumulative radiation doses and fewer acute adverse skin reactions. There was no increased risk of postoperative wound complication compared to adjuvant RT. The LR-free survival, metastasis-free survival and overall survival were comparable in both groups. Our results suggested that postponing surgery to eight weeks after neoadjuvant RT and primary wound closure were associated with fewer wound complications, but further studies were warranted.

Preoperative Radiotherapy of Soft Tissue Sarcoma with Simultaneous Integrated Boost: A Phase II Study

Neoadjuvant radiotherapy to 50 Gy in 25 fractions is delivered in operable Soft Tissue Sarcoma (STS) patients to downstage the tumor and improve resectability, although at the expense of increased risk of wound dehiscence. Nonetheless, clear margin resection (R0) may not be achieved in tumors located in proximity of critical structures such as the neurovascular bundle (NVB), resulting in impaired local control. The aim of this study is to increase R0 rate through addition of an IMRT boost to the potential sites of suboptimal resection in STS patients receiving neoadjuvant RT. We report hereby the dosimetric results and safety results from the first 5 patients enrolled in this trial. We designed a prospective monocentric interventional single-arm Phase II study enrolling locally advanced STS eligible for surgery. RT is administered in 25 daily fractions to include the MRI-based Gross Tumor Volume (GTV) and peritumoral tissue at risk of microscopic spread (CTV1) to a dose of 50 Gy (2Gy/fraction), with SIB (Simultaneous Integrated Boost) intensification to the tumor/dissection plane interface (CTV2) to a dose of 60 Gy (2.4 Gy/fraction). CTV2 delineation is approved by both a Radiation Oncologist and Surgeon. A margin of 0.5 cm is applied to both CTV to obtain PTV1 and PTV2. Concurrent anthracyclines-based chemotherapy (ChT) is allowed up to 3 cycles. Primary endpoint is R0 resection rate. Secondary endpoints include pathologic complete response rate, objective response rate, overall survival, local and distant progression-free survival, acute and chronic toxicity rate. To assess an increase in R0 rate from 81% to 97% assuming β = 80% e α = 0.05, 33 patients will be included. Dose constraints are summarized in Table1. At least 95% of the PTV1 and PTV2 should be covered by 95% the prescription dose up to a maximum allowed dose of 107%. Five patients were included. Tumor was located in the limbs and in the trunk in respectively 4 and 1 patient. Mean age was 47 years (range: 19-67). Concurrent chemotherapy was performed in 2 patients. Mean GTV size was 228.6 cm3 (range: 59.8-314.5). Mean PTV coverage by the 95% of the dose prescription was 98% (95-100) and 97% (95-100) in PTV1 and PTV2, respectively. Mean PTV1 and PTV2 Dmax were 61.6 Gy (range: 59-63) and 64.1 Gy (range:63-66), in both cases below the 107% threshold. Mean Bone Dmax was 55 Gy (56.6-61.8 Gy). Dmax to the skin corridor exceeded 20 Gy in 1 patient (range 12.5-58.1). While the NVB was overlapping the PTV2 in all cases, Dmax was below 66 Gy. At the time of this report, no Grade ≥3 acute skin toxicity was observed. Two patients underwent surgery with a radiological partial response (RECIST) and pathological complete response. No major wound complication was reported. Planning goals of the first 5 enrolled patients are achieved in most cases. Preliminary results show a benign safety profile and promising tumor response rate.

Pelvic insufficiency fractures and pelvic bone metastases after neoadjuvant (chemo)radiotherapy for rectal cancer

