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Katsuyuki Sakanaka,1 Kota Fujii,1 Yuichi Ishida,1 Shin’ichi Miyamoto,2 Takahiro Horimatsu,3 Manabu Muto,3 Takashi Mizowaki11Department of Radiation Oncology and Image-applied Therapy, Graduate School of Medicine, Kyoto University, Kyoto, Japan; 2Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan; 3Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University, Kyoto, JapanPurpose: Whether nutritional assessment and management improves clinical outcomes in patients with clinical T1N0M0 esophageal squamous cell carcinoma (ESCC) who undergo chemoradiotherapy remains to be demonstrated. This study aimed to determine the nutritional status of such patients pre- and post-chemoradiotherapy and its clinical outcomes.Patients and methods: This single institutional retrospective study included patients who underwent chemoradiotherapy for clinical T1N0M0 ESCC using serum albumin concentrations and body weights evaluated pre- and post-chemoradiotherapy from January 2005 to December 2016. The nutritional risk index (NRI) score was used to quantify the nutritional status: NRI score ≥100: no risk, 97.5–100: mild risk, 83.5–97.5: moderate risk, and

Background: Patients with esophageal squamous cell carcinoma (ESCC) with distant metastasis were treated with systemic chemotherapy. Recent advances in multimodal treatments have made conversion therapy a viable option for patients with incurable ESCC., Objective: We aimed to assess the safety and efficacy of conversion therapy for ESCC with distant metastases., Methods: Conversion therapy was defined as surgery or chemoradiotherapy (CRT) used to cure tumors that were previously considered incurable because of distant metastasis. We conducted a retrospective review of patients who underwent ESCC conversion therapy and assessed the treatment outcomes, including adverse events and survival rates., Results: A total of 147 patients from 22 institutions were included. Systemic chemotherapy was initially administered to all patients. The most common M1 factor was the para-aortic lymph node, accounting for 55% of cases. Following the initial treatment, 116 patients underwent surgery, with 31 receiving CRT as conversion therapy. Postoperative complications in surgery patients included pneumonia (16%), anastomotic leakage (7%), and recurrent laryngeal nerve palsy (6%). During CRT, 18% of patients developed grade 3 or higher non-hematological toxicities. The 5-year overall survival (OS) rate was 31.7%. Pathological responders had significantly longer OS than non-responders (hazard ratio 0.493, p = 0.012). The distribution of distant metastasis, regimen type, clinical response, and conversion therapy modality did not have a significant impact on OS., Conclusions: Conversion therapy can be safely performed for ESCC with distant metastasis and has a favorable prognosis., (© 2024. Society of Surgical Oncology.)

Acquired hemophilia A (AHA) is an acquired bleeding disorder caused by neutralizing antibodies (inhibitors) against Coagulation Factor VIII (FVIII:C), causing sudden hemorrhagic symptoms (i.e., subcutaneous bleeding, intramuscular bleeding, and hematuria). Herein, this study is aimed at presenting a case of AHA diagnosed based on hematuria and reviewing patients who were diagnosed with AHA due to hematuria. A 67-year-old woman was referred to Atsugi City Hospital with painless gross hematuria that began 4 weeks before presentation. Contrast-enhanced computed tomography (eCT) revealed an approximately 2 cm mass in the right renal pelvis, and the patient's activated partial thromboplastin time (APTT) was elevated (61.4 s). The day after the endoscopic biopsy, the patient was in shock due to a large retroperitoneal hematoma. Although her condition stabilized after intravenous radioembolization, she underwent emergency surgeries several times because of rebleeding within the next 3 weeks. At that time, APTT was more prolonged at 106.4 s, and the FVIII:C level was 2%. Mixing tests showed an upwardly convex curve after 2-h incubation, indicating the presence of an inhibitor. Factor VIII inhibitor titer was ≥5.1 Bethesda unit (BU)/mL. A combined product of Plasma-Derived Factors VIIa and X (pd-FVIIa/FX), as second-line hemostatic therapy, as well as cyclophosphamide (CYP), were administered after Recombinant Activated Factor VIIa (rFVIIa) had been ineffective. Following this, the Factor VIII inhibitor titer was undetectable, FVIII:C levels were restored, and APTT decreased to within the normal range. Gross hematuria was significantly alleviated. However, the patient died of cytomegalovirus and fungal infections due to prolonged immunosuppressive therapy. Although AHA diagnosed based on hematuria may have a better prognosis than others, there have been occasional cases with severe outcomes. APTT, detected upon initial hematological testing in patients with hematuria, may be a potential indicator of an existing AHA., Competing Interests: Takahiro Kimura is a paid consultant/advisor of Astellas, Bayer, Janssen, and Sanofi. The other authors declare no conflicts of interest., (Copyright © 2024 Kenichi Hata et al.)

Approximately 90% of esophageal cancers in Japan are squamous cell carcinomas, and they are often detected at earlier stages in Japan than in Western countries; superficial esophageal cancer without lymph node or distant metastasis comprises one-third of all esophageal cancers in Japan. Endoscopic resection is a minimally invasive treatment for superficial esophageal cancer; however, the risk of regional lymph node recurrence is negligible when it invades the submucosal layer or lymphovasculature. In such cases, surgical treatment is necessary to control regional lymph node recurrences, although the physical burdens and potential complications cannot be overlooked. Recently, clinical trials in Japan have shown promising clinical outcomes of organ preservation strategies. One strategy is initially performing endoscopic resection for superficial esophageal cancer, assessing the risk of lymph node metastasis based on pathological diagnosis for endoscopically resected specimens, and subsequently considering additional therapy (e.g., observation or prophylactic chemoradiotherapy)-another strategy aimed to cure superficial esophageal cancer through definitive chemoradiotherapy alone. The safety and efficacy of the two strategies have been evaluated in clinical trials, which showed that both organ preservation strategies are comparable to surgery in terms of overall survival. However, challenges include improving the accuracy of pretreatment endoscopic diagnosis and decreasing the local-regional recurrence after chemoradiotherapy. This review provides an overview of the latest standard treatment for early-stage esophageal cancer and its future perspectives., (© 2024. The Author(s).)

Background: There is sparse evidence regarding optimal management and prognosticators for oncologic outcomes in patients with clinical node-positive (cN+) upper tract urothelial carcinoma (UTUC)., Methods: We retrospectively analyzed the data from 105 UTUC patients with cN1-2M0 between June 2010 and June 2022 at multiple institutions affiliated with our university. At the time of diagnosis, all patients received standard-of-care treatment including radical nephroureterectomy (RNU), chemotherapy, and/or palliative care. We employed a Cox regression model to analyze the prognostic importance of various factors on overall survival (OS)., Results: Of 105 patients, 54 (51%) underwent RNU, while 51 (49%) did not. RNU was likely to be selected in patients with younger and higher G8 score, resulting in better median OS in patients who underwent RNU than in those who did not (42 months vs. 15 months, p < 0.001). Multivariable analysis among the entire cohort revealed that low G8 score (≤14) (hazard ratio [HR]: 2.07, 95% confidence interval [CI]: 1.08-3.99), elevated pretreatment C-reactive protein (CRP) (HR: 3.35, 95%CI: 1.63-6.90), and failure to perform RNU (HR: 2.16, 95%CI: 1.06-4.42) were independent prognostic factors for worse OS. In the subgroup analyses of cohorts who did not undergo RNU, elevated pretreatment CRP was the only independent prognostic factor for worse OS in cN+ UTUC patients., Conclusions: RNU seems to be a reasonable treatment option in cN+ UTUC patients where applicable. Elevated pretreatment CRP appears to be a reliable prognosticator of worse OS and may be helpful in optimizing candidate selection for intensified treatment in this setting., (© 2024 The Japanese Urological Association.)

