Search

Backgrounds: We aimed to clarify the outcomes of postoperative radiotherapy (PORT) after salvage neck dissection for cervical lymph node (LN) recurrence in oral cavity cancer. Methods: We retrospectively evaluated overall survival (OS), recurrence‐free survival (RFS), recurrence patterns, and adverse events of 51 patients with high‐risk features receiving PORT after salvage neck dissection between 2009 and 2019. Results: After a median follow‐up of 7.4 years from PORT initiation, the 7‐year OS and RFS rates were 66.3% (95% CI: 54.0–81.3) and 54.6% (95% CI: 42.1–70.9), respectively. Age <70 years and isolated LN recurrence were significantly associated with longer OS and RFS. Among the 22 patients who experienced recurrence, 14 experienced recurrence within the radiation field. PORT‐related grade 3 acute mucositis (35%) and late adverse events (osteoradionecrosis [4%] and laryngeal stenosis [2%]) were observed. Conclusions: PORT after salvage neck dissection for cervical LN recurrence achieved good survival with acceptable toxicity. [ABSTRACT FROM AUTHOR]

Background: We evaluated clinical and dosimetric outcomes of radiotherapy using two anterior oblique portals (AOP), to reduce the dose to the bilateral internal carotid arteries (CAs) and pharyngeal constrictor muscle (PCM) during early‐stage glottic cancer (ESGC) treatment. Methods: We identified patients with ESGC who underwent definitive radiotherapy between June 2014 and May 2020. Results: Among the 66 patients, 32 (48%) underwent radiotherapy using AOP, and the remaining underwent typical radiotherapy using parallel opposed lateral portals (POLP). The median follow‐up duration was 53 months. No significant differences were observed in the 5‐year local failure (0%/9.4%), progression‐free survival (90.6%/90.8%), and overall survival (90.6%/91.0%) rates between the two groups. The grade ≥2 acute mucositis incidence rate was significantly lower in the AOP group (44%/85%). Radiotherapy using AOP maintained an adequate dose coverage to the target while markedly reducing the CAs and PCM doses. Conclusion: Radiotherapy with AOP resulted in favorable clinical and dosimetric outcomes. [ABSTRACT FROM AUTHOR]

Background: This study aimed to compare the outcomes of proton beam therapy (PBT) and carbon ion radiotherapy (CIRT) by a systematic review and meta‐analysis of the existing clinical evidence. Methods: A systematic literature search was performed to identify studies comparing the clinical outcomes of PBT and CIRT. The included studies were required to report oncological outcomes (local control [LC], progression‐free survival [PFS], or overall survival [OS]) or adverse events. Results: Eighteen articles comprising 1857 patients (947 treated with PBT and 910 treated with CIRT) were included in the analysis. The pooled analysis conducted for the overall population yielded average hazard ratios of 0.690 (95% confidence interval (CI), 0.493–0.967, p = 0.031) for LC, 0.952 (95% CI, 0.604–1.500, p = 0.590) for PFS, and 1.183 (0.872–1.607, p = 0.281) for OS with reference to CIRT. The subgroup analyses included patients treated in the head and neck, areas other than the head and neck, and patients with chordomas and chondrosarcomas. These analyses revealed no significant differences in most outcomes, except for LC in the subgroup of patients treated in areas other than the head and neck. Adverse event rates were comparable in both groups, with an odds ratio (OR) of 1.097 (95% CI, 0.744–1.616, p = 0.641). Meta‐regression analysis for possible heterogeneity did not demonstrate a significant association between treatment outcomes and the ratio of biologically effective doses between modalities. Conclusion: This study highlighted the comparability of PBT and CIRT in terms of oncological outcomes and adverse events. [ABSTRACT FROM AUTHOR]

Background: The entire pharynx should be observed endoscopically to avoid missing pharyngeal lesions. An artificial intelligence (AI) model recognizing anatomical locations can help identify blind spots. We developed and evaluated an AI model classifying pharyngeal and laryngeal endoscopic locations. Methods: The AI model was trained using 5382 endoscopic images, categorized into 15 anatomical locations, and evaluated using an independent dataset of 1110 images. The main outcomes were model accuracy, precision, recall, and F1‐score. Moreover, we investigated focused regions in the input images contributing to the model predictions using gradient‐weighted class activation mapping (Grad‐CAM) and Guided Grad‐CAM. Results: Our AI model correctly classified pharyngeal and laryngeal images into 15 anatomical locations, with an accuracy of 93.3%. The weighted averages of precision, recall, and F1‐score were 0.934, 0.933, and 0.933, respectively. Conclusion: Our AI model has an excellent performance determining pharyngeal and laryngeal anatomical locations, helping endoscopists notify of blind spots. [ABSTRACT FROM AUTHOR]

