Local Recurrence-free Survival Research Articles

Pattern of Failure and Re-Irradiation for Stereotactic Radiotherapy Treated Brain Metastases from Non-Small Cell Lung Cancer (NSCLC)

Hypofractionated stereotactic radiotherapy (SRT) has been increasingly used for brain metastases (BMs) from non-small cell lung cancer (NSCLC). However, the prognostic factors, pattern of failure and clinical utility of re-irradiation for these patients remain have not been fully understood. Metastatic NSCLC patients receiving SRT that covering all of the intracranial tumor lesions and without prior whole brain radiotherapy (WBRT) were retrospectively enrolled. Local recurrence free survival (LRFS), intracranial progression free survival (iPFS) and overall survival (OS) were calculated from the initiation of SRT. Post intracranial progression survival (OS2) was measured from the initial intracranial disease progression. From 2018/05 to 2022/05, 218 patients were identified, with 142 (65.1%) having only one BM and 76 (34.9%) harboring 2-5 BMs. With a median follow-up of 31.1 (range, 1.0-44.6) months, median LRFS, iPFS and OS was 39.1, 26.6 and 31.1 months, respectively. No statistical difference of LRFS, iPFS and OS were found between patients with different numbers of BM. Nevertheless, patients receiving concurrent systemic therapy had significantly longer LRFS (HR = 0.35, p = 0.002), iPFS (HR = 0.57, p = 0.044) and OS (HR = 0.37, p = 0.001), when compared with those receiving SRT alone. By now, intracranial disease progression (iPD) was documented in 59 patients, with original site PD (OPD), new site PD (NPD) and both sites PD (BPD) occurring in 20 (33.9%), 17 (28.8%) and 22 (37.3%), respectively. Among the 59 patients, 19 (32.2%) received second-course SRT (re-SRT) targeting the intracranial progressive tumor lesions and re-SRT led to improved OS2 (22.7 vs 12.1 months, HR = 0.29, 95% CI 0.08-0.97, p = 0.045), which remained as an independent prognostic factor after multiple-variate Cox analyses. The status of systemic therapy, but not the number of BMs, may impact the survival outcomes of SRT-treated BMs from NSCLC. Some patients may benefit from re-SRT, which warranted future validation.

Dose Painting Radiotherapy Guided by Diffusion-Weighted Magnetic Resonance vs. 18F-FDG-PET/CT in Locoregionally Advanced Nasopharyngeal Carcinoma: A Randomized, Controlled Clinical Trial

This phase II randomized controlled trial aimed at comparing the efficacy and toxicity of diffusion-weighted magnetic resonance imaging (DWI)-guided dose painting radiotherapy (DP-RT), FDG-PET/CT-guided DP-RT, and conventional MRI-based radiotherapy (RT) in locoregionally advanced nasopharyngeal carcinoma (NPC). A total of 330 patients with stage III-IVa NPC disease were randomly assigned in a 1:1:1 ratio to receive induction chemotherapy followed by concurrent chemoradiotherapy by DWI-guided DP-RT (group A, n = 110), FDG-PET/CT-guided DP-RT (group B, n = 110), or conventional MRI-based RT (group C, n = 110). All patients received volumetric modulated arc therapy (VMAT). In group A, subvolume GTVnx-DWI (gross tumor volume of nasopharynx in DWI) was defined as the areas within the GTVnx (gross tumor volume of nasopharynx) with an apparent diffusion coefficient (ADC) below the mean ADC (ADC < mean). In group B, subvolume GTVnx-PET (gross tumor volume of nasopharynx in PET images) was defined within GTVnx as the SUV50%max isocontour. The doses to GTVnx-DWI in group A and GTVnx-PET in group B were escalated to 75.2 Gy/32 fx in patients with T1-2 disease and to 77.55 Gy/33 fx in those with T3-4 disease in 2.35 Gy per fraction. In group C, planning gross tumor volume of nasopharynx (PGTVnx) was irradiated at 70.4 to 72.6 Gy/32 to 33 fx in 2.2 Gy per fraction. This trial is registered with chictr.org.cn (ChiCTR2200057476). Group A and B showed significant higher complete response (CR) rates than group C (100%, 100%, and 96.4% for group A, B and C, respectively, p = 0.036). In groups A, B and C, the 1-year local recurrence-free survival (LRFS) rates were 100%, 100%, and 94.5%, respectively (p = 0.002). The 1-year disease-free survival (DFS) rates were 100%, 99.1%, and 92.7%, respectively (p = 0.001). The 1-year distant metastasis-free survival (DMFS) rates were 100%, 99.1%, and 93.6%, respectively (p = 0.004). The 1-year overall survival (OS) rates were 100%, 100%, and 95.4%, respectively (p = 0.006). Group A and B had significantly higher 1-year LRFS, DFS, DMFS, and OS than those in group C. No significant differences were observed in LRFS, DFS, DMFS and OS between group A and B. Group B (PET/CT group) had a higher incidence of grade 3-4 acute ototoxicity (3.6%) than group A (0%) and group C (0%, p = 0.036). No significant differences in other grade 3-4 acute adverse events and late toxic effects were observed among the three groups, and no patient had grade 5 toxicities. Multivariate analysis showed that dose painting (DWI-guided DP-RT and PET/CT-guided DP-RT vs conventional MRI-based RT) was associated with improved LRFS, DFS, DMFS and OS. Both DWI-guided DP-RT and PET/CT-guided DP-RT plus chemotherapy are associated with improved LRFS, DFS, DMFS and OS compared with conventional MRI-based RT among patients with locoregionally advanced NPC. DWI-guided DP-RT does not increase toxicities, but PET/CT-guided DP-RT has higher incidence of acute ototoxicity.