Background: Pelvic insufficiency fractures (PIFs) are a late complication of radiotherapy for pelvic malignancies. We evaluated the incidence, radiologic findings, clinical course, and outcome of PIFs in patients treated with neoadjuvant (chemo)radiotherapy ((C)RT) for rectal cancer. Material and methods: Data of patients diagnosed with rectal cancer from a large teaching hospital treated from 2002 to 2012 were extracted from the Dutch Cancer Registry. All hospital records were reviewed for the diagnosis of PIFs or pelvic bone metastases. An expert radiologist reassessed all imaging procedures of the lower back, abdomen, and pelvis. Results: A total of 513 rectal cancer patients were identified of whom 300 patients (58.5%) were treated with neoadjuvant (C)RT (long- vs. short-course radiotherapy: 91 patients [17.7%] vs. 209 [40.7%], respectively). Twelve PIFs were diagnosed initially according to hospital records and imaging reports of all 513 patients. These 12 patients were treated with neoadjuvant (C)RT. After reassessment of all pelvic imaging procedures done in this patient group (432 patients (84.2%)), 20 additional PIFs were detected in patients treated with neoadjuvant (C)RT, resulting in a 10.7% PIF rate in irradiated patients. One PIF was detected in the group of patients not treated with neoadjuvant (C)RT for rectal cancer. This patient had palliative radiotherapy for prostate cancer and is left out of the analysis. Median follow-up time of 32 PIF patients was 49 months. Median time between start of neoadjuvant (C)RT and diagnosis of PIF was 17 months (IQR 9–28). Overall median survival for patients with PIF was 63.5 months (IQR 44–120). Conclusion: PIFs are a relatively common late complication of neoadjuvant (C)RT for rectal cancer but are often missed or misdiagnosed as pelvic bone metastases. The differentiation of PIFs from pelvic bone metastases is important because of a different treatment and disease outcome.

PCR and 2-Year Disease-Free Survival: A Combination of the Two Endpoints as a New Classification for Locally Advanced Rectal Cancer Patients—An Updated Pooled Analysis of Eleven International Randomized Trials

LARC is managed by multimodal treatments whose intensity can be highly modulated. In this context, we need surrogate endpoints to help predict long-term outcomes and better personalize treatments. A previous study identified 2yDFS as a stronger predictor of OS than pCR in LARC patients undergoing neoadjuvant RT. The aim of this pooled analysis was to assess the role of pCR and 2yDFS as surrogate endpoints for OS in a larger cohort. The pooled and subgroup analyses were performed on large rectal cancer randomized trial cohorts who received long-course RT. Our analysis focused on the evaluation of OS in relation to the pCR and 2-year disease status. A total of 4600 patients were analyzed. Four groups were identified according to intermediate outcomes: 12% had both pCR and 2yDFS (the better); 67% achieved 2yDFS but not pCR (the good); 1% had pCR but not 2yDFS; and 20% had neither pCR nor 2yDFS (the bad). The pCR and 2yDFS were favorably associated with OS in the univariate analysis, and 2yDFS maintained a statistically significant association in the multivariate analysis independently of the pCR status. The combination of the pCR and 2yDFS results in a strong predictor of OS, whereas failure to achieve 2yDFS carries a poor prognosis regardless of the pCR status. This new stratification of LARC patients could help design predictive models where the combination of 2yDFS and pCR should be employed as the primary outcome.

Single Fraction vs. Fractionated Preoperative Radiosurgery for Resected Brain Metastases: A PROPS-BM Multicenter Cohort Study

