Prognostic impact of neutrophilia and lymphopenia on survival in anal cancer treated with definitive concurrent chemoradiotherapy: a retrospective multicenter study.

PURPOSE: This study evaluated the prognostic value of leukocyte, lymphocyte, and neutrophil counts in anal cancer patients undergoing concurrent chemoradiotherapy (CCRT). METHODS: Multi-institutional retrospective data review included 148 non-metastatic anal cancer patients treated with definitive CCRT with 5-fluorouracil plus mitomycin C between the year 2001 and 2019. The median radiation dose to the primary tumor was 54 Gy with a median pelvic dose of 45 Gy. Median follow-up duration was 56 months, and complete blood cell counts were analyzed from baseline to 1 year after the completion of radiotherapy. RESULTS: Although most patients showed a normal number of blood cells before treatment, 6.1% and 4.1% of patients showed leukocytosis (> 10,000/µl) and neutrophilia (> 7500/µl), respectively. After the initiation of treatment, seven patients (4.7%) displayed grade 4 lymphopenia (< 200/µl) at 1 month. Patients with initial leukocytosis showed inferior progression- and locoregional progression-free survival, and neutrophilia was a prognostic factor in all survival outcomes. Grade 4 lymphopenia at 1 month was also significantly associated with overall, progression-, and distant metastasis-free survival. On multivariate analyses, baseline neutrophilia was associated with 56.8-, 22.6-, 10.7-, and 23.0-fold increased risks of death, disease relapse, locoregional progression, and distant metastasis, respectively. Furthermore, lymphocytes < 200/µl at 1 month was linked to 6.8-, 5.4-, and 6.3-fold increased risks for death, disease relapse, and distant metastasis, respectively. CONCLUSION: The number of leukocytes, lymphocytes, and neutrophils readily acquired from routine blood tests before and during treatment could be an independent prognostic factor of survival in patients with anal cancer.

Nomogram prediction of survival in patients with brain metastases from hepatocellular carcinoma treated with whole-brain radiotherapy: a multicenter retrospective study.

The incidence of brain metastasis from hepatocellular carcinoma (HCC) is increasing because of the improved survival outcome of HCC patients, but the prognosis of these patients is extremely poor. HCC patients with brain metastasis were investigated to identify their prognostic factors for overall survival. Patients with brain metastasis from HCC who had been treated with whole-brain radiotherapy (WBRT) in five hospitals were enrolled in the study. The medical records of the patients were reviewed, and the clinical factors were analyzed to identify the prognostic factors for overall survival. Of the total of 97 patients who were enrolled in the study, 83 were male and the median age at the brain metastases was 56.6 years. Motor weakness (43.3 %) and headache (41.2 %) were common presenting symptoms. The median AFP level was 4180 ng/ml, and 81 patients were assessed as belonging to Child-Pugh classification A upon the diagnosis of brain metastasis. WBRT alone in 71 patients, surgery or radiosurgery combined with WBRT as the adjuvant setting in 18 patients, and WBRT as salvage treatment in 8 patients were performed. The median overall survival of the patients was 3.5 months. In the multivariate analysis, the ECOG performance status (PS), Child-Pugh classification, AFP, and treatment aim showed significant association with the overall survival of the patients. Based on these factors, a nomogram predicting the prognosis was developed. The concordance index of the nomogram was 0.74, and the prediction was well calibrated. In conclusion, the survival outcome of patients with brain metastasis from HCC can be predicted with the nomogram constructed from the ECOG PS, Child-Pugh classification, AFP, and treatment aim.

Radiation Oncologists' Perspectives on Oligometastatic Prostate Cancer: A Survey from Korean Oligometastasis Working Group.