Outcomes of Consolidative Thoracic Radiation within First-Line Chemoimmunotherapy in Extensive-Stage Small-Cell Lung Cancer: Results from a Single Cancer Center

Thoracic radiation (TRT) benefits local control undoubtedly and survival with some minor controversy in extensive-stage small-cell lung cancer (ES-SCLC) patients undergoing radiotherapy in the chemoradiotherapy era. However, whether TRT could further enhance the benefit of immune checkpoint inhibitors (ICIs) maintenance on outcomes in the immunotherapy era is still unclear. This study aims to investigate the role of consolidative TRT in ES-SCLC patients receiving first-line chemoimmunotherapy followed by immunotherapy maintenance. Outcomes of patients who were treated with first-line chemo-immunotherapy followed by ICIs maintenance for ES-SCLC were reviewed. Based on TRT or not, patients were allocated to TRT group or non-TRT group. Progression-free survival (PFS), overall survival (OS) and local-recurrence free survival (LRFS) were calculated by the Kaplan-Meier method and compared by log-rank test. A total of 100 patients with no progressive disease after 4 cycles of chemotherapy were retrospectively analyzed between January 2020 and December 2021 and were allocated into TRT group (n = 47) and non-TRT group (n = 53). The median follow-up time was 20.3 months. The median PFS and OS in TRT were 9.1 months and 21.8 months, versus 8.8 months (p = 0.93) and 24.3 months (p = 0.63), respectively, in non-TRT. ICIs agents consisted of Durvalumab (59.0%) and Atezolizumab (41.0%). The median dose of TRT is 50 Gy (IQR: 45 - 54), while the median interval time from chemotherapy completion to TRT was 31 days (IQR: 12 - 44.5). Only 10 (21.3%) patients terminated ICIs in the period of TRT. The rate of intrathoracic progression after the first-line therapy in TRT significantly decreased compared to that with non-TRT (20.0% versus 55.9%, p = 0.003). The median LRFS time in TRT was not reached, but significantly longer than 10.8 months in non-TRT (HR = 0.27, p < 0.01). Second-line chemotherapy significantly prolonged survival compared to that with chemo-free patients (mOS: 24.5 vs. 21.4 months, p = 0.026). The subgroup analysis showed a trend of patients with brain metastases benefit from TRT (21.8 versus 13.7 months, HR 0.61, p = 0.38) while liver metastases did not (13.3 versus 15.0 months, HR 1.80, p = 0.21). Of 47 patients with TRT, only 10.6% of patients experienced grade 3 radiation-induced pneumonitis, while no grade 4 or 5 adverse events occurred. None of patients experienced grade ≥ 3 treatment-related cardiac events. Consolidative TRT in the period of immunotherapy maintenance followed first-line chemo-immunotherapy did not prolong OS and PFS but increased LRFS in ES-SCLC.

Survival Outcomes for Oligometastatic vs. Polymetastatic Extensive-Stage Small Cell Lung Cancer Following Consolidative Thoracic Radiotherapy

For patients with limited metastatic burden, metastasis-directed radiotherapy has been shown to be associated with improved OS for certain types of cancer. However, these prior trials did not include patients with ES-SCLC. It is not yet clear if patients with oligometastatic ES-SCLC have improved outcomes over polymetastatic ES-SCLC after cTRT. We identified patients treated with cTRT for ES-SCLC in 2013-2020 at a single institution. Oligometastatic disease was defined at the time of diagnosis as three or fewer organs with distant disease, and with each organ having three or fewer metastatic lesions. All other patients were considered polymetastatic. The Kaplan-Meier estimator, log-rank test, and multivariable Cox proportional hazards regression were used to compare OS, progression-free survival (PFS), local recurrence-free survival (LRFS), and new metastasis-free survival (NMFS) between oligometastatic and polymetastatic ES-SCLC patients undergoing cTRT. Among 70 included patients, 36 were defined as oligometastatic. All patients received platinum-doublet chemotherapy and cT. Immunotherapy was given in 7 (19.4%) oligometastatic patients and 5 (14.7%) polymetastatic patients (p = 0.56). Median follow-up time was 38.2 months. Multivariable Cox regression analysis showed that oligometastatic disease (vs. polymetastatic disease) at diagnosis was associated with improved OS (hazard ratio [HR] 0.44, 95% CI 0.25-0.78, p = 0.005, 1-year OS 86.1% vs. 46.9%, 2-year OS 47.1% vs. 15.1%). PFS, LRFS, and NMFS were not significantly different between the cohorts. Among oligometastatic patients, pleural involvement (HR 2.44, 95% CI 1.02-5.83, p = 0.046) and lung involvement (HR 4.93, 95% CI 1.02-23.9, p = 0.047) were associated with inferior OS. Among the 26 of 36 (72.2%) oligometastatic patients with neither pleural nor bilateral lung involvement, 1-year OS was 88.5% and 2-year OS was 58.3%. We observed that oligometastatic ES-SCLC patients treated with cTRT (especially those without pleural or bilateral lung involvement) have superior OS than those with polymetastatic disease. We encourage enrollment on the NRG LU007/RAPTOR randomized trial to determine the impact of complete or incomplete consolidative RT to up to 5 sites in ES-SCLC, especially in those with oligometastatic disease.

Eosinophil Dynamics during Chemo-Radiation Correlate to Clinical Outcome in Stage II-IVA Nasopharyngeal Carcinoma Patients: Results from a Large Cohort Study

We investigated the dynamics of eosinophil depletion and recovery during definitive concurrent chemo-radiotherapy (CCRT) and how they affect the prognosis of stage II-IVA nasopharyngeal carcinoma (NPC) patients. A total of 1225 patients with pathologically proven NPC from 2013 to 2019 were enrolled. Fuzzy C-Means Clustering (FCM) was used to assess trends in eosinophil during CCRT longitudinally and to grade eosinophil decline during treatment in combination with absolute eosinophil counts (AECs) at the end of CCRT. Grade G0 refers to patients with no decreasing trend in eosinophils and AECs >0.05×109 cells/L, grade G1 refers to patients with a decreasing trend in eosinophils or AECs between 0-0.05×109 cells/L, grade G2 refers to patients with a decreasing trend in eosinophils and AECs between 0-0.05×109 cells/L. Progression-free survival (PFS) is the primary outcome measure, with overall survival (OS), distant metastasis-free survival (DMFS), and local recurrence-free survival (LRFS) as secondary outcome measures. A Cox proportional risk model was used to determine the hazard ratio for adverse prognostic effects in declining grades of eosinophil. During a median follow-up of 4.1 years, 376 (30.69%) patients experienced disease progression events. The grade of eosinophil reduction after CCRT was significantly associated with PFS, OS, and DMFS but not with LRFS. After adjusting for demographics, clinical baseline indicators, tumor characteristics, and treatment characteristics, a 1.57-fold (p = 0.001), 1.69-fold (p = 0.007), and 1.51-fold (p = 0.019) increase in the risk of developing PFS, OS, and DMFS was observed for G1 compared with G0, whereas a 2.4-fold (p < 0.001), 2.76-fold (p < 0.001), and 2.31-fold (p < 0.001) increase in the risk of developing PFS, OS, and DMFS was observed for G2. Moreover, among patients with G0, treatment with CCRT with a cumulative dose of platinum-based chemotherapy < 200 mg/m2 resulted in PFS, OS, and DMFS that were not inferior to CCRT with cumulative doses ≥ 200 mg/m2. Eosinophil is an easily detectable and inexpensive biomarker that may be useful in the clinical setting to aid in assessing the prognosis for standard treatment of NPC.