<h3>Purpose/Objective(s)</h3> Preoperative (preop) stereotactic radiosurgery (SRS) is a feasible alternative to postoperative (postop) SRS with potential benefits in adverse radiation effect (ARE) and meningeal disease compared to postop SRS. Most reported studies of preop SRS utilized single fraction (fx) SRS. The goal of this study was to compare outcomes and toxicity of single fraction preop SRS with fractionated (3-5 fx) preop stereotactic radiotherapy (FSRT). <h3>Materials/Methods</h3> Patients (pts) with brain metastases (BM) from solid cancers, of which at least 1 lesion was treated with preop SRS or FSRT and underwent planned resection were included from 6 institutions. SRS to synchronous intact BM was allowed. Exclusion criteria included classically radiosensitive or non-solid cancers and prior or planned whole brain radiotherapy. RT dose, fractionation, and interval between preop RT and surgery was per individual institutional protocol. Intracranial outcomes were estimated using cumulative incidence with competing risk of death. Propensity score matched (PSM) analyses were performed. <h3>Results</h3> The cohort included 378 pts with 389 preop RT treated index lesions. Most pts had non-small cell lung (47.9%), breast (16.1%), or melanoma (11.4%) cancer. The majority of pts (61.1%) had a single BM and 95.4% underwent gross total resection (GTR). SRS was used for 328 (84.3%) lesions with FSRT used for 61 (15.7%). Most FSRT (93.4%) was 3 fx, with the remainder being 5 fx. Median prescribed dose for FSRT and SRS was 24 Gy and 15 Gy, respectively. There were baseline imbalances between cohorts. The FSRT cohort had significantly more use of planning target volume (PTV) margin expansion > 1 mm (64% vs. 5.2%), more pts with multiple BM (54% vs. 38%), and larger median gross tumor volume (GTV, 12.3 cc vs. 9.7 cc). In univariate analysis, preop FSRT was associated with significantly lower rate of cavity local recurrence (LR) than SRS (1-year: 2.8% vs. 14.1%, p=0.02). PSM yielded 57 matched pairs. There were no significant residual imbalances in the PSM cohorts. Median imaging FU period was 8 months for both groups. FSRT was associated with significantly lower cavity LR compared with SRS (1-year: 3% vs. 17.9%, p=0.02). There were no differences in ≥ grade 2 ARE (7.4% vs. 4.9%, p=0.34), meningeal disease (2% vs. 4%, p=0.81), or distant brain failure (21.8% vs. 37.4%, p=0.25). No grade 3 - 5 ARE events occurred. Overall survival (OS) was significantly higher with FSRT in PSM analysis as well (1-year: 71.2% vs. 52.1%, p=0.04). <h3>Conclusion</h3> Preop FSRT (3-5 fx) is associated with significantly reduced risk of cavity LR and improved OS compared with preop single fx SRS. Both preop FSRT and SRS show notably low rates of ARE and meningeal disease. Three fx preop FSRT may be a preferred option for neoadjuvant RT of larger or higher risk lesions. Additional confirmatory studies are needed. A randomized trial of preop SRS versus postop SRS is currently being designed (NRG BN012).

PO-1319 Neoadjuvant RT dose escalation for LARC in the new era of radiotherapy; a review of literature

PO-1319 Neoadjuvant RT dose escalation for LARC in the new era of radiotherapy; a review of literature

Intraoperative radiotherapy with a photonic radiosurgical system in the treatment of locally advanced rectal cancer

Aim of the study: to evaluate the results of using intraoperative radiotherapy (IO RT) in patients with locally advanced rectal cancer (RC).Material and Methods. A total of 172 patients with histologically confirmed stage II –III (pT3–4 or pN+) RC were included in this retrospective analysis; of those, 92 (53,5 %) were treated with IO RT alone and 80 (46,5 %) received both neoadjuvant EBRT and IO RT. The median follow-up was 25 months for the IO RT group and 22 months for the EBRT/IO RT group (p=0,52).Results. The incidence of toxicity was low in both groups with an overall complication rate of 5,4 %. There were no statistically significant differences between both groups in 4-year overall survival rates (59,1 % in the IO RT group versus 67,4 % in the EBRT / IO RT group, p=0,66), progression-free survival (53,6 versus 55,1 %, p=0,51) and local progression free survival (59,4 versus 65,4 %, p=0,70).Conclusion. IO RT for locally advanced RC is a safe method that ensures adequate local control and can be considered as an effective treatment method both in an isolated version and in integration into a multimodal treatment algorithm in a specialized oncological clinics.

Interaction Between Neutrophil-to-Lymphocyte Ratio, Radiotherapy Fractionation/Technique, and Risk of Development of Distant Metastasis in Locally Advanced Rectal Cancer Patients