BACKGROUND: Interest in the oligometastatic prostate cancer (OMPC) is increasing, and various clinical studies have reported the benefits of metastasis-directed radiation therapy (MDRT) in OMPC. However, the recognition regarding the adopted definitions, methodologies of assessment, and therapeutic approaches is diverse among radiation oncologists. This study aims to evaluate the level of agreement for issues in OMPC among radiation oncologists. METHODS: We generated 15 key questions (KQs) for OMPC relevant to definition, diagnosis, local therapies, and endpoints. Additionally, three clinical scenarios representing synchronous metastatic prostate cancer (mPC) (case 1), metachronous mPC with visceral metastasis (case 2), and metachronous mPC with castration-resistance and history of polymetastasis (case 3) were developed. The 15 KQs were adapted according to each scenario and transformed into 23 questions with 6-9 per scenario. The survey was distributed to 80 radiation oncologists throughout the Republic of Korea. Answer options with 0.0-29.9%, 30-49.9%, 50-69.9%, 70-79.9%, 80-89.9%, and 90-100% agreements were considered as no, minimal, weak, moderate, strong, and near perfect agreement, respectively. RESULTS: Forty-five candidates voluntarily participated in this study. Among 23 questions, near perfect (n = 4), strong (n = 3), or moderate (n = 2) agreements were shown in nine. For the case recognized as OMPC with agreements of 93% (case 1), near perfect agreements on the application of definitive radiation therapy (RT) for whole metastatic lesions were achieved. While ≥70% agreements regarding optimal dose-fractionation for metastasis-directed RT (MDRT) has not been achieved, stereotactic body RT (SBRT) is favored by clinicians with higher clinical volume. CONCLUSION: For the case recognized as OMPC, near perfect agreement for the application of definitive RT for whole metastatic lesions was reached. SBRT was more favored as a MDRT by clinicians with a higher clinical volume.

Radiation Oncologists' Perspectives on Oligometastatic Disease: A Korean Survey Study.

PURPOSE: Perspectives of radiation oncologists on oligometastatic disease was investigated using multi-layered survey. MATERIALS AND METHODS: Online survey on the oligometastatic disease was distributed to the board-certified regular members of the Korean Society for Radiation Oncology. The questionnaire consisted of four domains: five questions on demographics; five on the definition of oligometastatic disease; four on the role of local therapy; and three on the oligometastatic disease classification, respectively. RESULTS: A total of 135 radiation oncologists participated in the survey. The median length of practice after board certification was 22.5 years (range, 1 to 44 years), and the vast majority (94.1%) answered affirmatively to the clinical experience in oligometastatic disease management. Nearly two-thirds of the respondents considered the number of involved organs as an independent factor in defining oligometastasis. Most frequently perceived upper limit on the numerical definition of oligometastasis was 5 (64.2%), followed by 3 (26.0%), respectively. Peritoneal and brain metastasis were nominated as the sites to be excluded from oligometastastic disease by 56.3% and 12.6% of the participants, respectively. Vast majority (82.1%) agreed on the role of local treatment in the management of oligometastatic disease. Majority (72%) of the participants acknowledged the European Society for Radiotherapy and Oncology (ESTRO)-European Organisation for Research and Treatment of Cancer (EORTC) classification of oligometastatic disease, however, only 43.3% answered that they applied this classification in their clinical practice. Underlying reasons against the clinical use were 'too complicated' (66.0%), followed by 'insufficient supporting evidence' (30.0%), respectively. CONCLUSION: While most radiation oncologists supported the role of local therapy in oligometastatic disease, there were several inconsistencies in defining and categorizing oligometastatic disease. Continued education and training on oligometastatic disease would be also required to build consensus among participating caregivers.

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.

Locoregional Recurrence in Adenoid Cystic Carcinoma of the Breast: A Retrospective, Multicenter Study (KROG 22-14).

