Determining Which Patients Require Preoperative Pelvic Radiotherapy Before Curative-Intent Surgery and/or Ablation for Metastatic Rectal Cancer.

BACKGROUND: The aim of this study is to determine the optimal indications for preoperative pelvic radiotherapy (RT) in patients with metastatic rectal cancer who underwent curative-intent surgical resection and/or ablation. METHODS: Between January 2000 and October 2019, 246 patients who met our inclusion criteria were enrolled. Preoperative RT was performed in 22 patients (8.9%). Lower margin below the peritoneal reflection (p < 0.001), mesorectal fascia (MRF) invasion (p = 0.02), and lateral pelvic lymph node (LPLN) involvement (p = 0.005) were more frequent in the preoperative RT group. RESULTS: During the median follow-up period of 13.3 months (interquartile range [IQR]: 6.0-36.3 months), local recurrence (LR) was identified in 60 patients (24.4%). It was the first site of recurrence in 45 of them (18.3%). Among them, three patients were in the preoperative RT group. On multivariable analysis, lower margin below the peritoneal reflection, MRF invasion, LPLN involvement, carcinoembryonic antigen (CEA) level ≥ 10 ng/mL before treatment, and preoperative RT were significant prognostic factors for LR-free survival (LRFS). In the patient group without any risk factors, the 2-year LRFS rate was 94.9% without preoperative RT. In the patient group with one or more risk factors, the 2-year LRFS was 64.4% without and 95.2% with preoperative RT. CONCLUSION: LR developed in about 25% of patients within 2 years. Preoperative RT should be considered, especially in patients with a risk factor for LR, including lower margin below the peritoneal reflection, MRF invasion, LPLN involvement, or CEA ≥ 10 ng/mL before treatment.

Dual Oxidase 2 (DUOX2) as a Proteomic Biomarker for Predicting Treatment Response to Chemoradiation Therapy for Locally Advanced Rectal Cancer: Using High-Throughput Proteomic Analysis and Machine Learning Algorithm.

High-throughput mass-spectrometry-based quantitative proteomic analysis was performed using formalin-fixed, paraffin-embedded (FFPE) biopsy samples obtained before treatment from 13 patients with locally advanced rectal cancer (LARC), who were treated with concurrent chemoradiation therapy (CCRT) followed by surgery. Patients were divided into complete responder (CR) and non-complete responder (nCR) groups. Immunohistochemical (IHC) staining of 79 independent FFPE tissue samples was performed to validate the predictive ability of proteomic biomarker candidates. A total of 3637 proteins were identified, and the expression of 498 proteins was confirmed at significantly different levels (differentially expressed proteins-DEPs) between two groups. In Gene Ontology enrichment analyses, DEPs enriched in biological processes in the CR group included proteins linked to cytoskeletal organization, immune response processes, and vesicle-associated protein transport processes, whereas DEPs in the nCR group were associated with biosynthesis, transcription, and translation processes. Dual oxidase 2 (DUOX2) was selected as the most predictive biomarker in machine learning algorithm analysis. Further IHC validation ultimately confirmed DUOX2 as a potential biomarker for predicting the response of nCR to CCRT. In conclusion, this study suggests that the treatment response to RT may be affected by the pre-treatment tumor microenvironment. DUOX2 is a potential biomarker for the early prediction of nCR after CCRT.

Incorporating sarcopenia and inflammation with radiation therapy in patients with hepatocellular carcinoma treated with nivolumab.