There is a paucity of data studying the significance of neutrophil-to-lymphocyte ratio (NLR) in peripheral blood of patients with locally advanced rectal cancer (LARC) planning to undergo preoperative RT. We aimed to investigate the prognostic impact of NLR in patients with LARC and whether there are modifiable factors in RT which influencing the level of NLR.We studied 1366 patients treated with neoadjuvant RT with concurrent or sequential chemotherapy for LARC from 2006 to 2019. Most (97.8%) were treated with long-course RT (50-50.4 Gy in 25-28 fractions) with 3DCRT (n = 851) or helical tomotherapy (n = 504). Short-course RT (25 Gy in 5 fractions, followed by 6-week XELOX) was used in 30 cases (NCT03676517). The absolute neutrophil and lymphocyte counts were obtained from the sample collected at the time of initial diagnosis, before and during the course of preoperative RT and before surgery. The primary endpoint was distant metastasis-free survival (DMFS).With the median follow-up time of 61.3 months (4.1-173.7 months), the 5-year DMFS was 80.1%. 5-year DMFS was significantly associated with the level of NLR after RT, but not with the level of NLR before RT. In Cox multivariate model, post-RT NLR greater than 4 was independently correlated with worse DMFS (HR 1.37, 95% CI, 1.08-1.73), along with higher icT stage, ypT stage and ypN stage. The 5-year OS of patients with post-RT NLR > 4.0 was 83.2%, compared to 94.4% in post-RT NLR ≤ 4 patients (P < 0.001). Increased level of post-RT NLR (> 4.0) was more frequently developed after long-course RT (OR, 2.77, P = 0.032) or helical tomotherapy (OR, 1.29, P < 0.001). Local recurrence risk, pathologic complete response rate and neoadjuvant rectal score were not significantly differed by the level of NLR (all P > .05).Elevation of NLR after neoadjuvant RT is associated with increased risk of DM development and poor OS in LARC. Development of high NLR following RT is directly related to RT fractionation and delivery modality, and tumor characteristics. Incorporation of SCRT with 3D-CRT or active bone marrow sparing-IMRT may be a modifiable factor that can indirectly affect DMFS by means of attenuating NLR in LARC patients, which needs further investigations.

Effect of delaying surgery by more than 10weeks after neoadjuvant therapy in rectal cancer: a single institution experience.

The optimal timing of surgery after neoadjuvant chemoradiotherapy (CRT) in locally advanced rectal cancer is still controversial. Aim of this study was to evaluate the effect of increasing time interval between the end of CRT and surgery on pathological outcomes. This is a retrospective analysis on 114 patients treated with long-course neoadjuvant RT with or without chemotherapy between January 2005 and September 2020. 43 patients underwent surgery within 10weeks from the end of CRT (1st group), whereas 71 patients underwent total mesorectal excision with a time interval equal or greater than 10weeks (2nd group). Primary endpoint was pCR (pathological complete response). Secondary endpoints were near pCR (ypT0-1 N0), tumor downstaging (ypT less than cT), nodal downstaging (ypN less than cN), and overall response comparing clinical with pathological TN stage. Overall, the pCR rate was 8.8%, whereas we observed no significantly difference in primary endpoint between the two groups. Considering near pCR, a trend toward significant difference in favor of 2nd group was seen (p = 0.072). Tumor and nodal downstaging rates were 39.5%, 41.9%, 59.2%, and 56.3% in the 1st and 2nd group, respectively, with a statistically significant difference for T category (p = 0.042). Overall response rates (TN stage) showed a trend toward significant difference in favor of patients of the ≥ 10week group (p = 0.059). Our study suggests that a prolonged time interval between the end of CRT and surgery (≥ 10weeks) increases pathological response rates.

PO-0958: Neoadjuvant RT followed by mastectomy and immediate breast reconstruction: updated 5-years results

PO-0958: Neoadjuvant RT followed by mastectomy and immediate breast reconstruction: updated 5-years results

Investigation of Practice Patterns in Elderly Patients with Locally Advanced Rectal Cancer and Prediction of Survival by a Validated Model