Purpose: This study aims to evaluate the treatment approaches and locoregional patterns for Adenoid cystic carcinoma (ACC) in the breast, which is an uncommon malignant tumor with limited clinical data. Materials and Methods: A total of 93 patients diagnosed with primary ACC in the breast between 1992 and 2022 were collected from multi-institutions. All patients underwent surgical resection, including breast-conserving surgery (BCS) or total mastectomy (TM). The recurrence patterns and locoregional recurrence-free survival (LRFS) were assessed. Results: Seventy-five patients (80.7%) underwent BCS, and 71 of them (94.7%) received post-operative radiation therapy (PORT). Eighteen patients (19.3%) underwent TM, with 5 of them (27.8%) also receiving PORT. With a median follow-up of 50 months, the LRFS rate was 84.2% at 5 years. Local recurrence (LR) was observed in 5 patients (5.4%) and 4 cases (80%) of the LR occurred in the tumor bed. Three of LR (3/75, 4.0%) had a history of BCS and PORT, meanwhile, two of LR (2/18, 11.1%) had a history of mastectomy. Regional recurrence occurred in 2 patients (2.2%), and both cases had a history of PORT with (n=1) and without (n=1) irradiation of the regional lymph nodes. Partial breast irradiation (p=0.35), BCS (p=0.96) and PORT in BCS group (p=0.33) had no significant association with LRFS. Conclusion: BCS followed by PORT was the predominant treatment approach for ACC of the breast and local recurrence mostly occurred in the tumor bed. The findings of this study suggest that partial breast irradiation might be considered for PORT in primary breast ACC.

Assessment of deep learning-based auto-contouring on interobserver consistency in target volume and organs-at-risk delineation for breast cancer: Implications for RTQA program in a multi-institutional study.

PURPOSE: To quantify interobserver variation (IOV) in target volume and organs-at-risk (OAR) contouring across 31 institutions in breast cancer cases and to explore the clinical utility of deep learning (DL)-based auto-contouring in reducing potential IOV. METHODS AND MATERIALS: In phase 1, two breast cancer cases were randomly selected and distributed to multiple institutions for contouring six clinical target volumes (CTVs) and eight OAR. In Phase 2, auto-contour sets were generated using a previously published DL Breast segmentation model and were made available for all participants. The difference in IOV of submitted contours in phases 1 and 2 was investigated quantitatively using the Dice similarity coefficient (DSC) and Hausdorff distance (HD). The qualitative analysis involved using contour heat maps to visualize the extent and location of these variations and the required modification. RESULTS: Over 800 pairwise comparisons were analysed for each structure in each case. Quantitative phase 2 metrics showed significant improvement in the mean DSC (from 0.69 to 0.77) and HD (from 34.9 to 17.9 mm). Quantitative analysis showed increased interobserver agreement in phase 2, specifically for CTV structures (5-19 %), leading to fewer manual adjustments. Underlying IOV differences causes were reported using a questionnaire and hierarchical clustering analysis based on the volume of CTVs. CONCLUSION: DL-based auto-contours improved the contour agreement for OARs and CTVs significantly, both qualitatively and quantitatively, suggesting its potential role in minimizing radiation therapy protocol deviation.

Abscopal effect in metastatic breast cancer treated with stereotactic body radiotherapy in the absence of immunotherapy.

Purpose: In this study, we aimed to assess the abscopal effect (AE) after CyberKnife stereotactic body radiotherapy (SBRT) in metastatic breast cancer patients without immunotherapy. Methods: We reviewed breast cancer patients who received SBRT with a fraction size of ≥ 6 Gy for metastatic lesions between July 2008 and December 2021. We selected patients who had at least one measurable extracranial lesion in addition to SBRT target lesions and were not treated with immunotherapy. A total of 40 SBRT cases from 34 patients were included in the analysis. The AE was defined as occurring before the overall progression of the disease, regardless of the use of systemic treatment. Results: The median follow-up duration was 16.4 months. Among 40 SBRT cases, the AE was observed in 10 (25.0%) with a median interval of 2.1 months. Of these lesions, 70.0% did not progress for one year. In multivariate logistic regression analysis, no change in systemic treatment after SBRT was significantly associated with an increase in the AE (odds ratio [OR] = 1.428, 95% confidence interval [CI] = 1.108 - 1.841, p = 0.009). A post-SBRT neutrophil-to-lymphocyte ratio (NLR) of < 2 marginally increased the AE (OR = 1.275, 95% CI = 0.998 - 1.629, p = 0.060). However, a high SBRT dose and large planning target volume did not (p = 0.858 and 0.152, respectively) in univariate analysis. Conclusions: One out of four patients experienced the AE after SBRT in the absence of immunotherapy. The AE could occur more frequently when systemic treatment remains unchanged, and patients have a low NLR after SBRT.