BACKGROUND: We investigated the combined effects of sarcopenia and inflammation on outcomes in patients with HCC treated with nivolumab. MATERIALS AND METHODS: We reviewed 102 patients treated with nivolumab between 2017 and 2018. Sarcopenia was diagnosed when the L3 skeletal muscle indices were < 42 cm2/m2 and < 38 cm2/m2 in men and women, respectively. Baseline neutrophil-to-lymphocyte ratio (NLR) and absolute lymphocyte count were used as surrogate markers of inflammation and immune cell reservoir. High NLR (hNLR) was defined as NLR ≥ 3, and severe lymphopenia (sLP) was defined as lymphocyte < 800/µL. The overall survival (OS) and progression-free survival (PFS) were analyzed. RESULTS: With a median follow-up of 21.9 (interquartile range, 8.3-58.3) months, patients with sarcopenia showed shorter OS than those without sarcopenia (median, 2.9 vs. 7.5 months, respectively). Patients with either hNLR or sLP exhibited inferior survival than those without risk factor (median OS, 2.8 vs. 14.5 months; median PFS, 1.3 vs. 3.7 months, respectively). Among 70 patients treated with RT, benefit of RT was observed in patients with sarcopenia or those without hNLR/sLP (all p < 0.05). After multivariable analysis, RT, hNLR/sLP, albumin-bilirubin (ALBI) grade, and alpha-fetoprotein were significantly associated with OS (all p < 0.05), and hNLR/sLP was also associated with decreased PFS together with ALBI grade, alpha-fetoprotein, and RT (all p < 0.05). CONCLUSION: The current study hypothetically demonstrated that the risk group stratified by hNLR/sLP outweighs the significance of sarcopenia in predicting outcomes after nivolumab. Furthermore, patients with sarcopenia might benefit from RT, especially those without risk factors of hNLR/sLP.

Determining whether postoperative chemoradiotherapy is required in patients with pathologic T3N0 rectal cancer with negative resection margin.

PURPOSE: This study aimed to identify the risk factors for locoregional recurrence (LR) and determine possible candidates for postoperative concurrent chemoradiotherapy (CCRT) in pathologic T3N0 (pT3N0) rectal cancer patients with a negative resection margin after total mesorectal excision (TME). METHOD: Data from 365 patients who had pT3N0 rectal cancer between 2003 and 2012 in the Samsung Medical Center were reviewed. All patients underwent upfront surgery without preoperative treatment. Postoperative management involved either no adjuvant therapy (n = 122), chemotherapy alone (n = 100), or CCRT (n = 143). RESULTS: The median follow-up duration was 71 months. The 5-year overall survival, disease-free survival, and LR-free survival (LRFS) rates were 95.9%, 86.9%, and 96.3%, respectively. When comparing the three groups (surgery alone [n = 122], chemotherapy alone [n = 100], and CCRT [n = 143]), there was no significant difference in LRFS among them (94.0%, 93.4%, and 99.2%, respectively; p = 0.20). However, when patients were stratified by risk factors (distance from anal verge ≤ 5 cm and distal resection margin [DRM] ≤ 2 cm), the 5-year LRFS improved by more than 10% by adding CCRT (98.9% with CCRT vs. 87.4% without CCRT, p = 0.006) in those with more than one risk factor. Postoperative CCRT did not affect the 5-year LRFS (100% with CCRT vs. 99.0% without CCRT, p = 0.66) in patients with no risk factors. CONCLUSION: Postoperative CCRT significantly decreased LR in patients with pT3N0 rectal cancer with a negative resection margin but having a distance from the anal verge ≤ 5 cm or DRM ≤ 2 cm.

Anastomotic Leak Does Not Impact Oncologic Outcomes After Preoperative Chemoradiotherapy and Resection for Rectal Cancer.

OBJECTIVE: The aim of this study was to evaluate the relationship of anastomotic leakage, local recurrence, and overall survival in rectal cancer patients treated with preoperative chemoradiotherapy (CRT) and curative resection. BACKGROUND: Little is known about the association between anastomotic leakage and oncologic outcomes after preoperative CRT. METHODS: A total of 698 consecutive primary rectal cancer patients after preoperative CRT between April 19, 2000, and December 27, 2013, were retrospectively reviewed. Forty-seven patients who had anastomotic leakage were compared with 651 patients who had no anastomotic leakage. RESULTS: Of 698 patients, 47 (6.7%) patients had anastomotic leakage. Among these 47 patients, 39 (83.0%) had grade C leak that required urgent operation, while 8 (17.0%) had grade B leak that was managed expectantly or by percutaneous drainage. The median follow-up period was 47.6 months (range, 27.1 to 68.9 months). One hundred twenty (17.2%) recurrences were identified among all patients. The median overall disease-free survival was 43 months (range, 22.4 to 66.7 months). Five-year disease-free survival did not differ significantly between the 2 groups (80.5% vs 80.4%, P = 0.839). Five-year local recurrence-free survival did not differ significantly either between the 2 groups (93.7% vs 94.9%, P = 0.653). Five-year overall survival rates of patients with or without leakage were 90.9% and 86.3%, respectively (P = 0.242). Five-year cancer-specific survival rates of patients with or without leakage were 92.2% and 86.3%, respectively (P = 0.248). CONCLUSION: After preoperative CRT, an anastomotic leak is not associated with a significant increase in local recurrence or long-term survival in rectal cancer.

