Re-irradiation with interstitial brachytherapy in uterine cancer patients with vaginal recurrence after post-operative pelvic irradiation.

PURPOSE: This study aimed to evaluate the outcomes and dose-volume parameters of re-irradiation with interstitial brachytherapy (ISBT) in uterine cancer patients with vaginal recurrence after post-operative pelvic irradiation. MATERIAL AND METHODS: We evaluated six uterine cancer patients who received re-irradiation with ISBT between January, 2012 and December, 2016. As an initial treatment, all patients received post-operative whole pelvic irradiation of 45-50.4 Gy in 25-28 fractions. For vaginal recurrence, all patients were treated with ISBT alone at a dose of 38-42 Gy in 6-7 fractions for clinical target volumes (CTVs) for 3-4 days. RESULTS: Post-operative pelvic irradiation was delivered to five and one patients, using a three-dimensional conformal technique and intensity-modulated radiotherapy, respectively. Median duration from surgery to vaginal recurrence was 25.7 months. Median tumor size just before ISBT was 3.3 cm. Median time from completion of pelvic irradiation to ISBT initiation was 24.1 months. Mean doses per fraction of ISBT for CTV D90 (the minimum dose received by 90% of CTV) and minimum dose received by 2cc (D2cc) for the bladder and for rectum were 6.1 Gy, 4.4 Gy, and 3.8 Gy, respectively. Mean total equivalent dose in 2 Gy fractions (EQD2), including external beam radiotherapy and ISBT, for D2cc for the bladder, sigmoid, and rectum were 92.1 Gy, 50.4 Gy, and 81.6 Gy, respectively. Median follow-up duration was 53.3 months. Local recurrence was observed in two patients, and four of the six patients were alive. Grade 2 late rectal complications occurred in two patients, and no late grade ≥ 3 complications were observed in four alive patients. CONCLUSIONS: Re-irradiation with ISBT may be an effective treatment strategy for gynecological cancer patients with vaginal recurrence after post-operative pelvic irradiation.

Risk factor of pneumonitis on dose-volume relationship for chemoradiotherapy with durvalumab: Multi-institutional research in Japan.

OBJECTIVES: To estimate appropriate dose-volume parameters for avoidance of pneumonitis in use of chemoradiotherapy and durvalumab for treatment of lung cancer. MATERIALS AND METHODS: Patients with non-small cell lung cancer treated with concurrent chemoradiotherapy followed by durvalumab at 9 centers were enrolled in the study. Three-dimensional radiotherapy, intensity modulated radiotherapy, and proton beam therapy were used. The frequency and severity of pneumonitis and the dose-volume relationship for normal lung were evaluated. Univariable and multivariable analyses were conducted to identify risk factors. A covariate adjusted hazard ratio was then estimated for the percentages of normal lung volume irradiated at ≥ X Gy (Vx) (X = 5-40) and lung volume non-irradiated at ≥ X Gy (X = 5-40), with the covariates selected in the variable selection. Cumulative incidence functions and covariate adjusted hazard ratios were also estimated for dichotomized variables, with estimated cut-off points. RESULTS: A total of 91 patients were enrolled in the study. The median time from the start of radiotherapy to development of pneumonitis was 4.1 months. Pneumonitis was observed in 80 patients (88%), including grade 2 or severe pneumonitis in 31 (34%) and ≥ grade 3 pneumonitis in 11 (12%). Pneumonitis was inside the irradiation field in 73 of the 80 patients (91%). The selected factors for ≥ grade 2 pneumonitis were V20, and primary site (upper lobe) in multivariable analysis. The cut off value of V20 was 18.99%, and there was a significant difference between V20 of < 18.77 and ≥ 18.77. CONCLUSION: Though there are some limitation of this study, the basic concept of concurrent chemoradiotherapy with an emphasis on V20 remains unchanged in use of durvalumab. However, we recommend reduction of V20 to as small a value as possible in use of this therapy.

A multi-institutional survey of the quality of life after treatment for uterine cervical cancer: a comparison between radical radiotherapy and surgery in Japan.