Patterns of locoregional recurrences and suggestion of the clinical target volume in resected perihilar extrahepatic cholangiocarcinoma.

Purpose: To evaluate the patterns of locoregional recurrence (LRR) in patients with perihilar extrahepatic cholangiocarcinoma (PEHC) treated with radical resection and to suggest the optimal target volume for elective nodal irradiation. Methods: Medical records of PEHC patients who underwent radical resection between January 2000 and September 2021 at five institutions were reviewed. Patients who were confirmed with LRR in the follow-up imaging study were included. The LRR sites were mapped onto the corresponding sites in template computed tomography images. The margin around the vascular structure was investigated to generate the clinical target volume (CTV) covering the common sites of regional recurrences. Results: A total of 87 LRRs in 46 patients were identified, 29 (33.3%) of which were local recurrences and 58 (66.7%) were regional recurrences. The most common site of local recurrence was the liver resection margin (n = 16), followed by the anastomosis site (n = 8). Regional recurrences were observed most commonly in the para-aortic area (n = 13), followed by in the aortocaval space (n = 11), portal vein area (n = 11), and portocaval area (n = 9). Nodal CTV was generated by adding an individualized margin around the portal vein, aorta, common hepatic artery, celiac artery, and left gastric artery. Conclusions: The LRR patterns in the resected PEHC were evaluated and specific guidelines for nodal CTV delineation were provided, which may help physicians delineating the target volume in postoperative radiotherapy for PEHC. These findings need further validation in a lager cohort.

Differential Perspectives by Specialty on Oligometastatic Colorectal Cancer: A Korean Oligometastasis Working Group's Comparative Survey Study.

PURPOSE: Despite numerous studies on the optimal treatments for oligometastatic disease (OMD), there is no established interdisciplinary consensus on its diagnosis or classification. This survey-based study aimed to analyze the differential opinions of colorectal surgeons and radiation oncologists regarding the definition and treatment of OMD from the colorectal primary. MATERIALS AND METHODS: A total of 141 participants were included in this study, consisting of 63 radiation oncologists (44.7%) and 78 colorectal surgeons (55.3%). The survey consisted of 19 questions related to OMD, and the responses were analyzed using the chi-square test to determine statistical differences between the specialties. RESULTS: The radiation oncologists chose "bone" more frequently compared to the colorectal surgeons (19.2% vs. 36.5%, p=0.022), while colorectal surgeons favored "peritoneal seeding" (26.9% vs. 9.5%, p=0.009). Regarding the number of metastatic tumors, 48.3% of colorectal surgeons responded that "irrelevant, if all metastatic lesions are amendable to local therapy", while only 21.8% of radiation oncologist chose same answer. When asked about molecular diagnosis, most surgeons (74.8%) said it was important, but only 35.8% of radiation oncologists agreed. CONCLUSION: This study demonstrates that although radiation oncologists and colorectal surgeons agreed on a majority of aspects such as diagnostic imaging, biomarker, systemic therapy, and optimal timing of OMD, they also had quite different perspectives on several aspects of OMD. Understanding these differences is crucial to achieving multidisciplinary consensus on the definition and optimal management of OMD.

Evaluating the Necessity of Adaptive RT and the Role of Deformable Image Registration in Lung Cancer with Different Pathologic Classifications.

BACKGROUND: This study aimed to analyze differential radiotherapy (RT) responses according to the pathological type of lung cancer to see the possibility of applying adaptive radiotherapy (ART). METHODS: ART planning with resampled-computed tomography was conducted for a total of 30 patients (20 non-small-cell lung cancer patients and 10 small-cell lung cancer patients) using a deformable image registration technique to reveal gross tumor volume (GTV) changes according to the duration of RT. RESULTS: The small-cell lung cancer group demonstrated an average GTV reduction of 20.95% after the first week of initial treatment (p = 0.001), whereas the adenocarcinoma and squamous cell carcinoma groups showed an average volume reduction of 20.47% (p = 0.015) and 12.68% in the second week. The application of ART according to the timing of GTV reduction has been shown to affect changes in radiation dose irradiated to normal tissues. This suggests that ART applications may have to be different depending on pathological differences in lung cancer. CONCLUSION: Through these results, the present study proposes the possibility of personalized treatment options for individual patients by individualizing ART based on specific radiation responses by pathologic types of lung cancer.