Standard Therapy vs. Individualized Therapy in Elderly Locally Advanced Nasopharyngeal Carcinoma: A Real-World Study

Concurrent chemoradiotherapy (CRT) with/without induction chemotherapy has been the standard therapy (ST) for locally advanced nasopharyngeal carcinoma (LA-NPC). However, most patients supporting these clinical trials were younger than 65 years of age. For the toxicity of CRT and the poor tolerance of elderly patients, it is still controversial whether ST could bring the most promising survival benefits for elderly NPC compared with individualized therapy (IT). Thus, in this real-world study we compared the survival and safety of ST with IT in elderly LA-NPC to explore an effective and tolerable treatment strategy for elderly LA-NPC. A total of 109 newly diagnosed elderly LA-NPC (>65 years old) from Jan. 2013-Jul. 2020 were retrospectively enrolled and divided into the ST group and IT group according to the original treatment tendency. ST refers to CRT with/without induction chemotherapy. IT group included patients not suitable for CRT and were given individualized treatment fully discussed by at least two oncologists from our head and neck team. A 1:1 propensity score matching (PSM) generated a matched cohort of ST and IT. The survivals and treatment related toxicities were compared between the two groups. There were 46 cases in the ST group and 63 cases in the IT group. The 5-year overall survival (OS) rate, cancer-specific survival (CSS) rate, progression- free survival (PFS) rate, local recurrence-free survival (LRFS) rate and distant metastasis-free survival (DMFS) rate were 68.64%, 76.42%, 73.69%, 85.67% and 86.82%, respectively. By 1:1PSM, 35 cases in each group were matched. No significant differences of OS, CSS, PFS, LRFS and DMFS were found between ST and IT groups in the PSM-matched cohorts (P = 0.87, P = 0.79, P = 0.51, P = 0.81 and P = 0.24, respectively). Compared with patients in the ST group, cases received IT were associated with less severe acute toxicities including anemia, leucopenia, neutropenia, and thrombocytopenia. For elderly LA-NPC, IT had similar survivals while less severe toxicities compared with ST, which revolutionarily challenged the role of ST for elderly LA-NPC. In the future, more studies are need to explore a less toxic treatment modality with noninferior efficacy for elderly LA-NPC.

Different Radiation Dose of Neoadjuvant Chemoradiation for Resectable Thoracic Esophageal Squamous Carcinoma: A Randomized Phase II Clinical Trial

Radiation dose used in the neoadjuvant chemoradiotherapy (nCRT) for patients with locally advanced esophageal squamous cell carcinoma (ESCC) varies in clinical practice, no prospective studies have been conducted on this issue. The hypothesis of this study is that higher radiation dose in nCRT was associated with improved progression free survival in resectable ESCC. A phase II prospective randomized controlled trial was conducted from February 22, 2018 to February 22, 2021 in Zhejiang Cancer Hospital (NCT03381651). Patient with locally resectable advanced thoracic ESCC (cT2-T4aNxM0, T1-3N+M0) were randomized 1:1 to receive nCRT with different radiation doses of 50.4 Gy/28F and 41.4 Gy/23F, weekly TC regimen (paclitaxel 50 mg/m2, d1, carboplatin AUC = 2, d1) was administered as concurrent chemotherapy. The primary endpoint was 2-year progression free survival (PFS), and the secondary endpoints included complete pathological response (pCR) rate, overall survival (OS), local recurrence free survival (LRFS), and distant metastasis free survival (DMFS). The last follow-up date was February 22, 2022 and data analysis was performed from May 1, 2022, to October 31, 2022. A total of 147 patients were enrolled in the prospective study, including 72 patients in 50.4 Gy/28F group and 75 patients in 41.4 Gy/23F group. Among all the patients, 101 patients finally underwent surgical resection, 23/46(50%) achieved pCR in the high-dose group, while 18/55(32.7%) achieved pCR in the low-dose group (P = 0.10). In intention-to-treat population analysis, 2-year PFS in the high-dose and low-dose groups were 53.5% (95% CI: 42.9-66.7%) and 45.5% (95% CI: 35.4%-58.5%), respectively, and hazard ratio (HR) was 0.72 (95% CI: 0.46-1.12, P = 0.14). Median PFS were 44.4 months (95% CI: 16-NA) versus 20.8 months (95% CI: 15-NA) in high and low dose groups. 2-year OS in the high and low-dose groups were 61.8% (95% CI: 51.2 -74.5%) and 60.5% (95% CI: 50.3 -72.8%), respectively, with a HR = 0.78(95% CI: 0.48-1.27, P = 0.32). Median OS were not arrived in both groups up to the last follow-up. In addition, 2-year LRFS were 87.9% (95% CI: 78.4-98.5%) and 74.8% (95% CI: 63.3-88.3%) in high and low-dose groups, while 2-year DMFS were 70.6% (95% CI: 58.3-85.5%) and 73.6% (95% CI: 61.7-87.8%), respectively. No significant statistical difference was observed between the two groups in terms of side effects during nCRT and postoperative complications. Our results showed that neoadjuvant high-dose radiotherapy failed to improve overall survival in ESCC. However, it was found that pCR and local tumor control rates tended to be increased at 50.4 Gy/28F, compared to 41.4 Gy/23F, although the trend was not statistically significant. There was no significant difference in treatment side effects between the two groups. Longer-term follow-up is required to verify our findings.