Background: An earlier systematic review and meta-analysis found that patients with a certain histological variant of upper tract urothelial carcinoma (UTUC) exhibited more advanced disease and poorer survival than those with pure UTUC. A difference in the clinicopathological UTUC characteristics of Caucasian and Japanese patients has been reported, but few studies have investigated the clinical impact of the variant histology in Japanese UTUC patients., Methods: We retrospectively enrolled 824 Japanese patients with pTa-4N0-1M0 UTUCs who underwent radical nephroureterectomy without neoadjuvant chemotherapy. Subsequently, we explored the effects of the variant histology on disease aggressiveness and the oncological outcomes. We used Cox's proportional hazards models to identify significant predictors of oncological outcomes, specifically intravesical recurrence-free survival (IVRFS), recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS)., Results: Of the 824 UTUC patients, 32 (3.9%) exhibited a variant histology that correlated significantly with a higher pathological T stage and lymphovascular invasion (LVI). Univariate analysis revealed that the variant histology was an independent risk factor for suboptimal RFS, CSS, and OS. However, significance was lost on multivariate analyses., Conclusions: The variant histology does not add to the prognostic information imparted by the pathological findings after radical nephroureterectomy, particularly in Japanese UTUC patients., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tau.amegroups.com/article/view/10.21037/tau-23-561/coif). The authors have no conflicts of interest to declare., (2024 Translational Andrology and Urology. All rights reserved.)

Patients after renal transplantation are susceptible to secondary malignancies, including anal squamous cell carcinoma. Chemoradiotherapy is the standard treatment for anal squamous cell carcinoma; however, typical irradiation fields for anal cancer encompass a transplanted kidney located in the right iliac fossa, which causes complete renal dysfunction. Thus, typical irradiation fields are not feasible for this population. Additionally, standard concurrent chemotherapy demonstrates nephrotoxicity. Here, we report a case of modified definitive chemoradiotherapy for a 40-year-old patient with locally advanced perianal squamous cell carcinoma after renal transplantation whose abdominoperineal resection was difficult because of a history of repeated open surgeries and long-term steroids. We modified the cranial side of the elective nodal irradiation fields in this case to spare the transplanted kidney, considering the lymph chains of the perianal tumor. We then used continuous 5-fluorouracil to avoid nephrotoxicity of mitomycin C, considering his life expectancy. Modified definitive chemoradiotherapy achieved complete remission with expected toxicities. Now, approximately five years after the procedure, the patient remains disease-free, preserving anal and renal function. Definitive chemoradiotherapy using modified irradiation fields and chemotherapy may be an option for patients with anal squamous cell carcinoma after renal transplantation., Competing Interests: Conflict of interestThe authors declare no conflicts of interest., (© The Author(s) under exclusive licence to The Japan Society of Clinical Oncology 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Objective: The population with pathological T3 (pT3) upper tract urothelial carcinoma (UTUC) is heterogeneous, thereby making prognostication challenging. We assessed the clinical ramifications of subclassifying pT3 UTUC after nephroureterectomy., Methods: We conducted a retrospective analysis including 308 patients who underwent nephroureterectomy for pT3N0-1M0 UTUC. pT3 was subclassified into pT3a and pT3b based on invasion of the peripelvic and/or periureteral fat. Cox's proportional hazard models were utilized to determine the significant prognosticators of oncological outcomes, encompassing intravesical recurrence-free survival, recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival., Results: Multivariate analysis elucidated that pT3b status, pathological N1 status, and lymphovascular invasion status were independent risk factors for an unfavorable RFS and CSS. Although the RFS and CSS of patients with pT3b UTUC were superior to those in patients with pT4 UTUC, no significant disparities were detected between patients with pT3a and pT2., Conclusion: Our findings demonstrate that pT3 UTUC with peripelvic/periureteral fat invasion is independently associated with metastasis and cancer-specific death after nephroureterectomy. These findings provide patients and physicians with invaluable insight into the risk for disease progression in pT3 UTUC patients., (© 2023 The Japanese Urological Association.)

