Real-World Results of Stereotactic Body Radiotherapy for 399 Medically Operable Patients with Stage I Histology-Proven Non-Small Cell Lung Cancer.

Surgery is the standard treatment for stage I non-small cell lung cancer (NSCLC); however, no clear randomized trial demonstrates its superiority to stereotactic body radiotherapy (SBRT) regarding survival. We aimed to retrospectively evaluate the treatment outcomes of SBRT in operable patients with stage I NSCLC using a large Japanese multi-institutional database to show real-world outcome. Exactly 399 patients (median age 75 years; 262 males and 137 females) with stage I (IA 292, IB 107) histologically proven NSCLC (adenocarcinoma 267, squamous cell carcinoma 96, others 36) treated at 20 institutions were reviewed. SBRT was prescribed at a total dose of 48-70 Gy in 4-10 fractions. The median follow-up period was 38 months. Local progression-free survival rates were 84.2% in all patients and 86.1% in the T1, 78.6% in T2, 89.2% in adenocarcinoma, and 70.5% in squamous cell subgroups. Overall 3-year survival rates were 77.0% in all patients: 90.7% in females, 69.6% in males, and 41.2% in patients with pulmonary interstitial changes. Fatal radiation pneumonitis was observed in two patients, all of whom had pulmonary interstitial changes. This real-world evidence will be useful in shared decision-making for optimal treatment, including SBRT for operable stage I NSCLC, particularly in older patients.

Comparative Analysis of Photon Stereotactic Radiotherapy and Carbon-Ion Radiotherapy for Elderly Patients with Stage I Non-Small-Cell Lung Cancer: A Multicenter Retrospective Study.

The emergence of an aging society and technological advances have made radiotherapy, especially stereotactic body radiotherapy (SBRT), a common alternative to surgery for elderly patients with early stage non-small-cell lung cancer (NSCLC). Carbon-ion radiotherapy (CIRT) is also an attractive treatment option with potentially lower toxicity for elderly patients with comorbidities. We compared the clinical outcomes of the two modalities using Japanese multicenter data. SBRT (n = 420) and single-fraction CIRT (n = 70) data for patients with stage I NSCLC from 20 centers were retrospectively analyzed. Contiguous patients ≥ 80 years of age were enrolled, and overall survival (OS), disease-specific survival (DSS), local control (LC), and adverse event rates were compared. The median age was 83 years in both groups and the median follow-up periods were 28.5 and 42.7 months for SBRT and CIRT, respectively. The 3-year OS, DSS, and LC rates were 76.0% vs. 72.3% (p = 0.21), 87.5% vs. 81.6% (p = 0.46), and 79.2% vs. 78.2% (p = 0.87), respectively, for the SBRT vs. CIRT groups. Regarding toxicity, 2.9% of the SBRT group developed grade ≥ 3 radiation pneumonitis, whereas none of the CIRT group developed grade ≥ 2 radiation pneumonitis. SBRT and CIRT in elderly patients showed similar survival and LC rates, although CIRT was associated with less severe radiation pneumonitis.

Stereotactic Radiosurgery for Lung Cancer with a Risk-Adapted Strategy Using the Volumetric Modulated Arc Therapy Technique: A Single Arm Phase II Study.

PURPOSE: A phase II study carried out to assess the efficacy of a risk-adapted strategy of stereotactic radiosurgery (SRS) for lung cancer. The primary endpoint was 3-year local recurrence, and the secondary endpoints were overall survival (OS), disease-free survival (DFS), rate of start of systemic therapy or best supportive care (SST-BSC), and toxicity. MATERIALS AND METHODS: Eligible patients fulfilled the following criteria: performance status of 2 or less, forced expiratory volume in 1 s of 700 mL or more, and tumor not located in central or attached to the chest wall. Twenty-eight Gy was prescribed for primary lung cancers with diameters of 3 cm or less and 30 Gy was prescribed for primary lung cancers with diameters of 3.1-5.0 cm or solitary metastatic lung cancer diameters of 5 cm or less. RESULTS: Twenty-one patients were analyzed. The patients included 7 patients with adenocarcinoma, 2 patients with squamous cell carcinoma, 1 patient with metastasis, and 11 patients with clinical diagnosis. The median tumor diameter was 1.9 cm. SRS was prescribed at 28 Gy for 18 tumors and 30 Gy for 3 tumors. During the median follow-up period of 38.9 months for survivors, 1 patient had local recurrence, 7 patients had regional or distant metastasis, and 5 patients died. The 3-year local recurrence, SST-BSC, DFS, and OS rates were 5.3% (95% confidence interval [CI]: 0.3-22.2%), 20.1% (95% CI: 6.0-40.2%), 59.2% (95% CI: 34.4-77.3%), and 78.2% (95% CI: 51.4-91.3%), respectively. The 95% CI upper value of local recurrence was lower than the null local recurrence probability. There was no severe toxicity, and grade 2 radiation pneumonitis occurred in 1 patient. CONCLUSIONS: Patients who received SRS for lung cancer had a low rate of 3-year local recurrence and tolerable toxicity.

