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Background: Human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) is defined by p16 positivity and/or HPV DNA positivity. Because survival of patients with HPV-related OPSCC after chemoradiotherapy is favorable, a de-intensified treatment is expected to lead to less morbidity while maintaining low mortality. The association of tumor p16 and HPV DNA status with survival after radiotherapy alone remains unknown., Methods: We retrospectively examined survival of 107 patients with locally advanced OPSCC after radiotherapy alone (n = 43) or chemoradiotherapy (n = 64) with respect to tumor p16 and HPV DNA status, using Cox's proportional hazard model., Results: Survival after radiotherapy alone was significantly worse in p16-positive/HPV DNA-negative locally advanced OPSCC than in p16-positive/HPV DNA-positive locally advanced OPSCC. In bivariable analyses that included T category, N category, TNM stage, and smoking history, the survival disadvantage of p16-positive/HPV DNA-negative locally advanced OPSCC remained significant. There was no significant difference in survival after chemoradiotherapy between p16-positive/HPV DNA-positive locally advanced OPSCC and p16-positive/HPV DNA-negative locally advanced OPSCC. Survival in p16-positive/HPV DNA-positive locally advanced OPSCC after radiotherapy alone was similar to that after chemoradiotherapy, which stayed unchanged in bivariable analyses after adjustment of every other covariable. Survival of p16-negative/HPV DNA-negative locally advanced OPSCC was poor irrespective of treatment modality., Conclusions: Survival in p16-positive locally advanced OPSCC differs depending on HPV DNA status. Radiotherapy alone can serve as a de-intensified treatment for p16-positive/HPV DNA-positive locally advanced OPSCC, but not for p16-positive/HPV DNA-negative locally advanced OPSCC.