Chemoradiotherapy has been considered as one of the standard treatment options for clinical T1bN0M0 esophageal squamous cell carcinoma with organ preservation. However, 20% of patients develop locoregional recurrence after chemoradiotherapy, which requires salvage treatment including salvage surgery and endoscopic resection. Salvage surgery can cause complications and treatment-related death. Interestingly, chemoradiotherapy with elective nodal irradiation has been reported to reduce the locoregional recurrence of advanced esophageal squamous cell carcinoma. Hence, we are conducting a clinical trial to confirm whether modified chemoradiotherapy with elective nodal irradiation was superiority to that without elective nodal irradiation for the patients with cT1bN0M0 esophageal squamous cell carcinoma. The primary endpoint is major progression-free survival, defined as the time from randomization to the date of death or disease progression, excluding successful curative resection through salvage endoscopic resection. We plan to enroll 280 patients from 54 institutions over 4 years. This trial has been registered in the Japan Registry of Clinical Trials (jRCTs031200067)., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Recent clinical trials have reported improved disease-free survival rates of patients with stage pT3-4/ypT2-4 or pN + upper tract urothelial carcinoma (UTUC) on adjuvant nivolumab therapy. However, the appropriateness of the patient selection criteria used in clinical practice remains uncertain., Methods: We retrospectively analyzed 895 patients who underwent nephroureterectomy to treat UTUC. The patients were divided into two groups: grade pT3-4 and/or pN + without neoadjuvant chemotherapy (NAC) or grade ypT2-4 and/or ypN + on NAC (adjuvant immunotherapy candidates) and others (not candidates for adjuvant immunotherapy). Kaplan-Meier curves were drawn to assess the oncological outcomes, including recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS). Cox proportional hazards models were used to identify significant prognostic factors for oncological outcomes., Results: The Kaplan-Meier curves revealed notably inferior RFS, CSS, and OS of patients who were candidates for adjuvant immunotherapy. Multivariate analysis revealed that pathological T and N grade and lymphovascular invasion (LVI) status were independent risk factors for poor RFS, CSS, and OS., Conclusion: In total, 44.8% of patients were candidates for adjuvant immunotherapy. In addition to pathological T and N status, LVI was a significant predictor of survival, and may thus play a pivotal role in the selection of patients eligible for adjuvant immunotherapy., (© 2023. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Background: Multiple studies have demonstrated the effectiveness of neoadjuvant chemotherapy and adjuvant chemotherapy in patients with upper tract urothelial carcinoma compared with surgery alone. However, no clinical trial has established the superiority of neoadjuvant chemotherapy or adjuvant chemotherapy in terms of perioperative outcomes., Methods: We conducted a retrospective analysis encompassing 164 upper tract urothelial carcinoma patients who underwent radical nephroureterectomy and received perioperative chemotherapy. Of these patients, 65 (39.6%) and 99 (60.4%) received neoadjuvant chemotherapy and adjuvant chemotherapy, respectively. Recurrence-free survival and cancer-specific survival were computed using the Kaplan-Meier method. Additionally, we conducted Cox regression analyses to evaluate the risk factors for recurrence-free survival and cancer-specific survival., Results: Pathological downstaging was seen in 37% of the neoadjuvant chemotherapy group. However, no pathological complete response was observed in this cohort. The Kaplan-Meier curves demonstrated significantly lower recurrence-free survival and cancer-specific survival in patients who received adjuvant chemotherapy. Multivariate Cox regression analysis revealed patients treated with adjuvant chemotherapy exhibited a marked association with inferior recurrence-free survival and cancer-specific survival., Conclusion: Our study has suggested that neoadjuvant chemotherapy would be more effective in high-risk upper tract urothelial carcinoma patients compared with adjuvant chemotherapy., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The role of adjuvant external-beam radiotherapy (EBRT) for locally advanced differentiated thyroid cancer (DTC) is controversial because of the lack of prospective data. To prepare for a clinical trial, this study investigated the current clinical practice of adjuvant treatments for locally advanced DTC. A survey on treatment selection criteria for hypothetical locally advanced DTC was administered to representative thyroid surgeons of facilities participating in the Japan Clinical Oncology Group Radiation Therapy Study Group. Of the 43 invited facilities, surgeons from 39 (91%) completed the survey. For R1 resection or suspected residual disease, 26 (67%) facilities administered high-dose (100-200 mCi) radioactive iodine (RAI), but none performed EBRT. For R2 resection or unresectable primary disease, 26 (67%) facilities administered high-dose RAI and 7 (18%) performed adjuvant treatments, including EBRT. For complete resection with nodal extra-capsular extension, 13 (34%) facilities administered high-dose RAI and 1 (3%) performed EBRT. For unresectable mediastinal lymph node metastasis, 31 (79%) facilities administered high-dose RAI and 5 (13%) performed adjuvant treatments, including EBRT. Adjuvant EBRT was not routinely performed mainly because of the lack of evidence for efficacy (74%). Approximately 15% of the facilities routinely considered adjuvant EBRT for DTC with R2 resection or unresectable primary or lymph node metastasis disease. Future clinical trials will need to optimize EBRT for these patients.

Purpose: The aim of this study was to investigate the oncologic efficacy of combining docetaxel with androgen deprivation therapy (ADT) versus nonsteroidal antiandrogen (NSAA) with ADT in patients with high-volume metastatic hormone-sensitive prostate cancer (mHSPC) with focus on the effect of sequential therapy in a real-world clinical practice setting., Methods: The records of 382 patients who harbored high-volume mHSPC, based on the CHAARTED criteria, and had received ADT with either docetaxel (n = 92) or NSAA (bicalutamide) (n = 290) were retrospectively analyzed. The cohorts were matched by one-to-one propensity scores based on patient demographics. Overall survival (OS), cancer-specific survival (CSS), progression-free survival (PFS), including time to castration-resistant prostate cancer (CRPC), and time to second-line progression (PFS2) were compared. 2nd-line PFS defined as the time from CRPC diagnosis to progression after second-line therapy was also compared., Results: After matching, a total of 170 patients were retained: 85 patients treated with docetaxel + ADT and 85 patients treated with NSAA + ADT. The median OS and CSS for docetaxel + ADT versus NSAA + ADT were not reached (NR) vs. 49 months (p = 0.02) and NR vs. 55 months (p = 0.02), respectively. Median time to CRPC and PFS2 in patients treated with docetaxel + ADT was significantly longer compared to those treated with NSAA (22 vs. 12 months; p = 0.003 and, NR vs. 28 months; p < 0.001, respectively). There was no significant difference in 2nd-line PFS between the two groups., Conclusions: Our analysis suggested that ADT with docetaxel significantly prolonged OS and CSS owing to a better time to CRPC and PFS2 in comparison to NSAA + ADT in high-volume mHSPC., (© 2022. The Author(s).)

Background: We aimed to assess the clinical, oncological, and pathological impact of en bloc resection of bladder tumors (ERBT) compared with conventional transurethral resection of bladder tumors (cTURBT) for pT1 high-grade (HG) bladder cancer., Patients and Methods: We retrospectively analyzed the record of 326 patients (cTURBT: n = 216, ERBT: n = 110) diagnosed with pT1 HG bladder cancer at multiple institutions. The cohorts were matched by one-to-one propensity scores based on patient and tumor demographics. Recurrence-free survival (RFS), progression-free survival (PFS), cancer-specific survival (CSS), and perioperative and pathologic outcomes were compared. The prognosticators of RFS and PFS were analyzed using the Cox proportional hazard model., Results: After matching, 202 patients (cTURBT: n = 101, ERBT: n = 101) were retained. There were no differences in perioperative outcomes between the two procedures. The 3-year RFS, PFS, and CSS were not different between the two procedures (p = 0.7, 1, and 0.7, respectively). Among patients who underwent repeat transurethral resection (reTUR), the rate of any residue on reTUR was significantly lower in the ERBT group (cTURBT: 36% versus ERBT: 15%, p = 0.029). Adequate sampling of muscularis propria (83% versus 93%, p = 0.029) and diagnostic rates of pT1a/b substaging (90% versus 100%, p < 0.001) were significantly better in ERBT specimen compared with cTURBT specimen. On multivariable analyses, pT1a/b substaging was a prognosticator of disease progression., Conclusions: In patients with pT1HG bladder cancer, ERBT had similar perioperative and mid-term oncologic outcomes compared with cTURBT. However, ERBT improves the quality of resection and specimen, yielding less residue on reTUR and yielding superior histopathologic information such as substaging., (© 2023. Society of Surgical Oncology.)