Rectal cancer is one of the most common malignant tumors in China and the world, with more than half of the patients aged ≥70 years at the time of diagnosis. However, the optimal treatment strategies in elderly patients with locally advanced rectal cancer (LARC) are still controversial. We designed our study to delineate the pattern of treatment for elderly LARC and analyze the risk factors that affect their overall survival (OS), and provide a basis for further analysis of decision-making for treatment of elderly patients. We retrospectively analyzed 187 elderly patients (≥70 years ) with LARC, who had received surgeries in our institution between January 2008 and December 2018, to evaluate the OS of four subgroups of patients according to four different treatment modalities: surgery only, neoadjuvant (C)RT, adjuvant (C)RT and adjuvant chemotherapy (no RT) and compared with 11,347 elderly LARC patients from the Surveillance, Epidemiology, and End Results (SEER)- registered database between 2004 and 2016. We also established a nomogram for predicting OS, which was evaluated by Harrell’s concordance index (C-index) and calibration plots in both training and validation cohort. 187 elderly patients with LARC in our institution were more frequently treated with only received surgery (49.2%) ,9.1% of patients received neoadjuvant (chemo)radiotherapy, adjuvant (C)RT and adjuvant chemotherapy (no RT) accounted for 18.7% and 23%, respectively. In the SEER cohort, surgery alone (41.8%) was also the main treatment strategy. The treatment patterns of the two cohorts were significantly different (P <0.001), especially in the application of radiation therapy (P <0.001). The 5-year overall survival (OS) was 45.0% in surgery only, 77.1% in n(C)RT, 54.6% in adjuvant (C)RT and 61.7% in adjuvant chemotherapy (no RT), which had significant difference in univariate and multivariate Cox regression (P < 0.05). The C-index of the Nomogram model based on independent predictive factors and the calibration curve showed a high degree of agreement between the predicted and actual survival rates. The survival results of elderly LARC patients in our institution are similar to the clinical data of the SEER database during the same period, but there is a large gap in the treatment patterns, especially the application of radiation therapy. Radical surgery after neoadjuvant (chemo)radiotherapy may be the best treatment strategy for elderly patients with LARC, but individual analysis and appropriate adjustments still need to be made according to comorbidities and treatment benefits. The proposed nomograms based on independent clinicopathological variables may be practical and helpful for precise evaluation of patient prognosis, and guiding the individualized treatment for elderly LARC.

Neoadjuvant Short Course Radiation Therapy (SCRT) Followed By Chemotherapy And Delayed Surgery In Locally Advanced Rectal Adenocarcinoma: Initial Trends And Outcomes From Asian Population Cohort

Neoadjuvant short course RT (scRT) and chemotherapy followed by delayed surgery and adjuvant completion chemotherapy have been hypothesized to increase the pathological complete response (pCR), decrease distant failures and improve survival in locally advanced rectal cancer patients. Patients who have undergone scRT from November 2018 till July 2019 have been included in an intention to treat analysis. They received 25Gy/5fractions/5 days followed by FOLFOX based chemotherapy for 4-6 cycles followed by surgery and completion chemotherapy. Radio-biological evaluation was done by PET MRI at baseline and after completion of 4 cycles of chemotherapy. Inclusion criteria was locally advanced T3/T4, N0/N+ lesions including synchronous liver only metastasis patients. The primary endpoint is complete pathological response (cPR). Secondary endpoints are survival analysis, toxicity evaluation, additional radiological/ biological response grading and analysis. 65 patients were enrolled of whom 50 completed scRT.T3 disease was 86% (43/50) and T4, 14% (7/50). All except 3 (94%) had node positive on MRI.20% (10/50) had liver only metastatic disease and 80% (40/50) had locoregional disease. Local radical surgery was done in 52% (26/50) patients: 3/10 in the metastatic group after hepatic resection and 23/40 in non-metastatic group. In the metastatic cohort: 5 patients had progressive disease (PD) and 2 were lost to follow up (LFU). In non-metastatic cohort: 5 patients refused for surgery, 6 patients were LFU and 6 had PD. Surgery was done in 26 patients: 12/26 had ELAPE, 3/26 had APR, 9/26 had LAR and 2/16 had total proctocolectomy. All achieved negative resection margins. AJCC pathological tumor regression grade (pTRG) was assessed: 9/26(34.6%) had pTRG 0 (Complete response), 10/26(38.4%) patients had pTRG 1 (Moderate/significant response), 7/26(27%) had pTRG 2 (Minimal response), 0/26 (0%) had pTRG3 (Poor response). 8 patients had pathological node positivity. in which 62.5% (5/8) had a minimal response (TRG2), 25% (2/8) had pTRG1 and 12.5% (1/8) patient had pTRG0.PNI positivity in surgical specimen seen in 2/16 patients who had liver only metastasis and had minimal response (TRG2). GI toxicity was assessed in terms of diarrhea, pain abdomen, need for admission. Grade 2/3 neutropenia was seen in 49% of patients during chemotherapy. MRTRG& ADC value change in MRI and biological SUV change in PET were statistically analyzed in pretreatment and post neoadjuvant RT + chemotherapy scans. All parameters were correlated with pTRG and pathological T staging but none had a direct significant correlation (p<0.05) In our study, scRT followed by adjuvant chemotherapy and a delayed surgery, achieved high complete and near complete pathological response rates (73%). Such regimen looks promising and has the potential to change management paradigm in near future. Post-surgical complication rates, survival analysis and other late effects are awaited.