Objective: The first revision of "Japanese Clinical Practice Guideline for Head and Neck Cancer" was made in 2013 by the clinical practice guideline committee of Japan Society for Head and Neck Cancer, in response to the revision of the TNM classification., Methods: 34 CQs (Clinical Questions) were newly adopted to describe the diagnosis and treatment methods currently considered most appropriate, and offered recommendation grade made by the consensus of the committee. A comprehensive literature search was performed for studies published between 2001 and 2012 using PubMed. Qualified studies were analyzed and the results were evaluated, consolidated and codified by all the committee members., Results: Elective neck dissection (ND) does contribute to improvement in survival and should be performed for patients with high-risk tongue cancer. At present, no research has clearly demonstrated the utility of superselective arterial infusion chemotherapy. However, depending on the site and stage of the cancer, combination with radiotherapy may be useful for preserving organ function or improving survival rate. Concurrent CDDP chemotherapy and adjuvant radiotherapy contributes to improvement of survival rate as an adjuvant therapy for advanced squamous cell carcinoma of the head and neck in patients at high risk of recurrence. The anti-EGFR antibody cetuximab (Cmab) has an additive effect with radiotherapy. However, the indication must be carefully considered since this treatment has not been compared with the standard treatment of chemoradiotherapy. Cmab has been shown to have an additive effect with chemotherapy (CDDP/5-FU) in patients with unresectable metastatic or recurrent cancer. Preoperative and postoperative oral care may reduce the risk of postoperative complications such as surgical wound infection and pneumonia in head and neck cancers. Rehabilitation soon after ND for cervical lymph node metastasis is recommended for maintaining and restoring shoulder function., Conclusions: In this article, we described most relevant guidelines and CQs for the diagnosis and treatment of head and neck cancer in Japan. These guidelines are not intended to govern therapies that are not shown here, but rather aim to be used as a guide in searching for the most appropriate treatment for individual patient., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: To evaluate the efficacy and safety of alternating chemoradiotherapy (ACRT) with early assessment of advanced laryngeal cancer., Methods: Patients with stage III or IV glottic or supraglottic squamous cell carcinoma were enrolled. ACRT consisted of two cycles of chemotherapy involving 5-fluorouracil and cisplatin (weeks 1 and 6) and radiotherapy (RT; weeks 2 and 7) administered alternately. An early assessment was performed after one cycle of chemotherapy and RT. Patients with a partial response (PR) or a complete response at early assessment continued ACRT. Patients with stable disease (SD) or progressive disease at early assessment discontinued ACRT and underwent salvage surgery. After completion of ACRT, patients who had residual primary tumor and lymph metastasis underwent salvage surgery., Results: Twenty-eight patients were enrolled in this trial. Median follow-up was 60.0 months. After each cycle of chemotherapy and RT, 24 of the 28 patients (85.7%) were assessed as having a PR at early assessment and continued ACRT, and 4 of 28 patients (14.3%) who were assessed as having SD at early assessment discontinued ACRT and underwent salvage surgery. The estimated 5-year local control and 5-year survival rates were 49.0% and 77.4%, respectively. Larynx preservation was achieved in 17 patients. The estimated 5-year laryngeal preservation rate was 59.4%. Major toxicity included nausea, stomatitis, dermatitis, dysphagia and hemoglobin toxicity. Grade 3 or 4 stomatitis occurred in three patients (10.7%)., Conclusion: The clinical results of ACRT with early assessment of advanced laryngeal cancer patients showed sufficient efficacy and safety., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Objective: This study was designed to investigate the value of preoperative thallium-201 (201Tl) SPECT as a predictor of outcome in malignant glioma., Methods: From January 1990 to September 2003, 109 patients with glioma were treated with postoperative radiotherapy. Of these, 36 patients with malignant gliomas who underwent preoperative 201Tl-SPECT were included in this study (grade 3: n=14, grade 4: n=22). On early (10 minutes) and delayed (2 hours) images after 111 MBq 201TlCl injection, we calculated radioactivity ratios of tumors to contralateral normal brain (T/N ratios) and retention indices (RIs). For early and delayed images, we compared outcome between a high T/N ratio group (T/N ratio equal or greater than the average) and a low T/N ratio group (T/N ratio less than the average). We also divided the patients into two groups on the basis of RI; a high RI group (RI equal or greater than the average) and a low RI group (RI less than the average), and similarly compared outcome between the two groups., Results: Median survival time was 12 months for both grade 3 and grade 4 tumors; however, two-year survival was 53% for grade 3 and 15% for grade 4. In both early and delayed images, outcome was significantly better for patients with low T/N ratios (early < 4.71, delayed < 3.96) than those with high T/N ratios (early: p = 0.030, delayed: p = 0.049). However, no significant survival difference was apparent between the low- (< -12.25) and high RI groups. In grade 3 glioma, patients with high T/N ratios demonstrated a tendency toward poorer outcome, although this trend was not significant (early: p = 0.079, delayed: p = 0.099). Overall outcome was poor for grade 4 glioma, and the difference in survival between low and high T/N ratio groups was not significant (early: p = 0.51, delayed: p = 0.53). However, long survival was seen only in patients with lower T/N ratios., Conclusions: Differences of 201Tl uptake in malignant gliomas could predict outcome. 201Tl-SPECT is potentially useful in the management of patients with malignant gliomas.

"Flare" phenomenon has been primarily reported as a transient increase in the number or intensity of lesions on bone scans in patients receiving hormonal or chemotherapy. It has been well documented in patients with metastatic breast or prostate carcinoma, and recently reported in those with lung cancer. We present a case of bone metastasis from bladder carcinoma, in which healing flare phenomenon was observed after radiotherapy.

Background and Aim: Effective treatment of lesions that develop in the irradiated area of head and neck squamous cell carcinoma is a major concern. This study aimed to clarify the efficacy and safety of endoscopic resection for such lesions. Methods: Among consecutive patients who underwent endoscopic resection for histologically proven head and neck squamous cell carcinoma between January 2014 and December 2021, those who received definitive radiotherapy/chemoradiotherapy before endoscopic resection were included in this single‐center, retrospective study. Short‐ and long‐term outcomes were evaluated. Results: Among 422 patients who underwent endoscopic resection for 615 lesions, 43 patients with 57 lesions were eligible. All 57 lesions were treated with endoscopic submucosal dissection and en bloc resection was achieved in all lesions. Grade 3 of Common Toxicity Criteria for Adverse Events v5.0 occurred in eight (19%) patients (dysphagia, seven; stricture, three; aspiration pneumonia, two; and pharyngeal necrosis, one [some cases overlapped]), but no grade ≥ 4 events occurred. Enteral nutrition by gastrostomy was temporarily required in two patients owing to dysphagia and laryngeal necrosis. During the median follow‐up of 40 (interquartile range, 29.5–61) months after endoscopic submucosal dissection for the lesions developed in the irradiated area, local recurrence and metachronous lesions developed in two (5%) and nine (21%) patients, respectively. However, total laryngectomies and tracheostomies were avoided in all patients. The 3‐year overall and disease‐specific survivals were 81% (95% confidence interval, 64%–91%) and 94% (95% confidence interval, 79%–99%), respectively. Conclusions: Favorable local control and safety of endoscopic submucosal dissection were demonstrated. [ABSTRACT FROM AUTHOR]