Indistinguishable T2/T3-N0 rectal cancer on rectal magnetic resonance imaging: comparison of surgery-first and neoadjuvant chemoradiation therapy-first strategies.

PURPOSE: We compared the treatment outcome between surgery-first and neoadjuvant chemoradiation therapy (nCRT)-first strategies in patients with indistinguishable T2/T3-N0 rectal cancer on rectal magnetic resonance imaging (MRI). METHODS: Our institutional review board approved this retrospective study, and informed consent was waived. Among 1910 patients who underwent rectal MRI between 2008 and 2012, 79 patients (mean age, 59.4 years, 49 men and 30 women) who had indistinguishable T2/T3-N0 rectal cancer on rectal MRI were included. Local recurrence-free survival (LRFS), recurrence-free survival (RFS), overall survival (OS), and disease-specific survival (DSS) were compared between the two groups. Treatment-related complications were evaluated. RESULTS: Among 79 patients, 51 were treated by surgery first and 28 were treated by nCRT first. In comparison of survival of the surgery- and nCRT-first groups at 5 years, the LRFS rate was 95.6 and 96.3%, RFS rate was 91.0 and 92.4%, OS rate was 93.7 and 92.6%, and DSS rate was 98.0 and 92.6%, respectively. LRFS, RFS, OS, and DSS showed no significant difference between the two groups (p = 0.862, 0.677, 0.953, and 0.479). The complication rate was not significantly different between the groups (20.0% for surgery-first group vs. 10.7% for nCRT-first group, p = 0.357). CONCLUSION: Treatment outcomes were not significantly different between surgery-first and nCRT-first strategies for indistinguishable T2/T3-N0 rectal cancer on rectal MRI.

Radiotherapeutic strategies for hepatocellular carcinoma with portal vein tumour thrombosis in a hepatitis B endemic area.

BACKGROUND & AIMS: This nationwide, multicenter study investigated treatment outcomes as well as the optimal radiotherapeutic strategy in patients with hepatocellular carcinoma (HCC) and portal vein tumour thrombosis (PVTT). METHODS: We retrospectively reviewed the records of 985 patients who received radiotherapy (RT) for PVTT. The median equivalent RT dose was 48.75 Gy. Combined treatment, defined as liver-directed treatments performed within a month of RT, was administered to 657 patients (66.7%). The PVTT and primary tumour were irradiated in 413 patients (41.9%), and PVTT only was targeted in 572 patients (58.1%). RESULTS: The response rate of the PVTT was 51.8%, and RT responders had a significantly longer survival than non-responders (15.2 vs. 6.9 months). Equivalent RT dose and combined treatment predicted response of PVTT. The median overall survival (OS) was 10.2 months. Multivariate analysis revealed the equivalent RT dose ˃45 Gy and combined treatment as significant positive factors for OS. In the propensity score matching analysis, the combined treatment group had better OS than the no combined treatment group, whereas the OS of the PVTT + primary tumour group did not differ significantly from that of the PVTT only group. CONCLUSION: The equivalent RT dose ˃45 Gy, given in combination with other treatments, provided better PVTT control and OS. The optimal RT volume is suggested for either PVTT + primary or PVTT only. Taken together, multimodal treatment with equivalent RT dose higher than 45 Gy is recommended for patients with HCC and PVTT.