Background/aim: Degarelix has been widely used for prostate cancer; however, injection site reactions (ISRs) can be a clinical issue. We assessed differences in ISR intensity and patient quality of life (QOL) between degarelix 80 mg and 480 mg, a three-month formulation launched in 2020 in Japan., Patients and Methods: We prospectively analyzed 25 patients with advanced prostate cancer. ISR intensity and patient QOL were evaluated before and after switching from degarelix 80 mg to 480 mg. A visual analogue scale (VAS) and faces rating scale (FRS) were applied to assess the ISRs. We applied a rating format from the M. D. Anderson Symptom Inventory (MDASI) to assess patient QOL., Results: For degarelix 80 mg and a first dose of 480 mg, the incidence rate of ISRs was 84% and 92%, respectively (p=0.083). ISR pain on the third day after injection scored by VAS was 2.7±2.8 and 5.2±2.7, respectively (p<0.001). Other ISR findings such as redness, induration, swelling, warmth, and itching were significantly worse for degarelix 480 mg than for 80 mg. In the category of patient QOL, interference with activities of daily living such as general activity was significantly worse after degarelix 480 mg (p=0.003). However, 80% of patients were able to continue degarelix 480 mg during the nine months of follow-up., Conclusion: Degarelix 480 mg seems to exacerbate pain and other ISR findings, and to reduce patient QOL, compared with degarelix 80 mg. Optimal management of ISRs is essential to maintain patient QOL when using degarelix 480 mg., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: Definitive chemoradiotherapy (CRT) is the standard treatment for patients with locally advanced esophageal cancer (EC) who refuse surgery as the initial therapy. However, poor survival, a high incidence of late toxicities, and severe complications after salvage surgery remain issues to be resolved. This single-arm multicenter trial (JCOG0909) aimed to confirm the efficacy of CRT modifications, including salvage treatment for reducing CRT-related toxicities and facilitating salvage treatment for improved survival., Methods and Materials: Patients with clinical stage II/III EC (International Union Against Cancer sixth edition, non-T4) were eligible. Chemotherapy comprised cisplatin (75 mg/m 2 on days 1 and 29) and 5-fluorouracil (1000 mg/m 2 /d on days 1-4 and 29-32). Radiation therapy was administered at a total dose of 50.4 Gy. Good responders received 1 to 2 additional cycles of chemotherapy. For residual or recurrent disease, salvage endoscopic resection or salvage surgery was performed based on specific criteria. The primary endpoint was 3-year overall survival (OS). The calculated sample size was 95 patients, with a 1-sided alpha of 5% and a power of 80%. The expected and threshold 3-year OS were 55% and 42%, respectively., Results: Overall, 96 patients were enrolled, and 94 were included in the efficacy analysis. A complete response was achieved in 55 patients (59%). Salvage endoscopic resection and salvage surgery were performed in 5 (5%) and 25 patients (27%), respectively. R0 resection by salvage surgery was achieved in 19 patients (76%). Five patients (20%) showed grade 3 or 4 early operative complications, and 9 patients (9.6%) showed grade 3 late toxicities during the long-term follow-up. The 3-year OS was 74.2% (90% confidence interval, 65.9%-80.8%)., Conclusion: The combination of definitive CRT and salvage treatment has lower CRT-related toxicities and yields good OS, thus making it a promising novel treatment option for patients with locally advanced EC., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The lung volume receiving low-dose irradiation has been reported to increase in volumetric-modulated arc radiotherapy (VMAT) compared with three-dimensional conformal radiotherapy (3DCRT) for thoracic esophageal cancer, which raises concerns regarding radiation pneumonitis (RP) risk. This single institutional retrospective cohort study aimed to explore whether VMAT for thoracic esophageal cancer was associated with RP. Our study included 161 patients with thoracic esophageal cancer, of whom 142 were definitively treated with 3DCRT and 39 were treated with VMAT between 2008 and 2018. Radiotherapy details, dose-volume metrics, reported RP risk factors and RP incidence were collected. The RP risk factors were assessed via multivariate analysis. Dose-volume analysis showed that VMAT delivered more conformal dose distributions to the target volume (P < 0.001) and reduced V30 Gy of heart (57% vs 41%, P < 0.001) but increased V5 Gy (54% vs 41%, P < 0.001) and V20 Gy (20% vs 17%, P = 0.01) of lungs compared with 3DCRT. However, the 1-year incidence rates of RP did not differ between the two techniques (11.3% in 3DCRT vs 7.7% in VMAT, P = 0.53). The multivariate analysis suggested that the presence of interstitial lung disease (ILD) (P = 0.01) and V20 Gy of lungs ≥20% (P = 0.008) were associated with RP. Conclusively, VMAT increased the lung volume receiving low to middle doses irradiation, although this might not be associated with RP. Further studies are needed to investigate the effect of using VMAT for delivering conformal dose distributions on RP., (© The Author(s) 2022. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

The irradiated volume of intestines is associated with gastrointestinal toxicity in preoperative chemoradiotherapy for rectal cancer. The current trial prospectively explored how much of the irradiated volume of intestines was reduced by intensity-modulated radiotherapy (IMRT) compared with 3-dimensional conformal radiotherapy (3DCRT) and whether IMRT might alleviate the acute gastrointestinal toxicity in this population. The treatment protocol encompassed preoperative chemoradiotherapy using IMRT plus surgery for patients with clinical T3-4, N0-2 low rectal cancer. IMRT delivered 45 Gy per 25 fractions for gross tumors, mesorectal and lateral lymph nodal regions, and tried to reduce the volume of intestines receiving 15 Gy (V15 Gy) < 120 cc and V45 Gy ≤ 0 cc, respectively, while keeping target coverage. S-1 and irinotecan were concurrently administered. Acute gastrointestinal toxicity, rates of clinical downstaging, sphincter preservation, local regional control (LRC) and overall survival (OS) were evaluated. Twelve enrolled patients completed the chemoradiotherapy protocol. The volumes of intestines receiving medium to high doses were reduced by the current IMRT protocol compared to 3DCRT; however, the predefined constraint of V15 Gy was met only in three patients. The rate of ≥ grade 2 gastrointestinal toxicity excluding anorectal symptoms was 17%. The rates of clinical downstaging, sphincter preservation, three-year LRC and OS were 75%, 92%, 92% and 92%, respectively. In conclusion, preoperative chemoradiotherapy using IMRT for this population might alleviate acute gastrointestinal toxicity, achieving high LRC and sphincter preservation; although further advancement is required to reduce the irradiated volume of intestines, especially those receiving low doses., (© The Author(s) 2021. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