Radiotherapy (RT) combined with immune checkpoint inhibitors has recently produced outstanding results and is expected to be adaptable for various cancers. However, the precise molecular mechanism by which immune reactions are induced by fractionated RT is still controversial. We aimed to investigate the mechanism of the immune response regarding multifractionated, long‐term radiation, which is most often combined with immunotherapy. Two human esophageal cancer cell lines, KYSE‐450 and OE‐21, were irradiated by fractionated irradiation (FIR) daily at a dose of 3 Gy in 5 d/wk for 2 weeks. Western blot analysis and RNA sequencing identified type I interferon (IFN) and the stimulator of IFN genes (STING) pathway as candidates that regulate immune response by FIR. We inhibited STING, IFNAR1, STAT1, and IFN regulatory factor 1 (IRF1) and investigated the effects on the immune response in cancer cells and the invasion of surrounding immune cells. We herein revealed type I IFN‐dependent immune reactions and the positive feedback of STING, IRF1, and phosphorylated STAT1 induced by FIR. Knocking out STING, IFNAR1, STAT1, and IRF1 resulted in a poorer immunological response than that in WT cells. The STING‐KO KYSE‐450 cell line showed significantly less invasion of PBMCs than the WT cell line under FIR. In the analysis of STING‐KO cells and migrated PBMCs, we confirmed the occurrence of STING‐dependent immune activation under FIR. In conclusion, we identified that the STING‐IFNAR1‐STAT1‐IRF1 axis regulates immune reactions in cancer cells triggered by FIR and that the STING pathway also contributes to immune cell invasion of cancer cells. [ABSTRACT FROM AUTHOR]

Determination of the primary tumor in periampullary region carcinomas can be difficult, and the pathological assessment and clinicopathological characteristics remain elusive. In this study, we investigated the current recognition and practices for periampullary region adenocarcinoma with an indeterminable origin among expert pathologists through a cognitive survey. Simultaneously, we analyzed a prospective collection of cases with an indeterminable primary tumor diagnosed from 2008 to 2018 to elucidate their clinicopathological features. All cases with pathological indeterminable primary tumors were reported and discussed in a clinicopathological conference to elucidate if it was possible to distinguish the primary tumor clinically and pathologically. From the cognitive survey, over 85% of the pathologists had experienced cases with indeterminable primary tumors; however, 70% of the cases was reported as pancreatic cancer without definitive grounds. Interpretation of the main tumor mass varied, and no standardized method was developed to determine the primary tumor. During a prospective study, 42 of the 392 periampullary carcinoma cases (10.7%) were considered as tumors with a pathological indeterminable origin. After the clinicopathological conferences, 21 (5.4%) remained indeterminable and were considered final indeterminable cases. Histological studies showed that the tumors spread along both the bile duct and main pancreatic duct; this was the most representative finding of the final indeterminable cases. This study is the first to elucidate and recognize the current clinicopathological features of periampullary region adenocarcinomas with an indeterminable origin. Adequate assessment of primary tumors in periampullary region carcinomas will help to optimize epidemiological data of pancreatic and bile duct cancer. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to evaluate accelerated fractionated radiotherapy (AFRT) without elective nodal irradiation (ENI) for T3N0 glottic cancer (GC) without vocal cord fixation, especially in comparison with chemoradiotherapy (CRT) and hyperfractionated radiotherapy (HFRT) both of which included ENI. Methods: The medical charts of patients with T3N0GC without cord fixation received definitive radiotherapy between June 2005 and March 2018 were reviewed. Results: A total of 74 patients were analyzed. After a median follow‐up time of 46 months (range, 12‐141), 3‐year local failure in AFRT/CRT/HFRT (n = 41/10/23) was 10%/20%/26%, 3‐year regional failure 6%/0%/9%, 3‐year progression‐free survival 71%/69%/74%, and 3‐year overall survival 77%/100%/87%. There were no significant differences among three groups in recurrence or survival. Grade 3 adverse events (AEs) were noted in 5/2/8 patients (12%/20%/35%) in AFRT/CRT/HFRT, respectively. There were no Grade 4/5 AEs. Conclusions: AFRT without ENI is an effective and feasible treatment for T3N0GC without cord fixation. [ABSTRACT FROM AUTHOR]