This study aimed to research the post-treatment quality of life (QOL) between radiotherapy (RT)- and operation (OP)-treated early cervical cancer survivors, using separate questionnaires for physicians and patients. We administered an observational questionnaire to patients aged 20-70 years old with Stages IB1-IIB cervical cancer who had undergone RT or OP and without recurrence as outpatients for ≥6 months after treatment. We divided 100 registered patients equally into two treatment groups (n = 50 each). The average age was 53 and 44 years in the RT and OP groups, respectively. The RT group included 34 and 66% Stage I and II patients, respectively, whereas the OP group included 66 and 34% Stage I and II patients, respectively. The OP group included 58% of patients with postoperative RT. Combination chemotherapy was performed in 84 and 48% of patients in the RT and OP groups, respectively. On the physicians' questionnaire, we observed significant differences in bone marrow suppression (RT) and leg edema (OP). On the patients' questionnaire, significantly more patients had dysuria and leg edema in the OP group than in the RT group, and severe (Score 4-5) leg edema was significantly higher in the post-operative RT group than in the OP only group. The frequency of sexual intercourse decreased after treatment in both groups. On the patients' questionnaire, there were no significant differences between the two groups regarding sexual activity. These findings are useful to patients and physicians for shared decision-making in treatment choices. The guidance of everyday life and health information including sexual life after treatment is important.

Proton beam therapy for unresectable intrahepatic cholangiocarcinoma.

BACKGROUND AND AIM: Treatment for unresectable intrahepatic cholangiocarcinoma (ICC) has not been established. The aim of the study was to evaluate the outcome of proton beam therapy (PBT) for patients with unresectable ICC. METHODS: Up to 2010, 20 patients (11 males, 9 females, median age 63 years old) with unresectable ICC (two, seven, seven, and four in stages II, IIIA, IIIC, and IV, respectively) were treated with PBT. The largest dimensions of the tumors ranged from 15 to 140 mm (median: 50 mm). The intrahepatic region and lymph nodes received median total proton doses of 72.6 GyE in 22 fractions and 56.1 GyE in 17 fractions, respectively. Four patients received concurrent chemotherapy (tegafur, gimeracil, and oteracil; TS-1) during PBT. Twelve patients were treated curatively, and eight were treated palliatively because tumors were present outside the irradiation field. RESULTS: In the curative group, nine tumors within the irradiated field were controlled in follow-up of 8.6-62.6 months (median: 20.8 months). Median survival rates in the curative and palliative groups were 27.5 and 9.6 months, respectively, and overall 1- and 3-year survival rates were 82% and 38%, and 50% and 0%, respectively. Eight patients survived for > 2 years, and there was no distant metastasis in five of these patients after 2 years. No severe side-effects occurred. CONCLUSIONS: The results suggest that long-term survival can be achieved using PBT for patients with unresectable ICC without distant metastasis. Further studies are required to determine the optimal treatment schedule and best combination of PBT and chemotherapy.

Outcomes and prognostic factors for recurrence after high-dose proton beam therapy for centrally and peripherally located stage I non--small-cell lung cancer.

INTRODUCTION: This study was conducted to determine disease control rates and prognostic factors associated with recurrence of centrally and peripherally located stage I NSCLC treated using high-dose PBT. PATIENTS AND METHODS: Seventy-four patients with 80 centrally or peripherally located stage I NSCLCs were treated with PBT. A protocol using 72.6 Gy (RBE) in 22 fractions was used for centrally located tumors, and 66 Gy (RBE) in 10 or 12 fractions was used for peripherally located tumors. Data were collected and control rates and prognostic factors for recurrence were evaluated retrospectively. RESULTS: The median follow-up period was 31.0 months. The overall survival, disease-specific survival, and progression-free survival rates were 76.7%, 83.0%, and 58.6% at 3 years, respectively. Disease recurrence was noted in 30 patients and local recurrence of 11 tumors occurred. The 3-year local control rate was 86.2% for stage IA tumors and 67.0% for stage IB tumors. Radiation dose was identified as a significant prognostic factor for disease recurrence and local recurrence. Tumor diameter and age were only significantly associated with disease recurrence. The 3-year local control rate was 63.9% for centrally located tumors irradiated with 72.6 Gy (RBE) and 88.4% for peripherally located tumors irradiated with 66 Gy (RBE). CONCLUSION: Radiation dose was shown to be the most significant prognostic factor for tumor control in stage I NSCLC treated using high-dose PBT. Tumor diameter was not significant for local control. Further evaluation of PBT for centrally located tumors is warranted.

Evaluation of liver function after proton beam therapy for hepatocellular carcinoma.