Predictive factors of gastroduodenal bleeding after postoperative radiotherapy in biliary tract cancer.

OBJECTIVE: To identify predictive factors for gastroduodenal bleeding after postoperative radiation therapy in patients with biliary tract cancer. METHODS: We identified 186 patients with biliary tract cancer who completed scheduled postoperative radiation therapy from March 2000 to August 2013. To isolate the effects of radiation on gastroduodenal bleeding, patients with pylorus-preserving pancreaticoduodenectomy, pylorus-resecting pancreaticoduodenectomy or Whipple surgery (n = 67) were excluded from this analysis. Postoperative radiation therapy was started at a median 5 weeks (range: 4-12 weeks) after surgery with a median dose of 44 Gy (range: 44-54), and chemotherapy was also concurrently administered to 102 patients. RESULTS: The median age of the patients was 59 years (range: 36-76 years). Of the 119 patients, 26 had intrahepatic cholangiocarcinoma, 29 had hilar cholangiocarcinoma, while 64 had extrahepatic tumors (gallbladder cancer, n = 53; proximal bile duct cancer, n = 10; choledochal cyst cancer, n = 1). Of all, 11 patients (9%) developed gastroduodenal bleeding. In univariate analyses, hepatic artery resection and gastroduodenal wall thickening on postoperative radiation therapy simulation computed tomography were statistically significant factors for gastroduodenal bleeding. Multivariate analysis by a logistic regression model using those two variables revealed that both parameters were independent predictors for gastroduodenal bleeding. CONCLUSIONS: Concomitant hepatic artery resection and presence of gastroduodenal wall thickening on postoperative radiation therapy simulation computed tomography were predictive factors for gastroduodenal bleeding after postoperative radiation therapy in biliary tract cancer. In such cases, patients should be informed of the high risk of gastroduodenal bleeding, and should be closely observed during and after postoperative radiation therapy.

Combination treatment of trans-arterial chemo-embolisation, radiotherapy and hyperthermia (CERT) for hepatocellular carcinoma with portal vein tumour thrombosis: Interim analysis of prospective phase II trial.

Objectives This study evaluated the objective response to and toxicity of trans-arterial chemo-embolisation (TACE) followed by radiotherapy and hyperthermia (CERT) in hepatocellular carcinoma patients with portal vein tumour thrombosis. Methods The study design was a single-centre prospective phase II trial. Patients were first treated with TACE, with the first hyperthermia session 1 week later. Respiration-gated radiotherapy (RT) was delivered in 10 fractions of 3-5 Gy after another week. Six sessions of hyperthermia were delivered twice a week according to an energy escalation protocol. Response evaluation was planned at 1 month after RT completion using the modified Response Evaluation Criteria in Solid Tumors (RECIST). Toxicity was determined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Results Interim analysis was conducted on patients enrolled from October 2013 to November 2014. During this period, 46 patients (90.2%) who received at least one hyperthermia session were eligible and enrolled. Median follow-up was 6.7 months (range 2.0-15.0 months). Complete response was observed in 10 (21.7%) patients and partial response in 27 (47.8%). Most toxicities were grade I or II. One death was related to severe pneumonia of unknown cause in the left lung and one patient could not complete planned treatment because of continuous elevation of bilirubin after TACE. Late, asymptomatic gastroduodenal toxicities were noticed in 13 (28.3%) patients. Conclusion Preliminary evaluation of CERT showed a promising response rate with acceptable toxicities.

Predictors and patterns of recurrence after curative liver resection in intrahepatic cholangiocarcinoma, for application of postoperative radiotherapy: a retrospective study.