Background and Aim: Surgical resection is the standard local therapy for patients with colorectal liver metastases (CRLM). However, elderly and vulnerable patients sometimes have various organ dysfunctions. We have to conduct nonsurgical local therapies for those patients who might not tolerate surgery or systemic chemotherapy. Methods: We retrospectively reviewed medical records of 254 patients who underwent local therapies, including surgery, radiofrequency ablation (RFA), and stereotactic body radiation therapy (SBRT), for CRLM from January 2010 to December 2016, at seven tertiary‐care institutions in Japan. This study was designed to include elderly, vulnerable patients who received local therapy for CRLM. For those undergoing liver resection, only those having one or more points of the Charlson comorbidity index (CCI) were enrolled. Results: Of the total 169 enrolled patients, 122 patients underwent surgery, 42 RFA, and 5 SBRT as the first local therapy for CRLM. Median overall survival from the first local therapy was 5.9 years for the surgery group, 2.7 years for the RFA group, and 3.8 years for the SBRT group. The proportion of the patients with CCI ≧3 was significantly higher in the group of RFA/SBRT than surgery (P < 0.0001). In selected patients with CCI ≧3, there was no difference of the median survival time between the surgery group and the RFA group. Conclusions: We could have other treatment options to provide nonsurgical local therapies (RFA/SBRT) for elderly, vulnerable CRLM patients who have risks for surgery. [ABSTRACT FROM AUTHOR]

Background: In the case of liver metastasis (LM), tumors showing the replacement growth pattern (RGP), in which metastatic cells infiltrate and replace hepatocytes with minimal desmoplastic reaction and inflammatory cell infiltration, associate with a poor prognosis. The heterogeneity, frequency, and prognostic value of the RGP in LM from pancreatic cancer (PCa) are not well known. Methods: In the circumference of treatment‐naïve resected LMs from patients with PCa, the heterogeneity of the GP was assessed. Next, the clinicopathological features of LMs showing the RGP in needle biopsy specimens were investigated in patients with treatment‐naïve advanced PCa. Results: Thirteen of the 14 (93%) in all resected LMs and 7 of the 9 (78%) in RGP component GP in resected LMs showed homogeneous GP. A RGP was found in 50% of the needle biopsy specimens of LMs obtained from 107 patients. The median overall survival times in the RGP group and non‐RGP group were 3.6 and 10.4 months. Multivariate analysis identified RGP as an independent poor prognostic factor. Median value of CD8 positive percentage in RGP was lower than that in non‐RGP (0.75 vs 1.46, P =.04). Median overall survival times in low CD8 groups tend to be shorter than those in high CD8 group (8.2 vs 4.2 months). Conclusion: Most LMs from PCa show a homogeneous GP. The RGP was observed in about a half of the LMs from PCa patients, and was identified as a poor prognostic factor. [ABSTRACT FROM AUTHOR]

Background: Extranodal metastasis is an isolated tumor nodule without a residual lymph node structure and has been reported as a poor prognostic factor in gastric cancer. The aim of this study is to assess the prognostic value of extranodal metastasis, especially from the viewpoint of its anatomical distribution. Methods: A total of 139 consecutive gastric cancer patients who underwent curative surgery with lymph node metastasis between 2008 and 2009 were included. Clinicopathological features and patient survival outcomes were retrospectively assessed. Patients with extranodal metastasis were subdivided into two groups: perigastric extranodal metastasis, located near the perigastric area (#1–#7 according to the Japanese classification of gastric carcinoma 15th edition), and extra-perigastric extranodal metastasis, located alongside the major vessels (#8–#12). Results: Extranodal metastasis was found in 51 patients (37%), and it was more frequent in those with bulky, ≥pT3, and pStage III tumors. All patients with extra-perigastric extranodal metastasis had recurrence, resulting in a 0% 5-year overall survival rate, which was significantly worse than that of patients with perigastric extranodal metastasis (59%), or those without extranodal metastasis (84%; P < 0.001). Multivariable analysis identified the presence of extra-perigastric extranodal metastasis as an independent poor prognostic factor. Conclusions: Extranodal metastasis, especially extra-perigastric extranodal metastasis, was a pivotal poor prognostic factor in node-positive gastric cancer. Recognizing extra-perigastric extranodal metastasis would help provide optimal therapeutic options to these high-risk patients. [ABSTRACT FROM AUTHOR]