Effect of jaw size in megavoltage CT on image quality and dose.

PURPOSE: Recently, the jaw size for the TomoTherapy Hi-Art II(®) (TomoTherapy Inc., Madison, WI) was reduced from 4 mm (J4) to 1 mm (J1) to improve the longitudinal (IEC-Y) resolution in megavoltage computed tomography (MVCT) images. This study evaluated the effect of jaw size on the image quality and dose, as well as the dose delivered to the lens of the eye, which is a highly radiosensitive tissue. METHODS: MVCT image quality (image noise, uniformity, contrast linearity, high-contrast resolution, and full width at half-maximum) and multiple scan average dose (MSAD) were measured at different jaw sizes. A head phantom and photoluminescence glass dosimeters (PLDs) were used to measure the exposed lens dose (cGy). Different MVCT scan modes (pitch = 1, 2, and 3) and scan lengths (108 mm, 156 mm, and 204 mm) were applied in the MSAD and PLDs measurements. RESULTS: The change in jaw size from J4 to J1 produced no change or only a slight improvement in image noise, uniformity, contrast linearity, and high-contrast resolution. However, the full-width at half-maximum reduced from approximately 7.2 at J4 to 4.5 mm at J1, which represents an enhancement in the longitudinal resolution. The MSAD at the center point changed from approximately 0.69-2.32 cGy (peripheral: 0.83-2.49 cGy) at J4 to 0.85-2.81 cGy (peripheral: 1.05-2.86 cGy) at J1. The measured lens dose increased from 0.92-3.36 cGy at J4 to 1.06-3.91 cGy at J1. CONCLUSIONS: The change in jaw size improved longitudinal resolution. The MVCT imaging dose of approximately 3.86 cGy, 1.92 cGy, and 1.22 cGy was delivered at a pitch of 1, 2, and 3, respectively, per fraction in the head and neck treatment plans. Therefore, allowance for an approximately 15% increase in lens dose over that with J4 should be provided with J1.

Neutrophil to Lymphocyte Ratio and Platelet to Lymphocyte Ratio in Hepatocellular Carcinoma Treated with Stereotactic Body Radiotherapy.

Purpose: To investigate the prognostic value of the neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) in patients with hepatocellular carcinoma (HCC) treated with stereotactic body radiotherapy (SBRT). Methods: The medical records of HCC patients treated with SBRT between 2008 and 2019 were reviewed retrospectively. The NLR and PLR were calculated from the serum complete blood count before and after SBRT, and the prognostic values of the NLR and PLR for the treatment outcomes were evaluated. Results: Thirty-nine patients with 49 HCC lesions were included. After a median follow-up of 26.8 months (range, 8.4-80.0 months), three-year local control, overall survival (OS), and progression-free survival (PFS) rate were 97.4%, 78.3%, and 35.2%, respectively. Both NLR and PLR increased significantly after SBRT and decreased slowly to the pre-SBRT value at 6 months. Univariable analysis showed that gross tumor volume (GTV) >14 cc, post-SBRT PLR >90, and PLR change >30 were associated with a poorer OS (p=0.002, p=0.011, and p=0.001, respectively), and the PLR change was significant in multivariable analysis (hazard ratio [HR], 10.09; 95% CI, 1.15-88.40; p=0.037). For PFS, GTV >14 cc, post-SBRT NLR >2.5 and post-SBRT PLR >90 were predictive of a poorer PFS in univariable analysis (p=0.011, p=0.004 and p=0.041, respectively) and only post-SBRT NLR >2.5 remained significant in multivariable analysis (HR, 2.44; 95% CI, 1.03-5.76; p=0.042, respectively). Conclusions: The NLR and PLR increased transiently after SBRT, and the post-SBRT NLR and PLR were associated with the clinical outcomes of HCC patients.