Background: Although prostate cancer is a very common form of malignancy in men, the clinical significance of androgen deprivation therapy (ADT) with abiraterone acetate versus the nonsteroidal antiandrogen bicalutamide has not yet been verified in patients with high-risk metastatic hormone-sensitive prostate cancer (mHSPC). The present study was designed to initiate this verification in real-world Japanese clinical practice., Methods: We retrospectively analyzed the records of 312 patients with high-risk mHSPC based on LATITUDE criteria and had received ADT with bicalutamide (n = 212) or abiraterone acetate (n = 100) between September 2015 and December 2020. Bicalutamide was given at 80 mg daily and abiraterone was given at 1000 mg daily as four 250-mg tablets plus prednisolone (5-10 mg daily). Overall survival (OS), cancer-specific survival (CSS), and time to castration-resistant prostate cancer (CRPC) were compared. The prognostic factor for time to CRPC was analyzed by Cox proportional hazard model., Results: Patients in the bicalutamide group were older, and more of them had poor performance status (≧2), than in the abiraterone group. Impaired liver function was noted in 2% of the bicalutamide group and 16% of the abiraterone group (p < 0.001). Median follow-up was 22.5 months for bicalutamide and 17 months for abiraterone (p < 0.001). Two-year OS and CSS for bicalutamide versus abiraterone was 77.8% versus 79.5% (p = 0.793) and 81.1% versus 82.5% (p = 0.698), respectively. Median time to CRPC was significantly longer in the abiraterone group than in the bicalutamide group (NA vs. 13 months, p < 0.001). In multivariate analysis, Gleason score ≧9, high alkaline phosphatase, high lactate dehydrogenase, liver metastasis, and bicalutamide were independent prognostic risk factors for time to CRPC. Abiraterone prolonged the time to CRPC in patients with each of these prognostic factors., Conclusions: Despite limitations regarding the time-dependent bias, ADT with abiraterone acetate significantly prolonged the time to CRPC compared to bicalutamide in patients with high-risk mHSPC. However, further study with longer follow-up is needed., (© 2021 Wiley Periodicals LLC.)

Purpose: The primary advantage of en bloc resection of bladder tumors is to provide better diagnostic accuracy. However, the clinical significance of horizontal and vertical margin has not been demonstrated. We evaluated the clinical importance of surgical margins in patients who underwent en bloc resection of bladder tumors., Materials and Methods: We retrospectively analyzed the records of 140 consecutive patients who underwent en bloc resection of bladder tumors for nonmuscle invasive bladder cancer. We analyzed perioperative and oncological outcome, and compared patient demographics and recurrence-free survival for horizontal findings. The relationship between surgical margin and second transurethral resection outcome in pT1 bladder cancer was also analyzed., Results: Mean tumor diameter was 17.2±9.8 mm. Pathological stages were 93 cases in pTa and 47 cases in pT1. Diagnostic rates for the horizontal and vertical margins were 63% and 99%, respectively. The rates of sessile, carcinoma in situ, high grade, and pT1 tumors were significantly higher in the horizontal margin positive group (41) than in the negative group (47). There was no significant difference in 2-year recurrence-free survival based on horizontal margin findings (negative: 72.4%, positive: 75.4%, p=0.87). A second transurethral resection was performed in 31 of the 47 pT1 patients; pT1 residue was seen only in vertical margin positive cases, and 5 pTa/pTis residues at the transurethral resection scar were seen in 15 horizontal margin positive patients., Conclusions: Horizontal margin positive findings were not associated with recurrence-free survival, but careful assessment is warranted regarding residue at the original site. A second transurethral resection should be considered in patients with horizontal and vertical margin positive pT1 bladder cancer.

Purpose: This study aimed to assess dosimetric indices of RapidPlan model-based plans for different energies (6, 8, 10, and 15 MV; 6- and 10-MV flattening filter-free), multileaf collimator (MLC) types (Millennium 120, High Definition 120, dual-layer MLC), and disease sites (head and neck, pancreatic, and rectal cancer) and compare these parameters with those of clinical plans., Methods: RapidPlan models in the Eclipse version 15.6 were used with the data of 28, 42, and 20 patients with head and neck, pancreatic, and rectal cancer, respectively. RapidPlan models of head and neck, pancreatic, and rectal cancer were created for TrueBeam STx (High Definition 120) with 6 MV, TrueBeam STx with 10-MV flattening filter-free, and Clinac iX (Millennium 120) with 15 MV, respectively. The models were used to create volumetric-modulated arc therapy plans for a 10-patient test dataset using all energy and MLC types at all disease sites. The Holm test was used to compare multiple dosimetric indices in different treatment machines and energy types., Results: The dosimetric indices for planning target volume and organs at risk in RapidPlan model-based plans were comparable to those in the clinical plan. Furthermore, no dose difference was observed among the RapidPlan models. The variability among RapidPlan models was consistent regardless of the treatment machines, MLC types, and energy., Conclusions: Dosimetric indices of RapidPlan model-based plans appear to be comparable to the ones based on clinical plans regardless of energies, MLC types, and disease sites. The results suggest that the RapidPlan model can generate treatment plans independent of the type of treatment machine., (© 2021 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

Objective: Additional surgery is considered for patients at high risk for lymph node metastasis (LNM) after local resection for early rectal cancer. Several factors are considered as indications for additional surgery, although there are currently no definitive criteria. This study aimed to clarify the need for additional surgery based on the number of risk factors for LNM and to evaluate the significance of submucosal invasion on recurrence., Methods: Patients with early rectal cancer harboring risk factors for LNM who underwent local resection between March 2005 and December 2016 were retrospectively analyzed. Associations among the number of risk factors, prognosis, and additional treatment after local resection were investigated., Results: A total of 29 eligible patients were classified into the surgery (n = 10), chemoradiotherapy (n = 7), and no-additional-treatment (NAT, n = 12) groups. Among the 29 patients, 15 patients (52%) with only one risk factor did not relapse. The NAT group harbored fewer risk factors for LNM, and 8 of the 12 patients (67%) had only deep submucosal invasion. Local recurrence occurred in one patient in the chemoradiotherapy group. The estimated 5-year overall survival rates were 88.9%, 75.0%, and 81.5% in the surgery, chemoradiotherapy, and NAT groups, respectively. There were no disease-specific deaths in the overall cohort., Conclusions: In the present study, no recurrence occurred in patients who did not receive additional surgery with deep submucosal invasion as the only risk factor. A multicenter investigation is necessary to confirm the safety of nonsurgical options., Competing Interests: Conflicts of Interest There are no conflicts of interest., (Copyright © 2020 by The Japan Society of Coloproctology.)

Importance: The association of chemoradiotherapy (CRT) with a thoracic vertebral fracture in patients with esophageal cancer is unknown., Objective: To determine whether CRT is associated with thoracic vertebral fractures in patients with esophageal cancer., Design, Setting, and Participants: This retrospective cohort study included patients with clinical stages I to III thoracic esophageal cancer who visited the Kyoto University Hospital, Kyoto, Japan, from January 1, 2007, to December 31, 2013. Data were analyzed from April 6, 2018, to June 4, 2020., Exposures: Chemoradiotherapy (CRT group) or surgery or endoscopic treatment (non-CRT group)., Main Outcomes and Measures: The main outcome of this study was the cumulative incidence rate of thoracic vertebral fractures in 36 months. The incidence rate was calculated taking censoring into account. Possible risk factors, including CRT, were explored in the multivariable analysis. The association of irradiated doses with fractured vertebrae was also evaluated., Results: A total of 315 patients (119 for the CRT group and 196 for the non-CRT group) were included. The median age of patients was 65 (range, 32-85) years. Fifty-six patients (17.8%) were female and 259 (82.2%) were male. The median observation time was 40.4 (range, 0.7-124.1) months. Thoracic vertebral fractures were observed in 20 patients (16.8%) in the CRT group and 8 patients (4.1%) in the non-CRT group. The 36-month incidence rate of thoracic vertebral fractures was 12.3% (95% CI, 7.0%-19.1%) in the CRT group and 3.5% (95% CI, 1.3%-7.5%) in the non-CRT group (hazard ratio [HR], 3.41 [95% CI, 1.50-7.73]; P = .003). The multivariable analysis showed that the HR of the thoracic vertebral fracture in the CRT group to non-CRT group was 3.91 (95% CI, 1.66-9.23; P = .002) with adjusting for sex, 3.14 (95% CI, 1.37-7.19; P = .007) with adjusting for age, and 3.10 (95% CI, 1.33-7.24; P = .009) with adjusting for the history of vertebral or hip fractures. The HR of the thoracic vertebral fracture for a 5-Gy increase in the mean radiation dose to the single vertebra was 1.19 (95% CI, 1.04-1.36; P = .009)., Conclusions and Relevance: This study found that chemoradiotherapy was associated with thoracic vertebral fractures in patients with esophageal cancers. A reduced radiation dose to thoracic vertebrae may decrease the incidence of fractures.