Introduction: To clarify the efficacy and safety of hypofractionated proton beam therapy (PBT) for centrally located lung cancer.Methods: We retrospectively reviewed 39 patients who received hypofractionated [≧3 Gy (relative biological effectiveness: RBE)/fraction] PBT for centrally located cT1-2N0M0 (8th edition) lung cancer between 1999 and 2015. A tumour within 2 cm of the proximal bronchial tree was defined as a centrally located tumour.Results: Twenty-four patients (62%) were treated with 80 Gy (RBE) in 20 fractions (112 Gy10 ), whereas eight (21%) were treated with 66 Gy (RBE) in 10 fractions (109.56 Gy10 ). The median follow-up period for censored patients was 48 months (range: 4-140). The 2-year progression-free survival (PFS) and overall survival (OS) rates were 86 and 100% for T1 disease and 56 and 94% for T2 disease, respectively. Patients who received 110 Gy10 or higher showed significantly better PFS than those who received less than 110 Gy10 , while no significant difference was noted in OS between the two groups. The sites of the first progression were local in six patients (27%), regional in seven (32%), distant in seven (32%), and local and distant in two (9%). Among the 13 patients with loco-regional recurrence, only two (15%) received treatments with curative intent. Dyspnoea of grade 3 was noted in one patient (3%), and pneumonitis of grade 2 was noted in four patients (10%).Conclusion: Hypofractionated PBT may be a very safe and effective treatment option for centrally located early lung cancer. [ABSTRACT FROM AUTHOR]

To evaluate the accuracy of commercially available hybrid deformable image registration (DIR) algorithms when using planning CT (pCT) and daily cone‐beam computed tomography (CBCT) in radiation therapy for prostate cancer. The hybrid DIR algorithms in RayStation and MIM Maestro were evaluated. Contours of the prostate, bladder, rectum, and seminal vesicles (SVs) were used as region‐of‐interest (ROIs) to guide image deformation in the hybrid DIR and to compare the DIR accuracy. To evaluate robustness of the hybrid DIR for prostate cancer patients with organs with volume that vary on a daily basis, such as the bladder and rectum, the DIR algorithms were performed on ten pairs of CT volumes from ten patients who underwent prostate intensity‐modulated radiation therapy or volumetric modulated arc therapy. In a visual evaluation, MIM caused unrealistic image deformation in soft tissues, organs, and pelvic bones. The mean dice similarity coefficient (DSC) ranged from 0.46 to 0.90 for the prostate, bladder, rectum, and SVs; the SVs had the lowest DSC. Target registration error (TRE) at the centroid of the ROIs was about 2 mm for the prostate and bladder, and about 6 mm for the rectum and SVs. RayStation did not cause unrealistic image deformation, and could maintain the shape of pelvic bones in most cases. The mean DSC and TRE at the centroid of the ROIs were about 0.9 and within 5 mm generally. In both software programs, the use of ROIs to guide image deformation had the possibility to reduce any unrealistic image deformation and might be effective to keep the DIR physically reasonable. The pCT/CBCT DIR for the prostate cancer did not reduce the DIR accuracy because of the use of ROIs to guide the image deformation. [ABSTRACT FROM AUTHOR]

Abstract: To evaluate preliminary results of proton radiotherapy (PRT) for pediatric patients with rhabdomyosarcoma (RMS). From 1987 to 2014, PRT was conducted as initial radiotherapy in 55 patients (35 males, 20 females, median age 5 years, range 0–19) with RMS at four institutes in Japan. Thirty‐one, 18, and six patients had embryonal, alveolar, and other RMS, respectively. One, 11, 37, and six patients were in IRSG groups I, II, III, and IV, respectively, and the COG risk group was low, intermediate, and high for nine, 39, and seven patients, respectively. The irradiation dose was 36–60 GyE (median: 50.4 GyE). The median follow‐up period was 24.5 months (range: 1.5–320.3). The 1‐ and 2‐year overall survival rates were 91.9% (95% CI: 84.3–99.5%) and 84.8% (95% CI 75.2–94.3%), respectively, and these rates were 100% and 100%, 97.1% and 90.1%, and 57.1% and 42.9% for COG low‐, intermediate‐, and high‐risk groups, respectively. There were 153 adverse events of Grade ≥3, including 141 hematologic toxicities in 48 patients (87%) and 12 radiation‐induced toxicities in nine patients (16%). Proton‐specific toxicity was not observed. PRT has the same treatment effect as photon radiotherapy with tolerable acute radiation‐induced toxicity. [ABSTRACT FROM AUTHOR]