Postoperative Radiotherapy to Abdominal and Pelvic Lymphatic Drainage Area for Stage III Epithelial Ovarian Cancer: A Sharp Tool to Prolong Disease-Free Survival Time

For patients with stage III epithelial ovarian cancer, there are limited studies on the effects of postoperative adjuvant radiotherapy (RT) after standard cytoreductive surgery (CRS) and full treatment of first-line adjuvant chemotherapy (CT). The aims of our study were to assess the therapeutic efficacy and toxicity of our special postoperative radiotherapy to abdominal and pelvic lymphatic drainage area for stage III epithelial ovarian cancer patients. We retrospectively collected patients with stage III epithelial ovarian cancer after CRS and full-course adjuvant chemotherapy. The CT+RT group patients were treated with intensity modulated radiotherapy (IMRT) to abdominal and pelvic lymphatic drainage area (which has been shown to be an alternative to whole abdominal radiotherapy (WART) both on the basis of clinical result and dosimetric verification from our prior study). The CT group data was obtained from the PUMCH's electronic medical record analytical database between 2010 and 2020. A propensity score matching analysis was performed 1:2 between CT+RT group and CT group. A total of 132 patients with median follow-up of 73.9 months (9.1-137.7 months) were included (44 and 88 for the CT+RT and CT groups, retrospectively). The baseline characteristics of age, histology, level of CA12-5, surgical staging, residual tumor, courses of adjuvant CT, and courses to reduce CA12-5 to normal were all balanced. The median disease-free survival (DFS) time, 5-year overall survival (OS), and local recurrence free survival (LRFS) of CT+RT group and CT group were 100.0 months versus 25.9 months (p = 0.020), 69.2% versus 49.9% (p = 0.002), 85.9% versus 50.5% (p = 0.020), respectively. Distant metastasis was still the primary reason (57.6%), and local failure rate was 42.3%, the local recurrence rate was significantly lower in CT+RT group, compared with CT group (13.6% versus 45.5%, p = 0.016). In terms of toxicity, CT+RT group mainly presented with acute hematological toxicities, with no statistically significant difference with CT group when compared with grade III intestinal adverse effects (3/44 versus 6/88, p = 0.480). This report demonstrates that long-term disease-free survival could be achieved in stage III epithelial ovarian cancer patients treated with IMRT preventive radiation to abdominal and pelvic lymphatic area. Compared with CT group, DFS and OS were significantly prolonged and adverse effects were acceptable.

Interim Analysis of a Non-Randomized Prospective Trial Comparing Hypofractionated Post-Mastectomy Radiotherapy (HF-PMRT) to Conventional Post-Mastectomy Radiotherapy (CF-PMRT) for Breast Cancer (BC) Patients

The standard of care for treatment for LABC patients who have undergone modified radical mastectomy (MRM) is PMRT. Post-mastectomy RT (PMRT) for LABC patients has been established in three trials to improve locoregional control and overall survival (OS). A published trial from China showed that HF-PMRT was non-inferior to CF-PMRT. This study was conducted to determine if HF-PMRT can provide similar efficacy and toxicity. A non-randomized prospective trial design was employed to compare HF-PMRT and CF-PMRT in post-MRM BC patients. Patients with pathologically proven BC who underwent MRM without positive margins and with less than 8 positive nodes were included. Informed consent was obtained. Patients decided which treatment they will receive. They received either HF-PMRT of 43.2 Gy in 16 fractions (fx) [2.7 Gy/fx] or CF-PMRT of 50-50.4 Gy in 1.8-2.0 Gy/fx to both chest wall and regional nodes (axillary and supraclavicular) in both regimens. Primary endpoints were 2-year OS and 2-year local recurrence free survival (LRFS). Secondary endpoints include acute and late toxicities. Analysis was done as intention-to treat. An interim analysis of 2-year results is presented. A total of 37 patients were enrolled in two separate cohorts: a single-arm cohort that recruited 10 HF-PMRT patients from 2014-2015 and a two-arm prospective trial that started recruitment last 2019 and included 12 HF-PMRT and 15 CF-PMRT patients. Median follow-up was 35 months. There were more Stage IIB and Stage III for the CF-PMRT arm [p = 0.040]. Treatment interruptions were more frequent in the CF-PMRT arm (100% vs 68%, p = 0.028). The duration of interruption was also longer in CF-PMRT (median 8 vs 3 days) [p < 0.003]. Acute and late toxicities were not statistically different. There was one patient each with RTOG Grade 2 acute skin toxicity in the HF-PMRT (4.55%) and CF-PMRT arms (6.67%) [p = 0.703]. For late toxicities, the HF-PMRT arm had 6 Grade 1 late skin toxicities and 1 Grade 3 late skin toxicity vs 1 Grade 1 late skin toxicity for CF-PMRT arm [p = 0.196]. 2-year OS rate (86.3% vs 100%, p = 0.403) 2-year DFS rate (68.18% and 73.33%, p = 0.126) were both not statistically different. There were no reported locoregional recurrences (LCR). In terms of local control, both arms have showed no LCRs. 2-year OS and DFS rate were no different. As the study has not yet reached the adequate sample size, the non-inferiority of HF-PMRT cannot be definitively concluded. Acute and late toxicities were no different. There was a significantly higher rate of treatment interruptions in the CF-PMRT compared to the HF-PMRT arm. The results of this interim analysis prove to be promising and patients will continue to be accrued. The final results of this study might have tremendous implications in local practice.