Purpose: Among various therapeutic options available for metastatic castration-resistant prostate cancer (mCRPC), only apalutamide and enzalutamide have shown evidences of improved metastasis-free survival (MFS) for non-metastatic castration-resistant prostate cancer (nmCRPC). However, there is a paucity of evidence to indicate who may be targeted for aggressive therapy among patients with nmCRPC. The objectives of this retrospective study were to explore predictors of metastasis in patients with nmCRPC and to identify a subpopulation of patients with nmCRPC who may benefit from aggressive therapy., Methods: A total of 115 patients with CRPC who had no metastasis detected at the time of diagnosis of CRPC were included in this retrospective study. All patients were treated at Jikei University and its affiliated hospitals. The primary outcome measure was MFS from the time of diagnosis of CRPC. Predictors of MFS were also explored with a multivariate Cox hazard model., Results: The median observation period after diagnosis of CRPC was 30 months (range 2-143 months). Kaplan-Meier analysis revealed a median MFS of 76. Multivariate analysis demonstrated that low alkaline phosphatase (ALP) values at diagnosis of CRPC and favorable response to primary androgen deprivation therapy (ADT) were significant predictors of longer MFS (P = 0.011, and 0.031, respectively)., Conclusions: Results of this study suggest that high ALP values at diagnosis of CRPC and poor response to primary ADT may predict the propensity of metastasis in patients with nmCRPC. Further prospective studies will be required enrolling more patients to confirm our findings.

Background: Although endoscopic resection is increasingly performed to treat submucosal invasive colorectal cancer (T1CRC), approximately 10% are at risk of lymph node metastasis. The Japanese Society for Cancer of the Colon and Rectum guideline indicates that the following risk factors should be considered when deciding whether to perform additional surgical resection with lymph node dissection: depth of T1 invasion, lymphovascular invasion, poor histological grade, and budding grade 2/3. However, there is little information about the prognosis of T1CRC patients, or factors to consider when deciding subsequent treatment of high-risk T1CRC., Methods: This retrospective mixed method study was conducted using electronic medical records at Kyoto University Hospital between February 2005 and February 2015. Participants were T1CRC patients at risk of lymph node metastasis with at least one of the above four risk factors. They were assigned either careful follow-up (FU) or additional surgery (AS) through shared decision-making. To identify factors affecting decision-making in the FU group, we performed qualitative content analysis of electronic medical records. The prognosis of the groups was compared using the Kaplan-Meier method and the log-rank test., Results: Of 161 T1CRC patients, 18 were included in the FU group and 19 in the AS group. The median follow-up time was 39.5 (range 23-126) months for the FU group and 62 (range 22-141) months for the AS group. Factors considered in selecting FU were advanced age, comorbidities, the sole presence of the "depth" risk factor, and lower rectal cancer. For AS, the risk factors cited in the guideline were considered. There was one recurrent case in each group during the research period. There were no significant differences in overall survival, cause-specific survival, or recurrence-free survival between the groups., Conclusions: Age, comorbidities, and lower-rectal cancer location were considered in deciding posttreatment strategy among high-risk T1CRC patients, alongside with positive vertical margin, depth, lymphovascular invasion, poor histologic grade, and budding. During the research period, there was no prognostic difference between the FU and AS groups.

Background: To the best of our knowledge, no study has reported mediastinal shift accompanied with obstructive atelectasis due to bulky primary esophageal tumor components treated with adaptive radiotherapy and concurrent chemotherapy., Case Presentation: Here we report the case of a 65-year-old male patient diagnosed with locally advanced thoracic esophageal squamous cell cancer, clinical T4bN1M0, stage IVA. Bronchoscopy and computed tomography (CT) revealed an almost complete obstruction of the lumen of the left bronchus due to compression by bulky primary esophageal tumor components. On admission, the patient presented with dyspnea and decreased arterial oxygen saturation. Chest radiography and CT on admission revealed mediastinal shift with left atelectasis, as opposed to findings from the chest radiography performed 26 days before admission. Because of the patient's overall good condition, we recommended definitive chemoradiotherapy instead of palliative bronchial stent placement. After obtaining the patient's consent, chemoradiotherapy was initiated on the following day and it comprised three-dimensional conformal radiotherapy with 60 Gy in 30 fractions with concurrent administration of cisplatin and 5-fluorouracil. During chemoradiotherapy, tumor location was monitored with cone-beam CT and chest radiography. Chemoradiotherapy on day 8 revealed no evidence of the mediastinal shift. CT simulation was reperformed to adjust the radiotherapy fields to account for geometrical changes induced by the absence of the mediastinal shift. Subsequently, the mediastinal shift and bronchial obstruction did not recur during the course of chemoradiotherapy. The patient completed the planned radiotherapy with concurrent and adjuvant chemotherapy, and no non-hematological grade ≥ 3 adverse events were observed. Complete response was confirmed 7 months after initiating chemoradiotherapy. Currently, no disease recurrence, dysphagia, or respiratory symptoms have been reported at 13 months after initiating chemoradiotherapy., Conclusions: In this study, a bulky primary esophageal tumor caused mediastinal shift due to ipsilateral bronchial obstruction. The close follow-up for monitoring resolution of the mediastinal shift during the course of chemoradiotherapy enabled adequate dose delivery to targets, thus reflecting the geometrical changes induced by the absence of the mediastinal shift. Adaptive radiotherapy technique was crucial for favorable patient outcomes in this challenging clinical situation.