Abstract: This is the first multi‐institutional retrospective survey of the long‐term outcomes of proton therapy (PT) for prostate cancer in Japan. This retrospective analysis comprised prostate cancer patients treated with PT at seven centers between January 2008 and December 2011 and was approved by each Institutional Review Board. The NCCN classification was used. Biochemical relapse was based on the Phoenix definition (nadir + 2.0 ng/mL). Toxicities were evaluated with the Common Terminology Criteria for Adverse Events version 4.0. There were 215, 520, and 556 patients in the low‐risk, intermediate‐risk, and high‐risk groups, respectively. The median follow‐up period of surviving patients was 69 months (range: 7–107). Among all patients, 98.8% were treated using a conventional fractionation schedule and 1.2% with a hypofractionation schedule; 58.5% and 21.5% received neoadjuvant and adjuvant androgen deprivation therapy, respectively. The 5‐year biochemical relapse‐free survival (bRFS) and overall survival rates in the low‐risk, intermediate‐risk, and high‐risk groups were 97.0%, 91.1%, and 83.1%, and 98.4%, 96.8%, and 95.2%, respectively. In the multivariate analysis, the NCCN classification was a significant prognostic factor for bRFS, but not overall survival. The incidence rates of grade 2 or more severe late gastrointestinal and genitourinary toxicities were 4.1% and 4.0%, retrospectively. This retrospective analysis of a multi‐institutional survey suggested that PT is effective and well‐tolerated for prostate cancer. Based on this result, a multi‐institutional prospective clinical trial (UMIN000025453) on PT for prostate cancer has just been initiated in order to define its role in Japan. [ABSTRACT FROM AUTHOR]

Purpose Hypo-fractionated proton beam therapy (PBT) is an approach that has been increasingly explored over the past decade. It requires high geometric accuracy for targeting of the PBT beams. However, image-guided PBT is currently commonly performed with kV X-ray images of bony anatomy. A dynamic adaptive passive scattering PBT system using computed tomography-based three-dimensional image guidance was developed, and its effectiveness was then evaluated retrospectively in patients with nonsmall cell lung cancer (NSCLC). Methods The dynamic adaptive PBT system consisted of computed tomography-based image registration and proton dose calculation using a simplified Monte Carlo algorithm, with a range adaptation system that could adjust the range shifter thickness to alter the dose distribution. Three patients were retrospectively analyzed. All plans, which each had a total dose of 60 Gy (relative biological effectiveness; RBE), were generated using two fields (Gantry angles: 270 degree and 180 degree) in a passive scattering method. Three dose distributions were generated for each patient according to the following different registrations: bone registration, tumor registration, and tumor registration with range adaptation. The following dosimetric parameters were compared with the original plan: target dose coverage at D95% for the clinical target volume (CTV), homogeneity of D5% to D95% for the CTV, and dose distributions in normal tissue (Dmax of Spinal cord and V20 Gy of lung). Results For the bone registration method, the average D95% and D5% to D95% for the CTV showed average differences from the original plan of −3.7 ± 4.1 Gy (mean ± 1SD; RBE) and 3.6 ± 3.9 Gy (RBE) respectively. The tumor registration method achieved better coverage than the bone registration method, although the dosimetric parameters for coverage and homogeneity still showed average differences in −2.0 ± 2.3 Gy (RBE) and 1.9 ± 2.2 Gy (RBE) respectively. The range adaptive plan showed comparable coverage and homogeneity [D95%: −1.0 ± 1.3 Gy (RBE) and D5% to D95%: 0.9 ± 1.0 Gy (RBE) on average] to the original plan, as well as demonstrating similar normal tissue sparing. The approach could be completed in less than 10 min, including CT acquisition, image registration, dose recalculation with range optimization, and the operator's visual verification. Conclusions The tumor dose coverage in patients with NSCLC may deteriorate as a result of respiratory or body movement if daily proton range adaptation is not performed. Our approach may provide higher geometric accuracy for localization of the tumor, and the dynamic range adaptation enables us to achieve the planned dose distribution for hypo-fractionated PBT in the lung. [ABSTRACT FROM AUTHOR]

We conducted a retrospective, nationwide multicenter study to evaluate the clinical outcomes of proton beam therapy for bone sarcomas of the skull base and spine in Japan. Eligibility criteria included: (i) histologically proven bone sarcomas of the skull base or spine; (ii) no metastases; (iii) ≥20 years of age; and (iv) no prior treatment with radiotherapy. Of the 103 patients treated between January 2004 and January 2012, we retrospectively analyzed data from 96 patients who were followed-up for >6 months or had died within 6 months. Seventy-two patients (75.0%) had chordoma, 20 patients (20.8%) had chondrosarcoma, and four patients (7.2%) had osteosarcoma. The most frequent tumor locations included the skull base in 68 patients (70.8%) and the sacral spine in 13 patients (13.5%). Patients received a median total dose of 70.0 Gy (relative biological effectiveness). The median follow-up was 52.6 (range, 6.3-131.9) months. The 5-year overall survival, progression-free survival, and local control rates were 75.3%, 49.6%, and 71.1%, respectively. Performance status was a significant factor for overall survival and progression-free survival, whilst sex was a significant factor for local control. Acute Grade 3 and late toxicities of ≥Grade 3 were observed in nine patients (9.4%) each (late Grade 4 toxicities [ n = 3 patients; 3.1%]). No treatment-related deaths occurred. Proton beam therapy is safe and effective for the treatment of bone sarcomas of the skull base and spine in Japan. However, larger prospective studies with a longer follow-up are warranted. [ABSTRACT FROM AUTHOR]