Outcomes and after Hyperfractionated, Accelerated Reirradiation for Recurrent Anal Squamous Cell Carcinoma

Abdominoperineal resection (APR) is the standard salvage treatment for recurrent or persistent squamous cell carcinoma of the anus (SCCA). However, reirradiation (reRT) can be used preoperatively or for those who are not candidates for surgery. Using a single institutional database, patients were identified who underwent reRT for SCCA from 2003 to 2022. Response to reRT and outcomes after reRT were recorded. Variables analyzed included age at reRT, sex, reason for reRT (recurrent SCCA vs new SCCA after pelvic radiation for a different malignancy), interval between initial radiation and reRT, reRT dose, concurrent chemotherapy, receipt of APR and the presence of distant metastases at the time of reRT. Cox Proportional Hazard Model was used; multivariable analysis for all factors with a univariate P-value <0.1 on univariable analysis. A total of 42 patients received reRT, which consisted of 1.5 Gray (Gy) twice daily fractions with ≥6-hour interval to a total dose ranging 30Gy to 54Gy (median [IQR] 39Gy [39-42Gy]. Thirty-eight patients (90.5%) received concurrent chemotherapy; most often with weekly cisplatin and 5-fluorouracil (N = 23, 54.8%). Median [IQR] follow-up after reRT was 11.4 months [4.9-40.8 months]. Median [IQR] initial radiation dose was 54Gy [54-58Gy], and median [IQR] interval between initial radiation and reRT was 3.6 years [2.1-6.0 years]. For 8 patients (19.1%), the initial radiation was given for a different pelvic malignancy prior to being diagnosed with SCCA. Four of these patients received brachytherapy alone or in conjunction with external beam. For the remaining 34 patients, the initial radiation was for SCCA and the reRT was for recurrent SCCA either in the anal canal (N = 23, 67.6%) or regional nodes (N = 11, 32.3%). Four patients (9.5%) had distant disease at the time of reRT. Eleven patients (26.2%) had planned APR after preoperative reRT; 1 patient had a pathologic complete response (pCR), 2 patients had a near pCR (<5% viable cancer). Twenty-nine patients (69.0%) were treated with reRT alone; 15 (51.7%) attained a clinical CR. Two patients (4.8%) were treated with palliative intent and response was not assessed. Median local recurrence free survival (LRFS) was 9.9 months; 2- and 3-year LRFS were both 41%. Median distant metastasis free survival (DMFS) was 11.8 months; 2- and 3-year DMFS were 38% and 34%, respectively. Median overall survival (OS) was 40.5 months; 2- and 3-year OS were 54% and 51%, respectively. On multivariable analysis, only the presence of distant disease at the time of reRT was significantly associated with worse LRFS (HR (95% CI) 4.14 (1.34-12.81); P = .014), worse DMFS (4.06 (1.37-12.06); P = .012) and worse OS (5.73 (1.57-20.9); P = .008). ReRT is an option for patients presenting with either recurrent SCCA or new SCCA after prior pelvic radiation for a different malignancy. ReRT can be given prior to planned salvage APR or alone for patients who are not surgical candidates with an approximate 50% cCR rate.

Toxicity and Efficacy of Hypofractionated Regional Nodal Irradiation

Hypofractionated whole-breast irradiation (HF-WBI) has been widely adopted. However, there are still limited data on whether hypofractionated regional nodal irradiation (HF-RNI) is safe and effective. We report toxicity and cancer outcomes with our HF-RNI approach. This retrospective study included 154 patients with node-positive or high-risk node-negative breast cancer treated with HF-RNI with curative intent at a single academic institution from 2008-2020. Median dose to the breast or chest wall/reconstructed breast was 40 Gy in 16 fractions (interquartile range [IQR], 40-45 Gy in 16-18 fractions). Median dose to the regional nodes was 40 Gy in 16 fractions (IQR, 40-40 Gy in 16-16 fractions). The primary end-point was the rate of chronic toxicity. Secondary endpoints were local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS), disease-free survival (DFS), and overall survival (OS). Toxicities were scored using the Common Terminology Criteria for Adverse Events v5.0 and Radiation Therapy Oncology Group scale where appropriate. This study was approved by the Institutional Review Board. Median follow-up was 46 months (IQR 33-63 mo). Median age at diagnosis was 58 years. Sentinel lymph node biopsy (SLNB) was performed in 49% of patients, 16% underwent both SLNB and axillary lymph node dissection (ALND), 32% underwent ALND alone, and 3% had no axillary surgery; 79% had partial mastectomy and 21% had total mastectomy with or without reconstruction. The nodal target included the supraclavicular and axillary Level 1-3 nodes in 66% of patients and supraclavicular and Level 3 nodes in 34%. The crude incidence of grade 1 chronic brachial plexopathy was 2%, grade 1 chronic limited range of motion (LROM) of the upper extremity was 3%, and chronic upper extremity lymphedema was 8% (11 patients with grade 1 toxicity and 1 patient with grade 2 toxicity). The only grade 3+ chronic toxicity was hyperpigmentation (1%). The median time to the development of the highest-grade toxicity was 10 months for brachial plexopathy, 10 months for LROM, and 11 months for lymphedema, respectively. Five-year actuarial rates of LRFS, RRFS, DFS, and OS were 98%, 99%, 90%, and 88%, respectively. HF-RNI resulted in low rates of chronic toxicities and excellent disease control in this study. Results of randomized trials of HF-RNI are needed for definitive evidence, but these retrospective data support wider adoption of HF-RNI.

Stereotactic Body Radiation Therapy (SBRT) for Head and Neck Cancer Re-Irradiation: Should >180˚ Carotid Encasement or Dermal Involvement Remain an Exclusion Criteria?