Interobserver variability in clinical target volume delineation in anal squamous cell carcinoma.

We evaluated the inter-physician variability in the target contouring of the radiotherapy for anal squamous cell carcinoma (ASCC). Clinical target volume (CTV) of three patients diagnosed with ASCC was delineated by seven experienced radiation oncologists from multi-institution. These patients were staged as pT1N1a, cT2N0, and cT4N1a, respectively, according to 8th edition of the American Joint Committee on Cancer staging system. Expert agreement was quantified using an expectation maximization algorithm for Simultaneous Truth and Performance Level Estimation (STAPLE). The maximum distance from the boundaries of the STAPLE generated volume with confidence level of 80% to those of the contour of each CTV in 6 directions was compared. CTV of pelvis which includes primary tumor, perirectal tissue and internal/external iliac lymph node (LN) area (CTV-pelvis) and CTV of inguinal area (CTV-inguinal) were obtained from the seven radiation oncologists. One radiation oncologist did not contain inguinal LN area in the treatment target volume of patient 2 (cT2N0 stage). CTV-inguinal displayed moderate agreement for each patient (overall kappa 0.58, 0.54 and 0.6, respectively), whereas CTV-pelvis showed substantial agreement (overall kappa 0.66, 0.68 and 0.64, respectively). Largest variation among each contour was shown in the inferior margin of the CTV-inguinal. For CTV-pelvis, anterior and superior margin showed the biggest variation. Overall, moderate to substantial agreement was shown for CTV delineation. However, large variations in the anterior and cranial boarder of the CTV-pelvis and the caudal margin of the CTV-inguinal suggest that further studies are needed to establish a clearer target volume delineation guideline.

Neutrophil-to-Lymphocyte Ratio After Definitive Concurrent Chemoradiotherapy Predicts Survival in Patients With Esophageal Squamous Cell Carcinoma.

BACKGROUND/AIM: Lymphocyte-to-monocyte ratio, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio represent systemic immune-inflammatory responses. We evaluated the association between immune-inflammatory cell ratios and prognosis in esophageal squamous cell carcinoma (ESCC) patients who underwent definitive concurrent chemoradiotherapy (dCCRT). PATIENTS AND METHODS: Medical records of 68 ESCC patients in three institutions who underwent dCCRT between 2006 and 2017 were reviewed. The immune-inflammatory cell ratios were calculated before and after dCCRT. RESULTS: The median follow-up time was 11.4 months. The 3-year overall survival (OS) rate was 21.6%. Among the immune-inflammatory cell ratios, lower post-dCCRT neutrophil-to-lymphocyte ratio (NLRpost) was associated with better OS (median 15.2 vs. 9.7 months, p=0.030). Patients with lower NLRpost had more improved OS when adjuvant chemotherapy was administered following dCCRT (median 16.6 vs. 4.8 months, p<0.001). CONCLUSION: NLRpost may be useful in predicting OS in ESCC patients after dCCRT. Furthermore, NLRpost might play a role in establishing adjuvant therapy plans following dCCRT.

Clinical Outcome of Salvage Radiotherapy for Locoregional Clinical Recurrence After Radical Prostatectomy.