Proton beam therapy ( PBT) is a potential new alternative to treatment with photon radiotherapy that may reduce the risk of late toxicity and secondary cancer, especially for pediatric tumors. The goal of this study was to evaluate the long-term benefits of PBT in cancer survivors. A retrospective observational study of pediatric patients who received PBT was performed at four institutions in Japan. Of 343 patients, 62 were followed up for 5 or more years. These patients included 40 males and 22 females, and had a median age of 10 years (range: 0-19 years) at the time of treatment. The irradiation dose ranged from 10.8 to 81.2 GyE (median: 50.4 GyE). The median follow-up period was 8.1 years (5.0-31.2 years). The 5-, 10- and 20-year rates for grade 2 or higher late toxicities were 18%, 35% and 45%, respectively, and those for grade 3 or higher late toxicities were 6%, 17% and 17% respectively. Univariate analysis showed that the irradiated site (head and neck, brain) was significantly associated with late toxicities. No malignant secondary tumors occurred within the irradiated field. The 10- and 20-year cumulative rates for all secondary tumors, malignant secondary tumors, and malignant nonhematologic secondary tumors were 8% and 16%, 5% and 13%, and 3% and 11%, respectively. Our data indicate that PBT has the potential to reduce the risk of late mortality and secondary malignancy. Longer follow-up is needed to confirm the benefits of PBT for pediatric tumors. [ABSTRACT FROM AUTHOR]

Recent progress in the treatment for pediatric malignancies using a combination of surgery, chemotherapy, and radiotherapy has improved survival. However, late toxicities of radiotherapy are a concern in long-term survivors. A recent study suggested reduced secondary cancer and other late toxicities after proton beam therapy ( PBT) due to dosimetric advantages. In this study, we evaluated the safety and efficacy of PBT for pediatric patients treated in Japan. A retrospective observational study in pediatric patients who received PBT was performed. All patients aged <20 years old who underwent PBT from January 1983 to August 2014 at four sites in Japan were enrolled in the study. There were 343 patients in the study. The median follow-up periods were 22.6 months (0.4-374.3 months) for all patients and 30.6 months (0.6-374.3 months) for survivors. The estimated 1-, 3-, 5-, and 10-year survival rates were 82.7% (95% CI: 78.5-87.0%), 67.4% (61.7-73.2%), 61.4% (54.8-67.9%), and 58.7% (51.5-65.9%), respectively. Fifty-two events of toxicity ≥ grade 2 occurred in 43 patients. Grade 4 toxicities of myelitis, visual loss (two cases), cerebral vascular disease, and tissue necrosis occurred in five patients. This study provides preliminary results for PBT in pediatric patients in Japan. More experience and follow-up with this technique are required to establish the efficacy of PBT in this patient population. [ABSTRACT FROM AUTHOR]

Pathological studies on the different histological effects between neoadjuvant chemotherapy (NAC) and preoperative chemoradiation therapy (preoperative CRT) have not been performed. The purpose of this study is to elucidate the histological differences in tissue received from NAC and preoperative CRT for rectal cancer to evaluate whether a pathological assessment method used after CRT can be applied for NAC. One hundred and thirty-eight patients were enrolled in this study; 88 patients underwent their operations after preoperative CRT or NAC, and 50 patients underwent surgery only. Residual tumor area was measured using morphometry software and we compared the stromal component of myofibroblasts, immune cells, and vasculature to elucidate the difference of therapeutic effect between them. The grade of reduction after preoperative CRT was more prominent than that seen in NAC. Also, ypT downstaging was more prominent in preoperative CRT than in NAC, and ypN downstaging was more frequent in NAC than in preoperative CRT. Preoperative CRT showed more marked myofibroblasts and fewer immune cells than did NAC, which indicates different effects on the cancer microenvironment. Our histological results suggest different effects between NAC and preoperative CRT on tumor tissue. The best assessment method available for a variable therapeutic protocol should be further investigated. [ABSTRACT FROM AUTHOR]