Patients with recurrent head and neck cancer (HNC) who present with carotid encasement (CE) >180˚ and skin involvement/abutment (SI/A) are often not considered for SBRT re-irradiation and are excluded from RTOG 3507. We reviewed our institutional experience of SBRT re-irradiation in such cases. From an IRB approved registry, we identified previously irradiated HNC patients treated by SBRT with CE >180˚, SI/A, or use of bolus from 2013-2022. Toxicity as per CTCAEv4.0 and recurrence patterns were analyzed. The cumulative incidence of local progression was estimated with death as a competing risk. Survival analysis was performed with the Kaplan-Meier method. Thirty-five patients were treated with SBRT to 37 sites with median follow up of 5.7 months (mo) (IQR 2.7-10.6). A total of 20 cases exhibited CE >180˚, 20 cases had SI/A, and 3 cases had both. The median time from prior radiation was 12.7 mo (range 1.9-144.1). Histology was squamous cell carcinoma in 89%. The site of SBRT was most commonly the neck (65%), 24% mucosa, 8% skull base, and 3% scalp. SBRT was delivered in 5 fractions every other day (62%) or 2 fractions per week (38%). 78% (N = 29) received ≥40 Gy while 22% (N = 8) received a lower dose. The cumulative incidence of local failure at 3 and 6 mo was 12.4% (95% CI 0.8-24.0) and 31.3% (95% CI 14.9-47.8), respectively. The median time of local and regional recurrence free survival was 7.0 and 4.9 mo. Median OS was 8.3 mo. Of the 20 cases with true SI, 40% (N = 8) completely resolved, 35% (N = 7) improved or had residual ulceration attributed to disease, and 25% (N = 5) had ulceration related to toxicity. There were no carotid bleeding events (CBE) related to SBRT, however 10% (N = 2) experienced fatal CBE related to progressive disease at 2.3 mo and 6.7 mo from SBRT. The rate of grade ≥2 treatment related skin toxicity was 19% (N = 7) and only occurred in those with pre-SBRT SI/A. These included a grade 2 neck wound and tracheostomy infection, a grade 3 infection, and two grade 3 soft tissue necrosis. One patient had cellulitis/meningitis related to scalp radiation, and one had an untreated SBRT wound as they transitioned to hospice. Dysphagia requiring PEG occurred in 5% (N = 2), one of which was related to CNX palsy. Six patients (17%) had post-SBRT nerve impairment including one each of grade 2 facial nerve paralysis, grade 2 brachial plexopathy, grade 3 CNVIII dysfunction, grade 3 CNX impairment, and two patients with grade 2 CNXII impairment. SBRT for locally recurrent previously radiated HNC can provide effective local control in a patient population at high risk of morbidity and mortality from local disease progression. In patients who have >180˚ CE or SI/A, we observed non-trivial toxicity, but disease progression may have been more morbid. For appropriately counseled patients with limited treatment options, CE or SI/A may not be an absolute contraindication to SBRT re-irradiation.

Definitive Chemoradiation with Concurrent Carboplatin and Paclitaxel for HPV-Mediated Oropharyngeal Cancer (p16+ OPSCC): Survival and Local Control

Standard therapy for locally advanced p16+ OPSCC with cisplatin and bilateral nodal RT results in substantial acute and late toxicities. De-intensification strategies are under active investigation, including the de-escalation of RT dose and field size and use of less toxic RT sensitizing agents. We present our single-institution experience with definitive chemoRT using weekly carboplatin and paclitaxel and modified RT. A retrospective review of 139 consecutive patients with non-metastatic p16+ OPSCC treated with definitive chemoRT from 2013 to 2019 was performed. IMRT dose ranged from 60 to 70 Gy (median 69.96 Gy) to gross disease and 44 to 59.4 Gy (median 54.45 Gy) to elective nodal sites. Modified RT included dose reduction from 70 Gy EQD2 to 60-67.8 Gy EQD2 (2.0-2.2 Gy/fraction) and/or field modified contralateral neck. All patients received concurrent weekly paclitaxel (30 mg/m2) and carboplatin (AUC 1); 34 (24.5%) received induction chemotherapy. Patients were classified as low or intermediate risk based on HPV status, smoking history, and nodal staging per RTOG 0129 risk stratification. OS, local and regional RFS, and DSS were estimated using Kaplan-Meier method. Median FU was 40.5 months. Of 139 pts, 96 were low and 43 were intermediate risk. Median age 61 yrs (range, 40-81 yrs). 125 pts were male and 14 were female. TNM staging: 29 pts (20.9%) were T1 (22 N1, 7 N2), 68 (48.9%) T2 (4 N0, 52 N1, 12 N2), 27 (19.4%) T3 (5 N0, 15 N1, 7 N2), and 15 (10.8%) T4 (2 N0, 2 N1, 10 N2, 1 N3). Median smoking history of 22.5 pack-yrs (range, 0.25-150 pack-yrs); 59 never smoked. LR recurrence was noted in 6/96 (6.3%) low risk and 7/43 (16.3%) intermediate risk pts. DM developed in 11/96 (11.5%) low risk and 8/43 (18.6%) intermediate risk pts. Synchronous LR recurrence and DM were noted in 1/96 (1%) low risk and 2/43 (4.7%) intermediate risk pts. The 3-year LRC was 93.6% (95% CI, 86.3-97.1) in the low-risk and 77.8% (95% CI, 61.4-87.8) in the intermediate-risk group. The 3-year OS was 95.4% (95% CI, 88.3-98.3) in the low-risk and 77.6% (95% CI, 61.3 to 87.7) in the intermediate-risk group. The 3-year DSS was 96.6% (95% CI, 89.7-98.9) in the low-risk and 86.8% (95% CI, 71.0-94.3) in the intermediate-risk group. Definitive chemoRT for p16+ OPSCC with concurrent carboplatin and paclitaxel and a modified RT regimen designed to minimize acute and late effects of therapy demonstrated comparable outcomes to standard cisplatin-based chemoRT, such as report on RTOG 0129, with a high rate of LRC at 3 years. Our analysis suggests a role for a less intensive regimen using paclitaxel and carboplatin as a less toxic, effective alternative to cisplatin in the curative management of p16+ OPSCC, particularly in low-risk patients. Strategies for combating distant metastases are needed. Toxicity analysis planned to be presented separately.

Low-Dose Fractionated Radiotherapy Combined with Neoadjuvant Chemotherapy for T3-4 Nasopharyngeal Carcinoma Patients: The Preliminary Results of a Phase II Randomized Controlled Trial