PURPOSE: Our previous results for treatment of hepatocellular carcinoma with proton beam therapy (PBT) revealed excellent local control. In this study, we focused on the impact of PBT on normal liver function. METHODS AND MATERIALS: The subjects were 259 patients treated with PBT at the University of Tsukuba between January 2001 and December 2007. We evaluated the Child-Pugh score pretreatment, on the final day of PBT, and 6, 12, and 24 months after treatment with PBT. Patients who had disease progression or who died with tumor progression at each evaluation point were excluded from the analysis to rule out an effect of tumor progression. An increase in the Child-Pugh score of 1 or more was defined as an adverse event. RESULTS: Of the 259 patients, 241 had no disease progression on the final day of PBT, and 91 had no progression within 12 months after PBT. In univariate analysis, the percentage volumes of normal liver receiving at least 0, 10, 20, and 30 GyE in PBT (V0, 10, 20, and 30) were significantly associated with an increase of Child-Pugh score at 12 months after PBT. Of the 91 patients evaluated at 12 months, 66 had no increase of Child-Pugh score, 15 had a 1-point increase, and 10 had an increase of ≥2 points. For the Youden index, the optimal cut-offs for V0, V10, V20, and V30 were 30%, 20%, 26%, and 18%, respectively. CONCLUSION: Our findings indicate that liver function after PBT is significantly related to the percentage volume of normal liver that is not irradiated. This suggests that further study of the relationship between liver function and PBT is required.

Results of proton beam therapy without concurrent chemotherapy for patients with unresectable stage III non-small cell lung cancer.

INTRODUCTION: This study was performed retrospectively to evaluate the outcome of patients with stage III non-small cell lung cancer (NSCLC) after proton beam therapy (PBT) alone. METHODS: The subjects were 57 patients with histologically confirmed NSCLC (stage IIIA/IIIB: 24/33) who received PBT without concurrent chemotherapy. The cohort included 32 cases of squamous cell carcinoma, 18 adenocarcinoma, and 7 non-small cell carcinoma. Lymph node metastases were N0 7, N1 5, N2 30, and N3 15. Planned total doses ranged from 50 to 84.5 GyE (median, 74 GyE). RESULTS: Planned treatment was completed in 51 patients (89%). At the time of analysis, 20 patients were alive, and the median follow-up periods were 16.2 months for all patients and 22.2 months for survivors. The median overall survival period was 21.3 months (95% confidence interval: 14.2-28.4 months), and the 1- and 2-year overall survival rates were 65.5% (52.9-78.0%) and 39.4% (25.3-53.5%), respectively. Disease progression occurred in 38 patients, and the 1- and 2-year progression-free survival rates were 36.2% (23.1-49.4%) and 24.9% (12.7-37.2%), respectively. Local recurrence was observed in 13 patients, and the 1- and 2-year local control rates were 79.1% (66.8-91.3%) and 64.1% (47.5-80.7%), respectively. Grade ≥ 3 lung toxicity was seen in six patients, esophageal toxicity occurred at grade ≤ 2, and there was no cardiac toxicity. CONCLUSION: The prognosis of patients with unresectable stage III NSCLC is poor without chemotherapy. Our data suggest that high-dose PBT is beneficial and tolerable for these patients.

Outcome of T4 (International Union Against Cancer Staging System, 7th edition) or recurrent nasal cavity and paranasal sinus carcinoma treated with proton beam.

PURPOSE: To investigate the clinical features, prognostic factors, and toxicity of treatment for unresectable carcinomas of the nasal cavity and paranasal sinus (NCPS) treated with proton beam therapy (PBT). METHODS AND MATERIALS: Seventeen patients (13 men, 4 women) with unresectable carcinomas of the NCPS who underwent PBT at the University of Tsukuba between 2001 and 2007 were analyzed. The patients' median age was 62 years (range, 30-83 years). The tumors were located in the nasal cavity in 3 patients, the frontal sinus in 1, the ethmoid sinus in 9, and the maxillary sinus in 4. The clinical stage was Stage IVA in 5 cases, IVB in 10, and recurrent in 2. The tumors were deemed unresectable for medical reasons in 16 patients and because of refusal at a previous hospital 4 months earlier in 1 patient. All the patients received PBT irradiation dose of 22-82.5 GyE and a total of 72.4-89.6 GyE over 30-64 fractions (median 78 GyE over 36 fractions) with X-ray, with attention not exceeding the delivery of 50 GyE to the optic chiasm and brainstem. RESULTS: The overall survival rate was 47.1% at 2 years and 15.7% at 5 years, and the local control rate was 35.0% at 2 years and 17.5% at 5 years. Invasion of the frontal or sphenoid sinus was a prognostic factor for overall survival or local control. Late toxicity of more than Grade 3 was found in 2 patients (brain necrosis in 1 and ipsilateral blindness in 1); however, no mortal adverse effects were observed. CONCLUSION: Proton beam therapy enabled a reduced irradiation dose to the optic chiasm and brainstem, enabling the safe treatment of unresectable carcinomas in the NCPS. Superior or posterior extension of the tumor influenced patient outcome.