Neoadjuvant (chemo)radiotherapy and Lateral Node Dissection: Is It Mutually Exclusive?

The importance of total mesorectal excision (TME) has been the global standard of care in patients with rectal cancer. However, there is no universal strategy for lateral lymph nodes (LLN). The treatment of the lateral compartment remains controversial and has gone to the opposite directions between Eastern and Western countries in the past decades. In the East, mainly Japan, surgeons consider LLN metastases as regional disease and have performed TME with lateral lymph node dissection (LLND) without neoadjuvant (chemo)radiotherapy ([C]RT) in patients with clinical Stage II/III rectal cancer below the peritoneal reflection. In the West, neoadjuvant radiotherapy or has been the standard, and surgeons do not perform LLND assuming the (C)RT can sterilize most lateral lymph node metastasis (LLNM). Recent evidences show that lateral nodes are the major cause of local recurrence after (C)RT plus TME, and LLND reduces local recurrence particularly from the lateral compartment. Probably a combination of the two strategies, that is, neoadjuvant (C)RT plus LLND, would be needed to improve outcomes in patients with lateral nodal disease.

Patterns of Recurrence in Locally Advanced Resectable Oesophageal Carcinoma: Retrospective Review from a Tertiary Cancer Centre in South India.

The study aims to analyse patterns of recurrence following neoadjuvant treatment and surgery in carcinoma oesophagus with an intent to postulate optimal nodal radiation. A retrospective review of patients who presented to our centre within a 5-year period (2014-2018), with recurrence following sequential neoadjuvant treatment and radical surgery, was conducted in this single-institution study. The patterns of recurrence and duration of disease-free survival were analysed. Twenty-one patients (14 men, 7 women) presented with recurrence, of which 13, 7, and 1 patient(s) had received NACT, NACTRT, or both, respectively. Six patients who did not receive neoadjuvant radiotherapy received adjuvant RT. Among the 10 patients who had nodal recurrence after RT (either neoadjuvant or adjuvant), 6 and 4 patients had in-field and out-of-field nodal recurrences, respectively-the latter were equally distributed within 5cm and outside 5cm of the PTV margin. Among the patients who presented with recurrence, more than half had not received neoadjuvant RT (treated in the 'pre-CROSS era' or due to long-segment disease), reasserting the therapeutic superiority of NACTRT. Increased regularity of recurrences in the draining nodal region was not noted in this study, but large-scale, prospective, randomised head-to-head comparative trials to determine optimal nodal irradiation in carcinoma oesophagus are required.

Quality of life after rectal-preserving treatment of rectal cancer

AimRectal-preserving strategies for managing rectal cancer are becoming more common for selected groups of patients. Oncological outcomes are similar, so long as patients are closely followed, and any local recurrence detected and managed promptly. Functional outcomes are now of increasing importance so patients can be appropriately counselled prior to treatment. We examine functional outcomes in patients managed by multimodal organ-preservation approaches allowing comparison of the full range of strategies. Materials and methodsPatients attending for surveillance after any of four rectal-preserving treatments for rectal cancer (radiotherapy [RT], local excision [LE], RT then LE or LE then RT) were asked to complete a questionnaire assessing general quality of life and bowel, urinary and sexual function. Results100 patients completed questionnaires: 34 managed by neoadjuvant RT followed by ‘watch and wait’, 40 by LE, and 26 who had composite treatment (18 LE + RT and eight RT + LE). Questionnaires were completed a median of 10 months (IQ range 6–33) following treatment. The LE only group tended to have better bowel function, while the composite groups fared worse; significant differences were noted in LARS and some bowel symptoms scores. ConclusionBowel function appears better after LE alone compared with treatment strategies involving RT, and composite treatments have an additive effect on outcome impairment. Overall quality of life outcomes are good, despite the ongoing requirement for surveillance. As these treatments become more common it is important that patients can be better informed before deciding on a management pathway.