BACKGROUND: The majority of patients with intrahepatic cholangiocarcinoma (IHCC) who undergo complete tumor resection subsequently develop tumor recurrence. The objectives of this study were to determine the risk factors for IHCC recurrence after curative (R0) liver resection and to identify the feasibility about postoperative adjuvant radiation therapy (RT). METHODS: We retrospectively reviewed patients who underwent liver resection for IHCC between April 1995 and December 2012 at Samsung Medical Center. Cox regression analysis was performed to determine risk factors of recurrence. Patients with a recurrence in remnant liver within 2 cm from the resection margin, with or without locoregional lymph node (LN) metastases, were considered as potential RT candidates. Center-of-mass (COM) distances between the recurrent cancers and the cut surface were measured with MATLAB. RESULTS: We included 153 out of 198 patients who underwent partial liver resection for IHCC. About two thirds (n=93, 60.8%) of patients developed recurrent disease. The median recurrence-free survival (RFS) was 14 months (range, 0-204). Tumor size≥4.0 cm, LN metastasis and multiple tumors were significant predictors of IHCC recurrence on multivariate analysis. Tumor size≥5.0 cm was the only factor associated with recurrence beyond the RT field in patients with recurrence. Among 93 patients with recurrence, 16 (17.2%) patients were recurred in the RT field. CONCLUSION: After curative resection in IHCC, more than 60% of patients recurred, and among recurred patients, 17.2% were recurred within the RT field. Consequently, for control of locoregional recurrence, adjuvant RT could be carefully considered in patients with recurrence factors. Especially, patients with a tumor size larger than 5 cm should be judiciously selected for adjuvant RT.

The feasibility of combined transcatheter arterial chemoembolization and radiotherapy for advanced hepatocellular carcinoma.

BACKGROUND & AIMS: Sorafenib is regarded as the standard treatment of care in Barcelona Clinic Liver Cancer (BCLC) stage C patients. However, the modest overall survival (OS) and disease control rate warrants for a better treatment modality. This study aimed to investigate the feasibility of combined transarterial chemoembolization and radiotherapy (TACE+RT) in comparison with sorafenib for advanced hepatocellular carcinoma (HCC). METHODS AND MATERIALS: From 2007 to 2011, a total of 116 patients with locally advanced HCC were retrospectively enrolled. Sixty-seven patients treated with TACE+RT were compared with 49 patients treated with sorafenib. Propensity score matching generated a matched cohort composed of 27 patients from each group. OS was the primary endpoint for the analysis. RESULTS: At baseline, the sorafenib group had a tendency for a tumour size ≥10 cm, presence of lymph node metastasis and main portal vein tumour thrombosis compared to the TACE+RT group. The OS in the TACE+RT group was significantly longer compared to the sorafenib group (14.1 months vs. 3.3 months, P < 0.001). In the propensity score-matched cohort, baseline characteristics did not differ between the two groups. The TACE+RT group showed prolonged OS compared to the sorafenib group (6.7 months vs. 3.1 months, P < 0.001). Multivariate analysis revealed that TACE+RT was the only independent prognostic factor associated with survival in the propensity score-matched cohort (HR = 0.172, P < 0.001). CONCLUSIONS: The OS of TACE+RT was longer compared to sorafenib treatment in locally advanced HCC patients without distant metastasis. Further prospective studies are warranted to confirm these findings.

Considerations for radiation therapy in hepatocellular carcinoma: the radiation oncologists' perspective.

Although the Barcelona Clinic Liver Cancer staging system does not recommend radiation therapy (RT) as a locoregional modality in hepatocellular carcinoma (HCC), many prospective and retrospective studies have reported excellent local control with favorable survival rates after RT using modern techniques. Additionally, there have been several comparative or meta-analysis results reporting the superiority of RT in unresectable HCC. Therefore, it might be more reasonable to apply RT in unresectable HCC as an alternative locoregional modality to improve local control in HCC. However, several considerations for the application of RT in HCC exist. The considerations for RT in HCC are purpose, combination treatment and technique. The purpose of RT should be based on baseline liver status as well as tumor extent and location. There are several reasonable advantages in local, intrahepatic and extrahepatic control when combined with other modalities, but it could lead to overtreatment in some cases. The technical considerations according to the purpose and combination modality are the final step. For the application of RT in HCC, the purpose of RT, combination strategy and technical considerations should be taken into account.