Over 70% of NPC patients were local advanced NPC (LANPC). The 5-year local recurrence-free survival rate is only 70% in T3-4 patients. Neoadjuvant chemotherapy (NACT) followed with concurrent chemoradiotherapy (CCRT) was recommended for LANPC patients. Low-dose fractionated radiotherapy (LDFRT), which is <100cGy, induces enhanced cell killing by the hyper-radiation sensitivity phenomenon and potentiates effects of chemotherapy. The synergy of LDFRT and NACT has not been used in the clinical practice and few studies focused on it. A single arm study found the ORR of primary site was improved to 90% for head and neck squamous carcinoma patients treated with LDFRT and NACT. Our previous study found the ORR of lymph nodes was higher in LDFRT group for high-risk LANPC patients. However, another study showed there was no significant difference between LDFRT and control group for LANPC patients. So, we aimed to investigate the potential efficacy of this novel neoadjuvant therapy for T3-4 NPC patients. A total of 60 pathological confirmed T3-4 (UICC/AJCC8th) NPC patients were prospectively enrolled in our study. They were randomly assigned to two groups. For the LDFRT group, the patients received 3 cycles of NACT (docetaxel 75mg/m2 D1, cisplatin 80mg/m2 D1) with LDFRT, and followed with CCRT. LDFRT was delivered as 50cGy per fraction twice a day to primary site on D1,2 for each cycle of NACT. The patients in the control group only received NACT and followed with CCRT. All the patients underwent IGRT. RECIST criteria and CTCAE 5.0 was used to evaluate the ORR and toxicity at post-NACT and the completion of CCRT. From February 2022 to December 2022, 60 T3-4 NPC patients were included, and 30 patients for each group. For the primary site, the median volume reduction rate and the ORR after NACT was significantly improved in LDFRT group (69.27% vs 40.10%, p<0.001;93.33% vs 73.33%, p = 0.038). For the median volume reduction rate of primary site and lymph node, it was also obviously improved in LDFRT group (86.59% vs 55.43%, p<0.001). Though there was a tendency of ORR improvement in LDFRT group, but no significant difference (96.67% vs 83.33%, p = 0.195). After the completion of CCRT, the median volume reduction rate of primary site had an increased tendency in LDFRT group (96.16% vs 88.3%, p = 0.065), but the ORR had no statistical significance (LDFRT group: CR 45.8%, PR 54.2%; control group: CR 37.5%, PR 62.5%). For the toxicity, the incidence of grade 3-4 adverse events had no difference between two groups (p = 0.786). No grade 5 adverse events occurred. LDFRT combined with NACT could obviously improve the median volume reduction rate and ORR of primary tumor for T3-4 NPC patients, and the toxicity was similar and tolerable. This novel treatment could be a promising strategy to improve treatment response and needed to be confirmed further.

Post-Chemoradiation Metastatic, Persistent and Resistant Nodes in Locally Advanced Rectal Cancer: Metrics and Their Impact on Long-Term Outcome.

The purpose of this study was to evaluate the long-term oncological progression pattern of locally advanced rectal cancer patients with post-neoadjuvant nodal metastatic disease (ypN+) and correlate potential prognostic features associated with proven radiochemoresistant nodal biology. Individual patient data (100 variables) from a 20-year consecutive single-institution multidisciplinary experience (1995-2015), delivering multimodal therapy to rectal cancer patient candidates for radical treatment, including a neoadjuvant component and surgical resection with or without intraoperative radiotherapy followed by optional adjuvant chemotherapy. The ypN+ disease data was registered in the context of initial staging categories post-neoadjuvant T status (ypT). Data on 487 patients showed histologically confirmed diagnoses of metastatic nodal disease in 108 specimens (ypN+, 22.1). There was a significant age difference (p = 0.009) between the ypN groups: age ≥ 65 was 57.6% in pN0 and 43.5% in ypN+ and patients aged < 65 constituted 42.4% of pN0 and 56.5% of ypN+. According to the clinical stage there were statistically significant differences (p = 0.001) in the categories' distribution: ypN+ patients 10.8% were stage II and 89.2% were stage III. Univariant analysis on outcome variables showed statistically significant differences in overall survival at 7 years (63.8% vs. 55.7%, p = 0.016) disease-free survival (DFS) (78% vs. 53.8%, p = 0.000) and local recurrence-free survival (LRFS) (93.6% vs. 84%, p = 0.002). The presence of nodal metastases (ypN+) after neoadjuvant therapy containing long-course pelvic irradiation severely impacts the long-term outcome for patients with locally advanced rectal cancer and correlates with multiple clinical and therapeutic variable metrics. Implementation of local and systemic therapies should be adapted and intensified in relation to the finding of ypN+ category in surgical specimens.

Matted Lymph Nodes on MRI in Nasopharyngeal Carcinoma: Prognostic Factor and Potential Indication for Induction Chemotherapy Benefits.

Lymph node characteristics markedly affect nasopharyngeal carcinoma (NPC) prognosis. Matted node (MN), an important characteristic for lymph node, lacks explored MRI-based prognostic implications. Investigate MRI-determined MNs' prognostic value in NPC, including 5-year overall survival (OS), distant metastasis-free survival (DMFS), local recurrence-free survival (LRFS), progression-free survival (PFS), and its role in induction chemotherapy (IC). Retrospective cohort survival study. Seven hundred ninety-two patients with non-metastatic NPC (female: 27.3%, >45-year old: 50.1%) confirmed by biopsy. 5-T/3.0-T, T1-, T2- and post-contrast T1-weighted fast spin echo sequences acquired. MNs were defined as ≥3 nodes abutting with intervening fat plane replaced by extracapsular nodal spread (ENS). Patients were observed every 3 months for 2 years and every 6 months for 5 years using MRI. Follow-up extended from treatment initiation to death or final follow-up. MNs were evaluated by three radiologists with inter-reader reliability calculated. A 1:1 matched-pair method compared survival differences between MN-positive patients with or without IC. Primary endpoints (OS, DMFS, LRFS, PFS) were calculated from therapy initiation to respective event. Kappa values assessed inter-reader reliability. Correlation between MN, ENS, and LNN was studied through Spearman's correlation coefficient. Clinical characteristics were calculated via Fisher's exact, Chi-squared, and Student's t-test. Kaplan-Meier curves and log-rank tests analyzed all time-to-event data. Confounding factors were included in Multivariable Cox proportional hazard models to identify independent prognostic factors. P-values <0.05 were considered statistically significant. MNs incidence was 24.6%. MNs independently associated with decreased 5-year OS, DMFS, and PFS; not LRFS (P = 0.252). MN-positive patients gained significant survival benefit from IC in 5-year OS (88.4% vs. 66.0%) and PFS (76.4% vs. 53.5%), but not DMFS (83.1% vs. 69.9%, P = 0.145) or LRFS (89.9% vs. 77.8%, P = 0.140). MNs may independently stratify NPC risk and offer survival benefit from IC. 3 TECHNICAL EFFICACY: Stage 2.

Lateral lymph node involvement presents another challenge in rectum cancer in the age of neoadjuvant chemoradiotherapy + total mesorectal excision: an evaluation of survival outcomes.