Optimal regimens using recent radiotherapy (RT) equipment for bleeding gastric cancer (GC) have not been fully investigated yet. We retrospectively reviewed the clinical data of 20 patients who received RT for bleeding GC in our institution between 2016 and 2021. Three-dimensional conformal RT was performed. The effectiveness of RT was evaluated by the mean serum hemoglobin (Hb) level and the number of transfused red blood cell (RBC) units 1 month before and after RT. The median first radiation dose was a BED of 39.9 Gy. The treatment success rate was 95% and the rebleeding rate was 10.5%. There was a significant increase in the mean Hb level (8.0 ± 1.1 vs. 9.8 ± 1.3 g/dL, p = 0.01), and a significant decrease in the mean number of transfused RBC units (6.8 ± 3.3 vs. 0.6 ± 1.5 units, p < 0.01). Severe toxicity was observed in two patients (anorexia [n = 1] and gastrointestinal [GI] perforation [n = 1]). Reirradiation was attempted in three patients (for hemostasis [n = 2] and for mass reduction [n = 1]). The retreatment success rate for rebleeding was 100%. GI perforation occurred in two patients who had received hemostatic reirradiation. Palliative RT for bleeding GC using recent technology had excellent efficacy. However, it may be associated with a risk of GI perforation. [ABSTRACT FROM AUTHOR]

Background. The purpose was to estimate retrospectively the outcome of patients with musculoskeletal sarcoma or malignant lymphoma treated with intraoperative radiotherapy (IORT). Methods. Between 1988 and 1999, definitive IORT in combination with surgical excision was performed in 24 patients with musculoskeletal sarcoma (malignant fibrous histiocytoma, 10; osteosarcoma, 6; liposarcoma, 2; chondrosarcoma, 1; synovial sarcoma, 1; Ewing's sarcoma, 1; angiosarcoma, 1; epithelioid sarcoma, 1; malignant schwannoma, 1) and 3 patients with malignant lymphoma. The tumor was excised by marginal margin excision, intralesional margin excision, or wide margin excision; 15–45Gy electrons was then delivered to the affected sites. Results. In the 8 patients without distant metastases at the first visit, 4 patients are alive 6.5–11.5 years after IORT, and 4 patients died <4.5 years after IORT. The incidence of local recurrence was 13%. In the 19 patients with distant metastases at the first visit, 3 patients are alive 2.5–6.7 years after IORT, and 16 patients died 0.2–5.7 years after IORT. The incidence of local recurrence was 45%. Complications after IORT were found in 5 patients: neuropathy, 1 patient; skin necrosis, 1 patient; myelopathy, 1 patient; enteritis ileus, 1 patient; and edema, 1 patient. Conclusion. IORT with a radiation dose of 15–45Gy in combination with surgical excision appeared to be useful for local control and to be more effective in patients without distant metastases at the first visit than in patients with distant metastases. [ABSTRACT FROM AUTHOR]