Although new classifications for neuroendocrine tumors were established by the World Health Organization, the current procedures and terms used in pathology laboratories are not known. A Web-based questionnaire was distributed to 491 institutions affiliated with the Japanese Society for Cancer of the Colon and Rectum, and 150 participated. The questionnaires included questions regarding routine pathological reporting, staining, and assessment of neuroendocrine tumors. Next, the time taken to assess Ki-67 index and mitotic count according to recommendation was evaluated to determine its feasibility. Most laboratories recorded diagnostic term, depth of invasion, size, lymph-vascular invasion, Ki-67 index, and mitotic count. However, only 32.2% reported tumor stage. Chromogranin A and synaptophysin were common neuroendocrine markers. D2-40 and elastica stain were frequently used to confirm lymph-vascular invasion. Only 62.1% counted more than 500 cells for the Ki-67 index, and only 17.0% counted more than 50 fields for the mitotic count, as suggested by the recommendations. Median time of 7 cases was 18.0 and 27.3 min to assess mitotic count in 50 fields with Ki-67 index in 500 and 2000 cells, respectively. For more standardized pathological reporting, education about standardized staging systems are needed in Japan. Practical and standardized procedures for mitotic index and Ki-67 index are also required. [ABSTRACT FROM AUTHOR]

We conducted a phase II study to evaluate the efficacy and safety of chemoradiotherapy concurrent with S-1 plus cisplatin in patients with unresectable locally advanced squamous cell carcinoma of the head and neck. Chemotherapy consisted of S-1 twice daily on days 1-14 at 60 mg/m2/day and cisplatin at 20 mg/m2/day on days 8-11, repeated twice at a 5-week interval. Single daily radiation of 70 Gy in 35 fractions was given concurrently starting on day 1. For patients achieving an objective response after chemoradiotherapy, two additional cycles of chemotherapy were administered. Of the 45 enrolled patients, the percentage of clinical complete remission, the primary endpoint, was 64.4% (8 complete response, 21 good partial response) on central review. After a median follow-up of 3.52 years, 3-year local progression-free survival was 62.2%, with 3-year progression-free survival of 60.0%, 3-year overall survival of 64.4%, and 3-year time to treatment failure of 48.9%. Grade 3 or 4 toxicity included pharyngeal mucositis (46.7%), oral mucositis (44.4%), dysphagia (46.7%), anorexia (42.2%), radiation dermatitis (26.7%), neutropenia (26.7%), and febrile neutropenia (4.4%). No treatment-related deaths were observed. This combination showed promising efficacy with acceptable toxicities. [ABSTRACT FROM AUTHOR]

Background Accelerated fractionation radiotherapy (RT) was administered in an attempt to improve the local control rates in patients with T1/T2 N0 glottic cancer. Methods Medical charts of 148 consecutive patients who had undergone RT using 2.4 Gray (Gy) once-daily fractionation between July 1999 and April 2007 were reviewed. Results Of 104 patients with T1 disease treated by RT, 82 received 60 Gy/25 fractions, and the remaining 22 with large tumor volumes and/or slow response to RT received 64.8 Gy/27 fractions. All 44 patients with T2 disease received 64.8 Gy/27 fractions. The 5-year local control and overall survival (OS) rates were 93% and 96%, respectively, in patients with T1 disease, and 77% and 91%, respectively, in patients with T2 disease. No severe acute toxicities were observed, although 2 patients (1%) developed severe late toxicity. Conclusion Accelerated RT for early glottic cancer is feasible, with encouraging local control rates. © 2014 Wiley Periodicals, Inc. Head Neck 37: 579-584, 2015 [ABSTRACT FROM AUTHOR]

Objective: To determine the efficacy of stereotactic radiotherapy (SRT) in the treatment of recurrent nasopharyngeal carcinoma. Study Design: A retrospective review of the outcome of SRT for patients with recurrent nasopharyngeal carcinomas following definitive conventional radiation therapy. Methods: Five patients were treated with daily static multiportal irradiation. Two Gy was administered with eight isocentric portals in a single plane 5 days a week, and the plane was changed for every 20 to 30 Gy. Of these patients, three had poorly differentiated squamous cell carcinoma. Tumor sizes ranged from 1 to 15 cm3, with a median size 3.2 cm3. Median follow-up time from SRT was 34 months (range, 4-61 mo). Results: Four of five recurrent tumors responded well and achieved complete regression. Three patients have survived without evidence of local recurrence with a median follow-up time of 34 months. Marginal recurrence was observed at the posterosuperior wall in a patient with adenoid cystic carcinoma at 30 months after SRT. One patient who received SRT after the two complete courses of radiation therapy died 6 months after SRT as a result of rupture of a branch of the left carotid artery, but autopsy revealed no local residual tumor. Conclusions: Stereotactic radiotherapy with isocentric multiportals in one plane, which is changed at every 20 to 30 Gy, can provide local control with acceptable toxicity in patients with recurrent nasopharyngeal carcinoma, but increased clinical experience and longer follow-up will be necessary to evaluate the overall role of this technique in nasopharyngeal carcinoma. [ABSTRACT FROM AUTHOR]