In the last decades, total mesorectal excision (TME) and neoadjuvant chemoradiotherapy (nCRT) have produced an undeniable improvement in the treatment of rectal cancer. However, local recurrence is still an important problem, and the effect of lateral lymph node (LLN) involvement on local recurrence is a controversial issue. The aim of this study was to investigate the effects of LLN status on local recurrence and survival in rectal cancers treated with nCRT + TME. Clinical features, pre- and post-nCRT lateral pelvic region imaging, long-term local recurrence, and the survival outcomes of 114 patients who underwent nCRT + TME for rectal cancer were evaluated. On MRI before nCRT, 20 (17.5%) patients had lateral lymph nodes (LLN+), and 94 (82.5%) patients had no lymph nodes in the lateral pelvic compartments (LLN-). Local recurrences at 1 year in LLN+ and LLN- patients were 3 (15.8%) and 2 (2.3%), respectively (p=0.039). Five-year local recurrence-free survival rates and the mean duration of recurrence-free survival in LLN+ and LLN- patients were 56.2%, 42.6 months, and 87.3% 66.9 months, respectively (p=0.001). Disease-free survival and overall survival were shorter in LLN+ patients, but the difference was not statistically significant (p=0.096 and p=0.46, respectively). In the multivariate analysis, LLN involvement was determined to be an independent risk factor for local recurrence-free survival (Hazard Ratio 4.54, p=0.003). Lateral lymph node involvement causes local recurrence to remain high after nCRT + TME. LLN status should be considered in treatment planning. Further studies are needed to define precise criteria for LLN involvement and the effect of LLND on local recurrence and survival.

Local anaesthesia vs. general anaesthesia for percutaneous microwave ablation in hepatocellular carcinoma: efficacy, safety, and cost analysis.

To compare the efficacy, safety, and cost of local anaesthesia and general anaesthesia modalities for percutaneous microwave ablation as a curative treatment for hepatocellular carcinoma patients. This comparative, retrospective study analysed 175 patients who were treated for hepatocellular carcinoma (HCC) from July 2015 to September 2020. Conventional transcatheter arterial chemoembolization (cTACE) combined with sequential percutaneous microwave ablation (MWA) was performed on every lesion in every patient. Patients were divided into two cohorts according to the anaesthesia modality applied during MWA. To investigate the differences in efficacy between the two groups, overall survival (OS) and local recurrence-free survival (LRFS) were estimated by the Kaplan-Meier method and compared by the log-rank test. Cost and safety between the two groups were also compared accordingly. There were 105 patients with 128 HCC lesions in the local anaesthesia (LA) group and 70 patients with 107 lesions in the general anaesthesia (GA) group. There were no significant differences in OS (P = 0.798) or LRFS (P = 0.406) between the two groups. Fifty-two pairs of patients were matched with 77 lesions in the GA group and 67 lesions in the LA group after PSM. There was no significant difference in OS (P = 0.522) or LRFS (P = 0.410) between the two groups. Compared to the LA group, the GA group had longer operations, consumed more medical resources, had a heavier financial burden, and experienced more anaesthesia adverse events. There was no significant difference in the incidence of post-ablation pain (p=0.487), fever (P=0.678), nausea or vomiting (P=0.808), mild liver dysfunction (P=0.753), haemolytic uraemic syndrome (P=0.595), pleural effusion (P=0.622), liver abscess (0.544), asymptomatic perihepatic fluid (0.703) or subcapsular liver hemorrhage (P=0.666) between the two groups. Due to the higher cost and adverse events of general anaesthesia, local anaesthesia may be more suitable for ablation procedures for HCC patients within the Milan criteria.

Prognostic impact of post-treatment FDG PET/CT in anal canal cancer: A prospective study

Background and purposeThe aim of our prospective study was to assess the prognostic value of 18F-FDG PET/CT performed two months post treatment for anal canal neoplasm. Population and methodsConsecutive patients with histologically proved anal cancer, with 18F-FDG PET/CT pre and two months post treatment were included. Patients were not previously treated for this neoplasm and then received radiotherapy ± chemotherapy. Clinical and pathologic data were collected and for 18F-FDG PET/CT visual and quantitative analysis (standardized uptake value, metabolic volume) were performed; response was classified according to EORTC and PERCIST criteria. The results were assessed for disease free survival and local recurrence free survival using the log-Rank test ResultsFrom December 2014 to September 2019, 94 consecutive patients were screened and 78 were included in this study. Median follow-up was 51 months. Two months post treatment, 37 patients (47.4%) had a complete radiological response according to both EORTC and PERCIST criteria, 66 patients (84.6%) had a clinical complete response. For disease free survival, the prognostic value of complete response was statistically significant (p=0.02) with 18F-FDG PET/CT and with clinical examination (p<0.001). For local recurrence free survival, the prognostic value with 18F-FDG PET/CT was lower (p=0.04) than clinical examination (p < 0.007). ConclusionWhile clinical examination remains the gold standard for post treatment evaluation in anal cancer, 18F-FDG PET/CT has a statistically significant prognostic value. These two assessments could be combined to improve early evaluation.

Risk of Local Recurrence in Men With Penile Intraepithelial Neoplasia in the Surgical Margin After Penile-sparing Surgery.

Up to 90% of men with a positive surgical margin show remaining cancer in subsequent reresections. The risk of local recurrence in men with no penile cancer but the precancerous lesion penile intraepithelial neoplasia at the surgical margin is less well studied and was the aim of this analysis. This was a retrospective analysis of men with distal penile cancer undergoing penile-sparing surgery. A competing risks survival analysis adjusted for grade, lymphovascular invasion, and stage was performed to assess local recurrence-free survival in patients with penile intraepithelial neoplasia-positive margins and completely negative surgical margins. A negative surgical margin was described in 319 men (85%), whereas penile intraepithelial neoplasia in the surgical margin was found in 59 men (15%). Local recurrence was observed in 30/319 men with a negative surgical margin compared to 11/59 men with penile intraepithelial neoplasia in the surgical margin. Adjusted for T stage and grade, patients with penile intraepithelial neoplasia at the surgical margin had a higher risk to develop a local recurrence than those with a negative surgical margin without penile intraepithelial neoplasia (HR 1.51, 95% CI 1.07-2.12, P = .019). Men with a penile intraepithelial neoplasia-positive surgical margin have an increased risk to experience local recurrence compared to men with a negative surgical margin and should undergo closer surveillance and/or adjuvant treatment.