Tumour response 3 months after neoadjuvant single-fraction radiotherapy for low-risk breast cancer.

Standard treatment for early-stage invasive breast cancer (bca) consists of breast-conserving surgery and several weeks of adjuvant radiotherapy (rt). Neoadjuvant single-fraction rt is a novel approach for early-stage bca. We sought to investigate the effect of delaying surgery after neoadjuvant rt with respect to the rate of pathologic response (pr). Women 65 years of age or older with a new diagnosis of stage i luminal A bca were eligible for inclusion. A single 20 Gy dose to the primary breast tumour was given, followed by breast-conserving surgery 3 months later. The primary endpoint was the pr rate assessed by microscopic evaluation using the Miller-Payne system. To date, 10 patients have been successfully treated. Median age of the patients was 72 years (range: 65-84 years). In 8 patients, neoadjuvant rt resulted in a tumour pr with median residual cellularity of 3%. No immediate rt complications other than mild dermatitis were noted. This study demonstrates a method for delivering single-fraction rt that can lead to a high level of pr in most patients. Continued accrual to this study and subsequent trials are needed to determine the feasibility, safety, and role of this novel technique in the management of early-stage bca.

The effects of combined modality therapy on stage II-III primary gastric signet ring cell carcinoma.

e16530 Background: To date, there is no well-defined standard of care for gastric signet ring cell carcinoma (GSRC). Clinical guidelines support that combined modality therapy (CMT) on localized gastric cancer, but this may not be appropriate for GSRC as it was generally found to be chemo-resistant. We conducted a population-based study to examine the effects of therapeutic strategies on survival outcomes by using the Surveillance, Epidemiology, and End Results (SEER) data. Methods: Analyses included primary GSRC patients with stage II-III who survived more than 6 months, and were diagnosed between 2006 and 2016 from SEER data.CMT were categorized as gastrectomy group, adjuvant CT group (gastrectomy with adjuvant chemotherapy), neoadjuvant RT group (gastrectomy with neoadjuvant radiotherapy combined adjuvant chemotherapy), and adjuvant CRT group (gastrectomy with chemoradiotherapy). Survival analyses were conducted by Kaplan-Meier method and multivariate Cox proportional hazards models, adjusted for age, gender, race, marital status, histology, AJCC stage, tumor location, and lymph nodes removed. Models were stratified by gender, AJCC stage, lymph nodes removed and tumor location. Results: Of the 1,717 cases of stage II-III primary GSRC, the mean age was 66.9 (SD: 11.0) years, over a half were male (52.8%), and the majority were white (66.0%). A total of 39.9% received adjuvant CRT. The five-year overall survival (OS) rate was 34.6% for this treatment, and 29.6% for adjuvant CT group, 25.4% for adjuvant CRT group, only 23.8% for the gastrectomy group. The median OS of patients treated with adjuvant CRT was significantly longer than that of the gastrectomy group (33 vs 24 months, aHR = 0.71, 95%CI = 0.60,0.84). Although the crude model showed a significant association between adjuvant CT and total survival (cHR = 0.81, 95%CI = 0.68,0.96), the effect measure turned null in the multivariable and sub-group analysis. Independent prognostic factors were adjuvant CRT, ≥60 years old, AJCC stage, and &gt; 20 lymoh nodes removed. Conclusions: In this study, GSRC patients with stage II-III experienced improved overall survival after receiving adjuvant CRT, which provides several treatment implications. Future clinical trials considering adjuvant CRT will be needed to verify the conclusion derived from this study.