Background Purpose Methods Results Conclusions Comprehensive quality assurance (QA) for a seamless workflow of high‐dose‐rate brachytherapy, from imaging to planning and irradiation, is uncommon, and QA of the source dwell position is performed in one‐ or two‐dimensions. Gel dosimetry using magnetic resonance imaging (MRI) is effective in verifying the three‐dimensional distribution of doses for image‐guided brachytherapy (IGBT). However, MRI scanners are not readily accessible, and MRI scanning is time‐consuming. Nevertheless, X‐ray computed tomography (XCT) is available for IGBT planning.In this study, we designed and developed an efficient method for QA for a seamless workflow of IGBT with a new commercially available XCT‐based polymer gel dosimeter.To enable direct insertion of brachytherapy applicators, the gelatinizing agent of the dosimeter was modified. A cylindrical polyvinyl chloride jar was filled with the modified gel dosimeter, which was subsequently used to determine the reproducibility of source dwell positions, detectability of source positional errors from intentionally introduced catheter length offsets, effect of looped source transfer tubes on the average displacement, extent of inter‐observer variation, and gel robustness following multiple needle‐insertions. Three ProGuide sharp needles were inserted into the jar. The dwell time at each point was determined to identify the irradiated volume with a diameter of approximately 10 mm on XCT images. All the times were the same. The plan was delivered using an afterloader with an Ir‐192 radioactive source, and the irradiated gel dosimeter was scanned using an XCT scanner. The subtracted images were generated from pre‐ and post‐irradiated images. Volumes with incremented Hounsfield units were manually identified and contoured. The centroid of the volume was defined as the measured source dwell position. Subsequently, planned source dwell positions were extracted from the DICOM file of the plan. Finally, the source dwell positions in plan and irradiated gel were compared in three axes.The hardness of the dosimeter was 1250% greater than that of the previously reported gel dosimeter. Source dwell positions were visually identified in the XCT image. Testing of CT acquisition, planning, irradiation, and analysis was completed in approximately 1 h. In the reproducibility test of source dwell positions, created by inserting three needles (each with three source dwell positions), the average displacements of the source positions from the first source dwell position were within 0.5 mm in all three directions. In the detectability test, displacements were less than 1 mm in the x–y plane but greater than 1 mm in the z‐axis, which was the source path direction. When errors of 1–3 mm were intentionally introduced, the measured displacement was within 0.7 mm of the median (range: 0.21–1.65 mm) of intentional errors. When the transfer tube was looped, the source dwell position displaced by approximately 1 mm. After 20 needle‐insertions, the source dwell position displacement was within 1 mm. The maximum inter‐observer variation of contouring was 0.57 mm.The XCT‐based gel dosimeter enabled verification of three‐dimensional source dwell positions for a seamless workflow of IGBT with high precision and efficiency. [ABSTRACT FROM AUTHOR]

From 1975 to 1990, 72 patients with T1 glottic cancer, excluding a verrucous type of carcinoma, were treated with radiation therapy (RT). All treatments were given with a standard fractionation of 2 Gy per day. The total dose to the tumor ranged from 60 to 70 Gy. Six patients received a split-course RT. The overall local control rate was 87% at 5 years. Forty-one patients who completed RT in 45 days or less had a 5-year local control rate of 95%. Sixteen patients who completed a treatment course in 46 to 49 days had a local control rate of 81%. Fifteen patients with a treatment course of more than 50 days had a local control rate of 73%. There was a statistically significant difference in local control rates among the three groups (P<.05). The split-course RT group had a 5-year local control rate of 50%; that rate was statistically significantly inferior to that of the continuous course group ( P<.001). Multivariate analysis also showed that an interruption of the treatment course was an important parameter in relation to the local control. The prolongation of standard RT schedules adversely affected local control of T1 glottic carcinoma and, therefore, should be avoided whenever possible. [ABSTRACT FROM AUTHOR]