Combined High-Dose Radiotherapy with Sequential Gemcitabine-Cisplatin Based Chemotherapy Increase the Resectability and Survival in Locally Advanced Unresectable Intrahepatic Cholangiocarcinoma: A Multi-institutional Cohort Study.

PURPOSE: The locally advanced unresectable intrahepatic cholangiocarcinoma (ICC) has detrimental oncological outcomes. In this study, we aimed to investigate the efficacy of radiotherapy in patients with locally advanced unresectable ICC. MATERIALS AND METHODS: Between 2001 and 2021, 116 patients were identified through medical record who underwent radiotherapy for locally advanced unresectable ICC. The resectability of ICC is determined by the multidisciplinary team at each institution. Overall survival (OS) were analyzed using the Kaplan-Meier method, and prognostic factors were analyzed using the Cox proportional hazards model. RESULTS: The median equivalent radiotherapy dose in 2 Gy fractions (EQD2) was 52 Gy (range, 30 to 110 Gy). Forty-seven patients (40.5%) received sequential gemcitabine-cisplatin based chemotherapy (GEM-CIS CTx). Multivariate analysis identified two risk factors, EQD2 of ≥ 60 Gy and application of sequential GEM-CIS CTx for OS. Patients were grouped by these two risk factors: group 1, EQD2 ≥ 60 Gy with sequential GEM-CIS CTx (n=25); group 2, EQD2 < 60 Gy with sequential GEM-CIS CTx or fluoropyrimidine-based concurrent chemoradiotherapy (n=70); and group 3, radiotherapy alone (n=21). Curative resection was more frequently undergone in group 1 than in groups 2 or 3 (28% vs. 8.6% vs. 0%, respectively). Consequently, OS was significantly better in group 1 than in groups 2 and 3 (p < 0.05). CONCLUSION: Combined high-dose radiotherapy with sequential GEM-CIS CTx improved oncologic outcomes in patients with locally advanced unresectable ICC. Further prospective studies are required to validate these findings.

Proton Beam Radiotherapy as a Curative Alternative to Radiofrequency Ablation for Newly Diagnosed Hepatocellular Carcinoma.

BACKGROUND/AIM: This study aimed to compare the oncological outcomes of proton beam radiotherapy (PBT) with those of radiofrequency ablation (RFA) for newly diagnosed hepatocellular carcinoma (HCC). PATIENTS AND METHODS: This study included 323 patients who underwent PBT (n=40) or RFA (n=283) as a curative treatment for previously untreated HCC between October 2016 and June 2021. The primary endpoints were local progression and toxicity. RESULTS: The median follow-up was 3.4 years (range=1.1-5.7 years). In terms of portal vein tumor thrombosis, tumor size, alpha-fetoprotein, and prothrombin-induced by vitamin K absence-II, the PBT group had significantly more severe tumor burdens than those of the RFA group (p<0.0001, p<0.0001, p=0.0004, and p<0.0001, respectively). No significant difference was observed in cumulative local progression rate (10.4% in PBT vs. 7.8% in RFA at 3-years, p=0.895). Grade 3 or higher toxicity was reported in only one patient (0.4%) after RFA. Multivariable analysis demonstrated that treatment modality was not a significant prognostic factor for local progression (hazard ratio=1.05; 95% confidence interval=0.32-3.48; p=0.934). CONCLUSION: PBT demonstrated comparable local control with acceptable toxicity to RFA in newly diagnosed HCC. Therefore, PBT may be a valid alternative.

Risk Factors for Distant Metastasis in Extrahepatic Bile Duct Cancer after Curative Resection (KROG 1814).