Durvalumab after chemoradiotherapy for locally advanced non-small cell lung cancer prolonged distant metastasis-free survival, progression-free survival and overall survival in clinical practice.

BACKGROUND: In clinical practice, the effect of durvalumab and radiation pneumonitis (RP) on survival after intensity-modulated radiotherapy (IMRT) is not fully understood. The purpose of this retrospective study was to investigate factors related to distant metastasis-free survival (DMFS), progression-free survival (PFS) and overall survival (OS) after IMRT for locally advanced non-small cell lung cancer (LA-NSCLC). METHODS: All patients who were treated with conventional fractionated IMRT for LA-NSCLC between April 2016 and March 2021 were eligible. Time-to-event data were assessed by using the Kaplan-Meier estimator, and the Cox proportional hazards model was used for prognostic factor analyses. Factors that emerged after the start of IMRT, such as durvalumab administration or the development of RP, were analysed as time-dependent covariates. RESULTS: A total of 68 consecutive patients treated with conventional fractionated IMRT for LA-NSCLC were analysed. Sixty-six patients completed radiotherapy, 50 patients received concurrent chemotherapy, and 36 patients received adjuvant durvalumab. During the median follow-up period of 14.3 months, 23 patients died, and tumour progression occurred in 37 patients, including 28 patients with distant metastases. The 1-year DMFS rate, PFS rate and OS rate were 59.9%, 48.7% and 84.2%, respectively. Grade 2 RP occurred in 16 patients, grade 3 in 6 patients and grade 5 in 1 patient. The 1-year cumulative incidences of grade 2 or higher RP and grade 3 or higher RP were 33.8% and 10.3%, respectively. The results of multivariate analyses showed that durvalumab had a significantly lower hazard ratio (HR) for DMFS, PFS and OS (HR 0.31, p < 0.01; HR 0.33, p < 0.01 and HR 0.32, p = 0.02), respectively. Grade 2 or higher RP showed significance for DMFS and a nonsignificant trend for OS (HR 2.28, p = 0.04 and HR 2.12, p = 0.13), respectively, whereas a higher percentage of lung volume receiving 20 Gy or higher was significant for PFS (HR 2.25, p = 0.01). CONCLUSIONS: In clinical practice, durvalumab administration following IMRT with concomitant chemotherapy showed a significant survival benefit. Reducing the risk of grade 2 or higher RP would also be beneficial.

Clinical predictors of severe late urinary toxicity after curative intensity-modulated radiation therapy for localized prostate cancer.

Intractable late urinary toxicity is a serious complication after radiotherapy for patients with localized prostate cancer (LPC). We assessed clinical factors correlated with severe late urinary toxicity in LPC treated with curative image-guided intensity-modulated radiation therapy (IMRT). A total of 452 patients with LPC treated with IMRT between 2002 and 2016 were retrospectively analyzed. Among them, 432 patients received androgen deprivation therapy (ADT). The median total irradiated doses were 80 (range, 76-80) Gy. Each daily dose was 2 Gy per fraction. The median follow-up was 83 (range, 4-210) months. Late urinary toxicity was scored according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.03. Grade 3 late urinary toxicity was observed in 27 patients. No cases with grade ≥ 4 late urinary toxicity were observed. The 5-, 10-, and 12.5-year grade 3 late urinary toxicity-free survival rates were 97%, 91.8% and 88.1%, respectively. Age, risk classification, total irradiated dose, ADT duration, antithrombotic therapy (AT), cardiovascular disease, hypertension (HT), diabetes mellitus (DM), dyslipidemia (DL), prior transurethral resection of the prostate (TURP) and prior high-intensity focused ultrasound (HIFU) were investigated for correlations with grade 3 late urinary toxicity. In univariate analysis, AT and prior HIFU and no other studied factors, were correlated with grade 3 late urinary toxicity. AT and prior HIFU appear to be predictive of grade 3 late urinary toxicity. Patients with LPC with these relevant clinical factors should be carefully followed up by sharing detailed information with the urology department.

Stereotactic body radiotherapy for kidney cancer: a 10-year experience from a single institute.

The purpose of this retrospective study was to investigate survival outcomes and irradiated tumor control (local control [LC]) and locoregional control (LRC) after stereotactic body radiotherapy (SBRT) for T1 or recurrent T1 (rT1) kidney cancer. Twenty-nine nonconsecutive patients with 30 tumors were included. SBRT doses of 70 Gy, 60 Gy or 50 Gy in 10 fractions were prescribed with a linear accelerator using daily image guidance. The Kaplan-Meier method was used to estimate time-to-event outcomes, and the log-rank test was used to compare survival curves between groups divided by each possible factor. The median follow-up periods for all patients and survivors were 57 months and 69.6 months, respectively. The five-year LC rate, LRC rate, progression-free survival (PFS) rate, disease-specific survival (DSS) rate and overall survival (OS) rate were 94%, 88%, 50%, 96% and 68%, respectively. No significant factor was related to OS and PFS. Three of 24 non-hemodialysis (HD) patients had new-onset-HD because of the progression of underlying kidney disease. Grade 3 or higher toxicities from SBRT did not occur. In conclusion, SBRT for kidney cancer provided a high rate of LC, LRC and DSS with minimal toxicities, but patient selection and indication for SBRT should be done carefully considering the relatively low OS rate.