A randomized phase III trial commenced in Japan in February 2018. Definitive chemoradiotherapy (CRT) with cisplatin plus 5-fluorouracil is the current standard treatment for locally advanced unresectable esophageal carcinoma. The purpose of this study is to confirm the superiority of induction chemotherapy with docetaxel plus cisplatin and 5-fluorouracil (DCF) followed by conversion surgery or definitive CRT over definitive CRT alone for overall survival (OS) in patients with locally advanced unresectable squamous-cell carcinoma of thoracic esophagus. A total of 230 patients will be accrued from 47 Japanese institutions over 4.5 years. The primary endpoint is OS, and the secondary endpoints are progression-free survival, complete response rate of CRT, response rate of DCF, adverse events of DCF and CRT, late adverse events and surgical complications. This trial has been registered at the Japan Registry of Clinical Trials as jRCTs031180181., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

During observations of mid-term and late-stage fetuses, we found a joint disk-like structure at the anterior component of the median atlanto-axial joint. At mid-term, the disk-like structure was thick (0.1-0.15 mm) relative to the sizes of bones surrounding the joint. However, it did not completely separate the joint cavity, and was absent in the inferior and/or central part of the cavity. This morphology was similar to the so-called fibroadipose meniscoid of the lumbar zygapophysial joint that is usually seen in adults. In mid-term fetuses, there was evidence suggesting that a mesenchymal tissue plate was separated from a roof of the joint cavity. In late-stage fetuses, the thickness (less than 0.15 mm) was usually the same as, or less than that at mid-term, and the disk-like structure was often flexed, folded and fragmented. Therefore, in contrast to the zygapophysial meniscoid as a result of aging, the present disk-like structure was most likely a temporary product during the cavitation process. It seemed to be degenerated in late-stage fetuses and possibly also in newborns. Anomalies at the craniocervical junction such as Chiari malformations might accompany this disk-like structure at the median atlanto-axial joint even in childhood., Competing Interests: Conflicts of Interest: No potential conflict of interest relevant to this article was reported., (Copyright © 2019. Anatomy & Cell Biology.)

Hypopharyngeal invasion would be a key finding in determining the extent of the irradiation fields in patients with cervical esophageal squamous cell carcinoma (CESCC). This study aimed to investigate the clinical outcomes of chemoradiotherapy using simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) omitting upper cervical lymph nodal irradiation in CESCC without hypopharyngeal invasion, and the dosimetric superiority of SIB-IMRT to 3D conformal radiotherapy (3DCRT). We retrospectively identified 21 CESCC patients without hypopharyngeal invasion [clinical Stage I/II/III/IV (M1LYM); 3/6/5/7] (UICC-TNM 7th edition) who underwent chemoradiotherapy using SIB-IMRT between 2009 and 2015. SIB-IMRT delivered 60 Gy to each primary tumor and the metastatic lymph nodes, and 48 Gy to elective lymph nodal regions, including Levels III and IV of the neck, supraclavicular, and upper mediastinal lymphatic regions, in 30 fractions. The overall survival rate, locoregional control rate, and initial recurrence site were evaluated. 3DCRT plans were created to perform dosimetric comparisons with SIB-IMRT. At a median follow-up of 64.5 months, the 5-year locoregional control and overall survival rates were 66.7% and 53.4%, respectively. Disease progressed in eight patients: all were locoregional progressions and no patients developed distant progression including upper cervical lymph nodal regions as initial recurrence sites. The planning study showed SIB-IMRT improved target coverage without compromising the dose to the organs at risk, compared with 3DCRT. In conclusion, omitting the elective nodal irradiation of the upper cervical lymph nodes was probably reasonable for CESCC patients without hypopharyngeal invasion. Locoregional progression remained the major progression site in this population., (© The Author(s) 2019. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.)

Background: The aim of this study was to assess the clinical outcomes of acoustic neuromas (ANs) treated with hypofractionated stereotactic radiotherapy (hypo-FSRT) prescribed at a uniform dose., Methods: Forty-seven patients with a unilateral AN were treated consecutively with hypo-FSRT between February 2007 and March 2012. Nineteen patients maintained a serviceable hearing status at the beginning of hypo-FSRT. The prescribed dose was 25 Gy delivered in five fractions per week to the isocenter, and the planning target volume was covered by the 80% isodose line., Results: The median follow-up and audiometric follow-up periods were 61 and 52 months, respectively. The estimated tumor control rate at 5 years was 90% (95% CI 76-96). The existence of the cystic component before hypo-FSRT had a significantly worse impact on tumor control (p = 0.02). The estimated hearing preservation rates at 1, 3 and 5 years were 68% (95% CI 42-84), 41% (95% CI 20-62) and 36% (95% CI 15-57), respectively. A borderline significant difference was identified in the mean biological effective dose with an α/β value of 3 Gy (BED 3 ) to the ipsilateral cochlea between the preserved hearing and hearing loss groups (19 Gy vs. 28 Gy) (p = 0.08)., Conclusions: Hypo-FSRT delivered in five fractions for unilateral ANs may achieve excellent tumor control with no severe facial or trigeminal complications. The mean BED 3 in the cochlea may impact the hearing preservation rate. Therefore, the cochlear dose should be as low as possible.

Background: To evaluate the role of androgen receptor-axis-targeted drugs (ARAT) in non-metastatic castration-resistant prostate cancer (nmCRPC) versus mCRPC., Methods: Chemotherapy-naive patients (n = 114) with CRPC who had no metastasis at the time of diagnosis were included in this retrospective study. All patients were treated with ARAT at Jikei University and its affiliated hospitals from July 2014 to March 2017. The patients were stratified into nmCRPC (n = 81) and mCRPC (n = 33) groups according to their metastatic status at ARAT induction. The primary outcome measure was difference in overall survival (OS) between groups from the time of CRPC diagnosis. The patients were compared for progression-free survival (PFS) and prostate-specific antigen (PSA) response. The predictors of OS were explored by a multivariate Cox model., Results: The baseline demographics did not differ significantly between the groups. The median observation period from the diagnosis of CRPC was 24.5 months (range: 3-135) and 20 months (range: 1-66) in nmCRPC and mCRPC groups, respectively. The nmCRPC group demonstrated better OS from the time of diagnosis of CRPC in Kaplan-Meier analysis than mCRPC group (86 months vs 40 months; P = 0.004), with similar results obtained for PFS (P = 0.048) and PSA response (P = 0.0014). Multivariate analysis demonstrated non-metastatic status, low PSA, and long PSA doubling time (PSADT) at ARAT induction as the significant predictors of longer OS (P = 0.044, 0.0001, and 0.026, respectively)., Conclusions: Early use of ARAT may improve OS, PFS, and PSA response in CRPC. Larger, prospective studies will be required to confirm our findings., (© 2018 Wiley Periodicals, Inc.)