Objectives: To assess the clinical outcomes of prostate cancer patients treated with salvage radiotherapy (SRT) for locoregional clinical recurrence (CR) after radical prostatectomy (RP). Methods: Records of 60 patients with macroscopic locoregional recurrence after prostatectomy and referrals for SRT were retrospectively investigated in the multi-institutional database. The median radiation dose was 70.2 Gy. Biochemical failure was defined as the prostate-specific antigen (PSA) ≥ nadir + 2 or initiation of androgen deprivation therapy (ADT) for increased PSA. Results: Median recurrent tumor size was 1.1 cm and pre-radiotherapy PSA level was 0.4 ng/ml. At a median follow-up of 83.1-month after SRT, 7-year biochemical failure-free survival (BCFFS), locoregional failure-free survival (LRFFS), distant metastasis-free survival (DMFS), and overall survival (OS) were 67.0%, 89.7%, 83.6%, and 91.2%, respectively. Higher Gleason's scores were associated with unfavorable BCFFS, DMFS, and OS. Pre-SRT PSA ≥0.5 ng/ml predicted worse BCFFS, LRFFS, and DMFS. In multivariate analyses, a Gleason's score of 8 to 10 was associated with decreased BCFFS (hazard ratio [HR] 3.12, 95% confidence interval [CI] 1.11-8.74, P = .031) and OS (HR 17.72, 95% CI 1.75-179.64, P = .015), and combined ADT decreased the risks of distant metastasis (HR 0.18, 95% CI 0.04-0.92, P = .039). Two patients (3.3%) experienced late grade 3 urinary toxicity. Conclusions: SRT for locoregional CR after RP achieved favorable outcomes with acceptable long-term toxicities. Higher Gleason's scores and pre-radiotherapy PSA level were unfavorable prognostic variables. Combined ADT may decrease the risks of metastases.

Optimizing External Beam Radiotherapy as per the Risk Group of Localized Prostate Cancer: A Nationwide Multi-Institutional Study (KROG 18-15).

PURPOSE: This nationwide multi-institutional study analyzed the patterns of care and outcomes of external beam radiotherapy (EBRT) in localized prostate cancer patients. We compared various risk classification tools and assessed the need for refinements in current radiotherapy (RT) schemes. METHODS AND MATERIALS: We included non-metastatic prostate cancer patients treated with primary EBRT from 2001 to 2015 in this study. Data of 1573 patients from 17 institutions were analyzed and re-grouped using a risk stratification tool with the highest predictive power for biochemical failure-free survival (BCFFS). We evaluated BCFFS, overall survival (OS), and toxicity rates. RESULTS: With a median follow-up of 75 months, 5- and 10-year BCFFS rates were 82% and 60%, and 5- and 10-year OS rates were 95% and 83%, respectively. NCCN risk classification revealed the highest predictive power (AUC = 0.556, 95% CI 0.524-0.588; p < 0.001). Gleason score, iPSA < 12 ng/mL, intensity-modulated RT (IMRT), and ≥179 Gy1.5 (EQD2, 77 Gy) were independently significant for BCFFS (all p < 0.05). IMRT and ≥179 Gy1.5 were significant factors in the high-risk group, whereas ≥170 Gy1.5 (EQD2, 72 Gy) was significant in the intermediate-risk group and no significant impact of dose was observed in the low-risk group. Both BCFFS and OS improved significantly when ≥179 Gy1.5 was delivered using IMRT and hypofractionation in the high-risk group without increasing toxicities. CONCLUSIONS: With NCCN risk classification, dose escalation with modern high-precision techniques might increase survivals in the high-risk group, but not in the low-risk group, although mature results of prospective studies are awaited.

An international Delphi consensus for pelvic stereotactic ablative radiotherapy re-irradiation.

INTRODUCTION: Stereotactic Ablative Radiotherapy (SABR) is increasingly used to treat metastatic oligorecurrence and locoregional recurrences but limited evidence/guidance exists in the setting of pelvic re-irradiation. An international Delphi study was performed to develop statements to guide practice regarding patient selection, pre-treatment investigations, treatment planning, delivery and cumulative organs at risk (OARs) constraints. MATERIALS AND METHODS: Forty-one radiation oncologists were invited to participate in three online surveys. In Round 1, information and opinion was sought regarding participants' practice. Guidance statements were developed using this information and in Round 2 participants were asked to indicate their level of agreement with each statement. Consensus was defined as ≥75% agreement. In Round 3, any statements without consensus were re-presented unmodified, alongside a summary of comments from Round 2. RESULTS: Twenty-three radiation oncologists participated in Round 1 and, of these, 21 (91%) and 22 (96%) completed Rounds 2 and 3 respectively. Twenty-nine of 44 statements (66%) achieved consensus in Round 2. The remaining 15 statements (34%) did not achieve further consensus in Round 3. Consensus was achieved for 10 of 17 statements (59%) regarding patient selection/pre-treatment investigations; 12 of 13 statements (92%) concerning treatment planning and delivery; and 7 of 14 statements (50%) relating to OARs. Lack of agreement remained regarding the minimum time interval between irradiation courses, the number/size of pelvic lesions that can be treated and the most appropriate cumulative OAR constraints. CONCLUSIONS: This study has established consensus, where possible, in areas of patient selection, pre-treatment investigations, treatment planning and delivery for pelvic SABR re-irradiation for metastatic oligorecurrence and locoregional recurrences. Further research into this technique is required, especially regarding aspects of practice where consensus was not achieved.