• Secondary analysis related to hypothyroidism (HT) in JCOG1008. • This is a HT report in a prospective study of postoperative chemoradiotherapy for head and neck cancer (HNC) patient. • In total, 16.7 % patients developed HT within 2 years after radiotherapy. • Weekly cisplatin using intensity-modulated radiotherapy was a HT factor. • V 60Gy potentially associated with the development of HT by intensity modulated radiation therapy. Hypothyroidism is a recognized late adverse event following radiotherapy for head and neck cancer (HNC). In the JCOG1008 trial, we treated patients with high-risk HNC with postoperative chemoradiotherapy. We aimed to elucidate factors associated with hypothyroidism by analyzing the JCOG1008 data. In 2012–2018, 261 patients from 28 institutions were enrolled in JCOG1008. Thyroid function tests were conducted to assess hypothyroidism, including free thyroxine (FT4) and thyroid-stimulating hormone assays. Hypothyroidism was defined as Grade 2 or higher in CTCAE v4.0. Various clinical and dosimetric parameters were analyzed. In radiotherapy, there were no dose constraints for the thyroid. Multivariable analysis was conducted on these variables to identify predictive factors for hypothyroidism. The analysis included 162 patients (57 with 3D-CRT and 105 with IMRT), with a median follow-up of 4.7 years (0.3–9.3 years). Among these, 27 (16.7 %) developed hypothyroidism within 2 years after radiotherapy. In a multivariable analysis, the weekly cisplatin [OR=7.700 (CI: 1.632–36.343, p = 0.010)] and baseline FT4 [OR=0.009 (CI: <0.001–0.313, p = 0.010)] were significantly associated with hypothyroidism in the IMRT group. Regarding dosimetric characteristics, V 60Gy [OR=1.069 (CI: 0.999–1.143, p = 0.054)] was potentially associated with the development of hypothyroidism. The study revealed that the incidence of hypothyroidism within 2 years after postoperative chemoradiotherapy for high-risk HNC was 16.7 % based on analytical results from prospective clinical trials. [ABSTRACT FROM AUTHOR]

Purpose: Human papillomavirus (HPV)-related squamous cell carcinoma of the oropharynx (OPSCC) is extremely radiosensitive. Radiation therapy plus high-dose cisplatin remains the standard of care but causes long-term toxicity. Treatment deintensification approaches that reduce toxicity while maintaining survival are desirable for HPV-related OPSCC.Methods and Materials: We conducted a single-arm, multicenter, phase 2 trial. Patients with newly diagnosed, biopsy-proven, American Joint Committee on Cancer (seventh edition) stage III or IV OPSCC positive for both p16 and HPV DNA were eligible. Patients with T4, N3, or T1N1 disease were excluded. Smoking history was not included in eligibility criteria. Patients received intensity modulated radiation therapy (IMRT) of 70 Gy in 35 fractions or 70.4 Gy in 32 fractions without chemotherapy. The primary endpoint was complete response or complete metabolic response 10 weeks after IMRT completion.Results: Between September 13, 2013, and November 15, 2016, 39 patients were enrolled according to a 2-stage Simon design. Twenty-three patients (59%) had smoked for more than10 pack-years. Thirty-six patients (92%) had tumors genotyped as HPV16. Thirty-seven patients (95%) received full-dose radiation therapy and 35 (90%) had complete response or complete metabolic response. Median follow-up was 51 months (interquartile range, 41-63 months). One patient (3%) had regional recurrence and 3 (8%) had distant metastasis. One patient died of disease. The 2-year progression-free survival rate was 94% (95% CI, 81%-99%), and the 2-year overall survival rate was 100%. Common grade 3 adverse events during IMRT included mucositis in 10 patients (26%) and dysphagia in 7 patients (18%). No patients were dependent on a feeding tube at 1 month after IMRT completion. No grade 3 or 4 late adverse events were observed.Conclusions: IMRT alone is associated with excellent response as well as reduced toxicity and could be a treatment option for carefully selected patients with locally advanced "true" HPV-related OPSCC. Further studies are warranted. [ABSTRACT FROM AUTHOR]

Highlights • The tube feeding dependence was lower than expected by the original NTCP model. • The closed testing procedure indicated that adjustment of the intercept was needed. • The oral tongue could be new organ at risk for tube feeding dependence. Abstract Background and purpose The purpose of this study was to externally validate a previously published normal tissue complication probability (NTCP) model for tube feeding dependence at 6 months (TUBE M6) after completion of (chemo) radiotherapy. Materials and methods This study evaluated 122 head and neck cancer patients treated by definitive (chemo) radiotherapy. The closed testing procedure was used to select the appropriate method for updating the NTCP model. In this procedure, the likelihood ratio test was used to compare the updated model against the original model. Results Mean predicted NTCP was 12.2% (95% CI: 9.9%–14.5%) when using the original NTCP model for TUBE M6. TUBE M6 at our institute was 5.7% (95% CI: 1.8–9.6%) for the 122 patients evaluated. The test for the model revision against the original NTCP model was statistically significant (p = 0.032). The test for the model revision against the model adjusting intercept only was not statistically significant (p = 0.240). According to the closed testing procedure, the model required adjusting the intercept only. Conclusions TUBE M6 at our institute was lower than that predicted by the original NTCP model. The closed testing procedure indicated that only an adjustment of the intercept was needed indicating the importance of external validation. [ABSTRACT FROM AUTHOR]