Background: The purpose was to retrospectively evaluate the effect of intensity-modulated radiotherapy (IMRT) on gastrointestinal (GI) toxicities and outcomes compared to three-dimensional conformal radiotherapy (3DCRT) for locally advanced pancreatic cancer (LAPC)., Methods: We included 107 consecutive patients who underwent CRT for LAPC from September 2001 to March 2015; 80 patients underwent 3DCRT and 27 patients underwent IMRT. They were compared for GI toxicities, locoregional progression free survival (LRPFS), distant metastasis free survival (DMS), and overall survival (OS)., Results: Median radiation dose and fractions for 3DCRT and IMRT were 54 Gy/30 fr. and 48 Gy/15 fr. The regimens of CRT consisted of weekly gemcitabine 250 mg/m 2 (for 3DCRT) or 1000 mg/m 2 (for IMRT). Acute GI toxicity ≥grade 2 occurred in 32 patients (40%) treated with 3DCRT compared with five patients (19%) treated with IMRT. Late GI toxicity of grade 3 occurred in 10 patients (12%) treated with 3DCRT and one patient (4%) treated with IMRT. Patients who underwent IMRT had superior 1-year LRPFS (73.1% vs. 63.2%, p = 0.035) and 1-year OS (92.3% vs. 68.2%, p = 0.037) as compared with those treated with 3DCRT. Multivariate analysis showed that in IMRT patients, higher dose (≥45 Gy) was an independent factor for better LRPFS and OS., Conclusions: LAPC patients treated with hypofractionated full-dose gemcitabine IMRT had improved OS and LRPFS without increased GI toxicities when compared to those of patients treated with conventionally fractionated low dose gemcitabine 3DCRT. In IMRT patients, higher dose was an independent favorable prognostic factor for better LRPFS and OS, which suggests that dose escalation with IMRT for LAPC is a promising strategy.

This study sought to evaluate the effect of fasting time prior to 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) on myocardial accumulation of FDG in patients receiving radiotherapy for esophageal carcinoma, and the spatial relationship between the irradiated dose and myocardial accumulation of FDG. Forty-one patients with thoracic esophageal carcinoma received FDG-PET with <18-h (24 patients) or ≥18-h (17 patients) fasting status. Their myocardial accumulation patterns of FDG were categorized using the maximal standardized uptake value (SUVmax) into three types: physiological, focal and no pathological accumulation. The incidence rates of each pattern were then compared using the Fisher's exact test between two types of fasting, ≥18-h and <18-h, prior to FDG-PET. Additionally, the left ventricle was defined using four subsites depending on the irradiated doses, and the SUVmax values were compared among the subsites using the Kruskal-Wallis test. The incidence of the physiological accumulation pattern decreased significantly more in the ≥18-h fasting status group than in the <18-h fasting group (18% versus 71%, P = 0.002), and the focal accumulation of FDG was detected at a significantly higher rate (65% versus 13%, P = 0.001). The left ventricular subsites receiving the higher doses showed significantly higher SUVmax values than did the subsites receiving the lower doses (P < 0.001). In conclusion, radiotherapy was associated with abnormal myocardial accumulation of FDG. Long fasting for 18 h or more prior to FDG-PET would be useful in detecting subsequent myocardial damage from chemoradiotherapy compared with <18-h fasting prior to FDG-PET.

Background: The aim of this study was to identify the long-term clinical outcome of definitive radiotherapy using three-dimensional conformal radiotherapy (3DCRT) for cervical esophageal squamous cell carcinoma (CESCC)., Methods: We retrospectively reviewed the medical records of 30 patients with CESCC [clinical stage I/II/III/IV(M1LYM); 3/2/12/13] (TNM 7th edition) who underwent definitive radiotherapy using 3DCRT between 2000 and 2014 in our institution. The median prescribed dose for the gross tumor and metastatic lymph nodes was 60 Gy. Twenty-six patients underwent elective nodal irradiation for the neck node levels III, IV, and VI and for upper mediastinal lymph nodes with a median dose of 40 Gy. Twenty-six patients underwent concurrent chemotherapy. Initial disease progression sites, locoregional control (LRC) rate, overall survival (OS) rate, and toxicities were retrospectively evaluated. A univariate analysis was performed to identify prognostic factors., Results: With a median follow-up of 110 months, the 5- and 10-year LRC rates were 43.7% and 37.4%, respectively. The 5- and 10-year OS rates were 48.3% and 40.2%, respectively. Locoregional, distant and both area accounted for 83%, 6% and 11% of the initial progression sites. Unresectable status and M1LYM were significantly associated with poor LRC (p < 0.05) and OS (p < 0.05). Grade 3 acute non-hematological toxicity occurred in 13.3% of patients. During the follow-up, patients without any disease progression did not need a permanent gastrostomy tube or tracheostomy. Late toxicity events, including hypothyroidism and cardiovascular disease, were observed; 5- and 10-year cumulative incidence rates of grade 2 hypothyroidism and ≥grade 3 cardiovascular disease were 31.6% and 62.5%, and 17.5% and 21.3%, respectively., Conclusions: Definitive radiotherapy yields a cure for patients with CESCC while preserving their laryngopharyngeal function. The poor LRC rate in the advanced stage needs to be overcome for a better prognosis. As the incidence of radiation-induced hypothyroidism and cardiovascular disease was not low, long-term survivors should be followed up for these symptoms.

(Purpose) To describe our initial experience in salvage cryoablation targeting recurrent lesions after definitive irradiation for prostate cancer. (Methods) Eligible patients for this treatment were those who developed biochemical failure after definitive radiotherapy for localized prostate cancer, but without distant metastasis, and with solid lesions identifiable on multiparametric magnetic resonance imaging (mpMRI). Histological proof of recurrence with mapping biopsy covering corresponding sites was obtained. Two to four cryoprobes were inserted transperineally into the prostate under general anesthesia with extensive lithotomy position. The rapid expansion of argon gas cryogen through a small opening within the cryoprobe cools itself to make an ice ball and the quick exchange to helium gas induces an active thawing phase. Entire procedure is monitored and guided with the use of transrectal ultrasonography. Postoperative follow-up included patient interview, digital rectal examination, prostate specific antigen (PSA) testing and quality of life (QOL) monitoring using IPSS and IIEF-5 at 1, 3, 6 and 12 months postoperatively. Changes of mpMRI findings with time, particularly at one month, were used to judge immediate treatment impact. (Results) Five patients underwent salvage cryoablation between October 2015 and September 2016. No grade 3/4 complications such as rectal fistula or urethral stenosis were experienced. Mean and maximal percent decline of PSA from baseline levels at 1, 3, 6 and 12 months following cryoablation were 72.2 and 94.7%, 79.4% and 93.9%, 78.2% and 92.1%, 79.6% and 90.9%, respectively. Posttreatment IPSS showed temporary worsening with average changes in score of 1.8, 1.5, 1.6, and 1.0 times over baseline levels, respectively. IPSS score returned to the baseline in one at six months and two at 12 months. Two of 5 patients were sexually active prior to therapy and thus evaluable. Both showed significant decline in IIEF score by 95% at 12 months. No patients showed any signs of recurrence. mpMRI at one month following cryoablation confirmed complete disappearance of visible lesions in all cases. (Conclusions) Salvage cryoablation for recurrent lesions of prostate cancer after definitive radiotherapy is feasible with minimal morbidity. Both oncological outcome and adverse events should be monitored carefully with longer follow up.