PURPOSE: Risk factors predicting distant metastasis (DM) in extrahepatic bile duct cancer (EHBDC) patients treated with curative resection were investigated. MATERIALS AND METHODS: Medical records of 1,418 EHBDC patients undergoing curative resection between Jan 2000 and Dec 2015 from 14 institutions were reviewed. After resection, 924 patients (67.6%) were surveilled without adjuvant therapy, 297 (21.7%) were treated with concurrent chemoradiotherapy (CCRT) and 148 (10.8%) with CCRT followed by chemotherapy. To exclude the treatment effect from innate confounders, patients not treated with adjuvant therapy were evaluated. RESULTS: After a median follow-up of 36.7 months (range, 2.7 to 213.2 months), the 5-year distant metastasis-free survival (DMFS) rate was 57.7%. On multivariate analysis, perihilar or diffuse tumor (hazard ratio [HR], 1.391; p=0.004), poorly differentiated histology (HR, 2.014; p < 0.001), presence of perineural invasion (HR, 1.768; p < 0.001), positive nodal metastasis (HR, 2.670; p < 0.001) and preoperative carbohydrate antigen (CA) 19-9 ≥ 37 U/mL (HR, 1.353; p < 0.001) were significantly associated with inferior DMFS. The DMFS rates significantly differed according to the number of these risk factors. For validation, patients who underwent adjuvant therapy were evaluated. In patients with ≥ 3 factors, additional chemotherapy after CCRT resulted in a superior DMFS compared with CCRT alone (5-year rate, 47.6% vs. 27.7%; p=0.001), but the benefit of additional chemotherapy was not observed in patients with 0-2 risk factors. CONCLUSION: Tumor location, histologic differentiation, perineural invasion, lymph node metastasis, and preoperative CA 19-9 level predicted DM risk in resected EHBDC. These risk factors might help identifying a subset of patients who could benefit from additional chemotherapy after resection.

Impact and optimal timing of local therapy addition in borderline resectable or locally advanced pancreatic cancer after FOLFIRINOX chemotherapy.

Background: To evaluate the efficacy and optimal timing of local treatment in patients with borderline resectable (BR) or locally advanced pancreatic cancer (LAPC) treated with upfront FOLFIRINOX. Method: Between 2015 and 2020, 258 patients with pancreatic ductal adenocarcinoma (PDAC) were analysed. Treatment outcomes were compared between systemic treatment group (ST) and multimodality treatment groups (MT) using Kaplan-Meier curves and log-rank test. The MT were stratified as follows: FOLFIRINOX + radiation therapy (RT) (MT1), FOLFIRINOX + surgical resection (MT2), and FOLFIRINOX + RT + surgical resection (MT3). Results: With median follow-up period of 18 months, the 2-year overall survival (OS) for the ST was 22.0%, and it was significantly worse than MT (MT1, 46.3%; MT2, 65.7% and MT3; 90.2%; P < .001). The 2-year locoregional progression free survival (LRPFS) and overall PFS in ST were 10.7% and 7.0%, which were also significantly lower than those of MT (2-year LRPFS: MT1, 31.8%; MT2, 45.3%; MT3, 81.0%; 2-year overall PFS: MT1, 23.3%; MT2, 35.0%; MT3, 66.3%; P < .001). In time-varying multivariate Cox proportional hazard model, local treatment contributed to better treatment outcomes, with adjusted hazard ratios of 0.568 (95% confidence interval [CI], 0.398-0.811), 0.490 (95% CI, 0.331-0.726), and 0.656 (95% CI, 0.458-0.940) for OS, LRPFS, and overall PFS, respectively. The time window of 11-17 months after FOLFIRINOX appeared to demonstrate the maximal efficacy of local treatments in OS. Conclusions: Adding local treatment in BR/LAPC patients treated with upfront FOLFIRINOX seemed to contribute in improved treatment outcomes, and it showed maximal efficacy in OS when applied 11-17 months after the initiation of FOLFIRINOX. We suggest that administration of sufficient period of upfront FOLFIRINOX may intensify the efficacy of local treatments, and well controlled prospective trials are expected.

Clinical outcomes of neoadjuvant chemoradiotherapy followed by total mesorectal excision in locally advanced rectal cancer with mesorectal fascia involvement.