Purpose: Results of radiation therapy for primary central nervous system lymphoma (PCNSL) were poor in the 1970–1980s, with most reported 5-year survival rates being less than 10%. To investigate whether the prognosis of PCNSL patients treated by radiation alone remains still poor, we investigated the results of radiation monotherapy in the 1990s. Methods and Materials: We collected data on 132 patients with histologically proven PCNSL treated by radiation alone in the 1990s from three nationwide or regional multiinstitutional studies conducted by the Japanese Society for Therapeutic Radiology and Oncology (JASTRO) Lymphoma Study Group or the Chubu Radiation Oncology Group. Follow-up data were updated as far as possible. Eleven patients who did not complete planned radiotherapy were included. The data were analyzed in relation to patient and tumor characteristics. The median patient age was 63 years, and the World Health Organization performance status (PS) was 3 or 4 in 40% of the patients. Multiple tumors were seen in 34%. Whole-brain irradiation with or without focal boost was used in 92%. The median radiation dose to the tumor site was 50 Gy (range, 8–74 Gy). Results: For all 132 patients, the median survival time was 18 months and the 5-year survival rate was 18.0%. For 62 patients with PS 0–3 and aged 16–65 years (i.e., those eligible for the European Organization for Research and Treatment of Cancer 20962 study), the median survival was 26 months and 5-year survival was 24%. The 5-year survival was 25% for patients 63 years old or younger, and 9.8% for those older than 63 years (p = 0.0005). The 5-year survival was 22% for patients with PS 0–2 and 13% for those with PS 3 or 4 (p = 0.0040). Multivariate analysis confirmed the negative influence of higher age on patient prognosis. Conclusions: The results of radiation monotherapy for PCNSL appear to have improved as compared with those reported previously. The results of new treatment should be evaluated in light of this finding. Since most prospective studies on the combined treatment exclude poor PS and high-age patients, the 5-year survival rate of 30% may not be regarded as a marked improvement over radiation alone. [Copyright &y& Elsevier]

Purpose: To analyze the outcome in T1–2 hypopharyngeal cancer (HPC) patients treated with definitive radiotherapy (RT). Patients and Methods: A total of 103 patients with T1–2 hypopharyngeal squamous cell carcinoma treated with radical RT between March 2000 and June 2008 at our institution were analyzed. Pre-RT neck dissection (ND) was performed in 26 patients with advanced neck disease. Chemotherapy was used concurrently with RT in 14 patients. Sixty patients were associated with synchronous or metachronous malignancies. The median follow-up for surviving patients was 41 months. Results: The 3-year overall and cause-specific survival rates were 70% and 79%, respectively. The 3-year local control rates were 87% for T1 and 83% for T2 disease. The ultimate local control rate was 89%, including 7 patients in whom salvage was successful. The ultimate local control rate with laryngeal preservation was 82%. Tumors of the medial wall of the pyriform sinus tended to have lower control rates compared with tumors of the lateral or posterior pharyngeal wall. Among patients with N2b–3 disease, the 3-year regional control rates were 74% for patients with pre-RT ND and 40% for patients without ND. The 3-year locoregional control rates were as follows: Stage I, 100%; Stage II, 84%; Stage III, 67%; Stage IVA, 43%; Stage IVB, 67%. Forty-two patients developed disease recurrence, with 29 (70%) patients developing recurrence within the first year. Of the 103 patients, 6 developed late complications higher than or equal to Grade 3. Conclusions: Definitive RT accomplished a satisfactory local control rate and contributed to organ preservation. [ABSTRACT FROM AUTHOR]