Adjuvant Chemotherapy and Dose Escalation in Definitive Concurrent Chemoradiotherapy for Esophageal Squamous Cell Carcinoma.

BACKGROUND/AIM: To validate the effect of treatment intensification on survival in esophageal squamous cell carcinoma (ESCC) patients undergoing definitive concurrent chemoradiotherapy (dCCRT). PATIENTS AND METHODS: We reviewed the medical records of 73 ESCC patients who underwent dCCRT between 2006 and 2017 in 3 institutions. RESULTS: The median follow-up time was 13.3 months. The median overall survival (OS) and locoregional recurrence-free survival (LRFS) were 13.3 and 11.2 months, respectively. The median radiotherapy dose was 55.8 Gy, and the median biologically effective dose (BED) was 65.8 Gy. Chemotherapy was given in all patients during dCCRT, and adjuvant chemotherapy was administered in 56 patients (76.7%). Adjuvant chemotherapy improved OS (3-year, 24.2% vs. 11.8%, p=0.004). Higher BED ≥70 Gy improved LRFS (3-year, 41.7% vs. 23.6%, p=0.035). CONCLUSION: The addition of chemotherapy after dCCRT improves OS. A higher radiotherapy dose improved LRFS, but not OS. Adjuvant chemotherapy should be considered after dCCRT for better outcomes.

Post-operative radiation therapy with or without chemotherapy for anal squamous cell carcinoma incidentally discovered after local excision: a propensity score matched analysis of retrospective multicenter study.

OBJECTIVE: To evaluate the results of post-operative radiation therapy (RT) for anal squamous cell carcinoma (ASCC) incidentally detected after excision, and compare these outcomes with those of definitive RT without excision for exploring the possibility of treatment de-intensification. METHODS AND MATERIALS: A total of 25 patients with T1-2N0-1 ASCC who underwent RT following incidental tumor resection were selected from multicenter retrospective database. And, we selected one-to-one matched 25 patients receiving definitive RT from the same database using propensity score matching method, and the outcomes were compared. RESULTS: Median age was 60 years (range, 30-76), and 18 patients (72%) were female. 19 patients (76%) had T0/1 tumors and four patients (16%) had regional lymph node metastases. Hemorrhoidectomy was performed in eight patients (32%) and the others underwent local excision. 12 patients (48%) had microscopic or gross residual diseases. Median RT dose to the primary lesion was 50.4 Gy (range, 40-60). Concurrent chemotherapy was delivered to 23 patients (92%). Median follow-up period was 71 months (range, 4.5-203.1 months). None of the patients showed recurrence during follow-up. However, one patient died after 6 months due to the chemotherapy-related hematologic toxicity. When compared with those patients receiving definitive RT, clinicopathological variables were well-balanced between the two groups. While matched paired patients treated with definitive RT received a higher median RT dose of 54 Gy (range, 45-61.2) and concurrent chemotherapy was given to 22 patients (88%), overall survival was not significantly different (p = 0.262). CONCLUSION: Patients treated with RT for early stage ASCC after local excision showed favorable treatment outcomes. Further study is warranted to justify the de-intensification of the treatment for these patients. ADVANCES IN KNOWLEDGE: Post-operative RT can achieve favorable treatment outcomes in incidental ASCC with residual diseases after local excision.