PURPOSE: For the treatment of locally advanced rectal cancer (LARC), research on primary lesions with mesorectal fascia (MRF) involvement is lacking. This study analyzed the clinical outcomes and efficacy of dose-escalated neoadjuvant concurrent chemoradiotherapy (NCRT) to patients with LARC involving MRF. MATERIALS AND METHODS: We retrospectively reviewed 301 patients who were diagnosed with LARC involving MRF and underwent NCRT followed by total mesorectal excision (TME). Patients who received radiotherapy (RT) doses of ≤50.4 Gy were defined as the non-boost group, while ≥54.0 Gy as the boost group. Pathological tumor response and survival outcomes, including intrapelvic recurrence-free survival (IPRFS), distant metastases-free survival (DMFS) and overall survival (OS), were analyzed. RESULTS: A total of 269 patients (89.4%) achieved a negative pathological circumferential resection margin and 104 (34.6%) had good pathological tumor regression grades. With a median follow-up of 32.4 months, IPRFS, DMFS, and OS rates at 5-years were 88.6%, 78.0%, and 91.2%, respectively. In the subgroup analysis by RT dose, the boost group included more advanced clinical stages of patients. For the non-boost group and boost group, 5-year IPRFS rates were 90.3% and 87.0% (p = 0.242), 5-year DMFS rates were 82.0% and 71.3% (p = 0.105), and 5-year OS rates were 93.0% and 80.6% (p = 0.439), respectively. Treatment related toxicity was comparable between the two groups (p = 0.211). CONCLUSION: Although this retrospective study failed to confirm the efficacy of dose-escalated NCRT, favorable IPRFS and pathological complete response was achieved with NCRT followed by TME. Further studies combining patient customized RT dose with systemic therapies are needed.

Practice guidelines for managing extrahepatic biliary tract cancers.

Backgrounds/Aims: Reported incidence of extrahepatic bile duct cancer is higher in Asians than in Western populations. Korea, in particular, is one of the countries with the highest incidence rates of extrahepatic bile duct cancer in the world. Although research and innovative therapeutic modalities for extrahepatic bile duct cancer are emerging, clinical guidelines are currently unavailable in Korea. The Korean Society of Hepato-Biliary-Pancreatic Surgery in collaboration with related societies (Korean Pancreatic and Biliary Surgery Society, Korean Society of Abdominal Radiology, Korean Society of Medical Oncology, Korean Society of Radiation Oncology, Korean Society of Pathologists, and Korean Society of Nuclear Medicine) decided to establish clinical guideline for extrahepatic bile duct cancer in June 2021. Methods: Contents of the guidelines were developed through subgroup meetings for each key question and a preliminary draft was finalized through a Clinical Guidelines Committee workshop. Results: In November 2021, the finalized draft was presented for public scrutiny during a formal hearing. Conclusions: The extrahepatic guideline committee believed that this guideline could be helpful in the treatment of patients.

Prophylactic supraclavicular radiotherapy after surgery in high-risk n1 breast cancer.

OBJECTIVES: To evaluate the role of prophylactic supraclavicular radiotherapy (RT) by comparing the clinical outcomes of locoregional recurrence (LRR) in high-risk N1 breast cancer. METHODS: We performed a retrospective comparison study of 250 high-risk N1 breast cancer patients treated at two institutions. Patients were considered to be high-risk when they had more than two of the following risk factors: lymphovascular invasion, extracapsular extension, metastasis to more than two axillary lymph nodes (ALNs), or level II or higher ALN metastasis. We compared two groups treated with different adjuvant RT fields for the purpose of prophylactic supraclavicular RT (SCRT). RESULTS: Among the 250 patients, 97 patients received SCRT while 153 did not. During follow-up, 32 patients (7 in the SCRT and 25 in the no-SCRT group) had recurrence, and LRR developed in 19 patients, 18 of whom had not received SCRT. In multivariate analysis, SCRT [hazard ratio (HR) 0.072; p = 0.011] and chemotherapy regimen (cyclophosphamide, Adriamycin, and taxane; TAC) were the significant prognostic factors in LRR-free survival (HR 0.385; p = 0.046), and chemotherapy regimen also showed significance for distant metastasis-free survival (HR 0.399; p = 0.037). CONCLUSIONS: Use of prophylactic SCRT may reduce the risk of LRR in patients with high-risk N1 breast cancer.