Randomized phase II trial of uracil/tegafur and cisplatin versus pemetrexed and cisplatin with concurrent thoracic radiotherapy for locally advanced unresectable stage III non-squamous non-small cell lung cancer: NJLCG1001.

BACKGROUND: The optimal regimen for concurrent chemoradiotherapy (CCRT) of locally advanced non-squamous non-small cell lung cancer (NSCLC) was not definitive. We conducted randomized phase II study, NJLCG0601, and chemoradiotherapy with uracil/tegafur (UFT) and cisplatin achieved promising efficacy without severe toxicities. Here, we evaluated between this regimen and pemetrexed plus cisplatin in chemoradiotherapy for stage III non-squamous NSCLC. METHODS: Patients with inoperable stage III non-squamous NSCLC were randomly assigned in a 1:1 ratio to UFT 400 mg/m2 on days 1-14 and 29-42, and cisplatin 80 mg/m2 on days 8 and 36 (UP), or cisplatin 75 mg/m2 and pemetrexed 500 mg/m2 on days 1, 22, and 43 (PP). Involved-field radiotherapy (IFRT) underwent from day 1 to a total dose of 66 Gy in 33 fractions. Consolidation chemotherapy after CCRT was prohibited for this study. The primary endpoint was defined as 2-year overall survival (OS). This trial was registered in the University Hospital Medical Information Network Clinical Trials Registry (UMIN000003948). RESULTS: From November 2010 to June 2017, 86 patients were entered from 11 institutions. Median follow-up was 54 months. Of the 85 eligible patients, the 2-year OS rate was 78.6% (95% CI, 62.8-88.3%) in UP and 85.5% (95% CI, 70.5-93.2%) in PP. Median PFS and OS was 12.3 and 64.2 months in UP, 26.2 months and not reached in PP, respectively. Grade 3/4 febrile neutropenia was more frequent in the UP group (14.0% vs. 2.0%). CONCLUSIONS: Both UP and PP with IFRT achieved the expected 2-year OS. PP engendered more favorable OS and PFS compared to UP in terms.

Differences in patterns of recurrence of squamous cell carcinoma and adenocarcinoma after radiotherapy for stage III non-small cell lung cancer.

PURPOSE: To evaluate the differences in patterns of recurrence and treatment results by histology after definitive radiotherapy for stage III non-small cell lung cancer (NSCLC) in Japan. MATERIALS AND METHODS: Patients with stage III NSCLC who underwent definitive radiotherapy between 2000 and 2016 in our institution were included. A total of 217 patients were enrolled. Propensity score matching was used to exclude the following confounding factors: (1) age (≥70 years or <70 years), (2) gender, (3) T factor, (4) N factor, (5) Eastern Cooperative Oncology Group performance status score and (6) smoking status (Brinkman index ≥400 or <400). RESULTS: The median observation period for survivors was 55.1 months. After propensity score matching, the Sqcc and adenocarcinoma groups each included 62 paired patients. There was no significant difference in OS or PFS between the adenocarcinoma and Sqcc groups. However, rates of recurrence in the GTV-primary site (p = 0.009) and GTV-lymph node site (p = 0.037) were significantly higher in patients with Sqcc than in patients with adenocarcinoma. New metastatic recurrence was more frequent in patients with adenocarcinoma than in patients with Sqcc (p = 0.025). CONCLUSION: There were significant differences in patterns of recurrence after definitive (chemo)radiotherapy between patients with Sqcc and patients with adenocarcinoma.

Hyperfractionated radiotherapy for re-irradiation of recurrent esophageal cancer.

PURPOSE: Re-irradiation is a treatment option for recurrent esophageal cancer patients with a history of radiotherapy, but there is a risk of severe late adverse effects. This study focused on the efficacy and safety of re-irradiation using hyperfractionated radiotherapy. MATERIALS AND METHODS: Twenty-six patients who underwent re-irradiation by the hyperfraction technique using twice-daily irradiation of 1.2 Gy per fraction for recurrent esophageal cancer were retrospectively included in this study. The overall survival period after the start of secondary radiotherapy and the occurrence of late adverse effects were investigated. RESULTS: Of 26 patients, 21 (81%) received re-irradiation with definitive intention and 21 (81%) underwent concurrent chemotherapy. The median re-irradiation dose was 60 Gy in 50 fractions in 25 treatment days, and the median accumulated irradiation dose in equivalent dose in 2 Gy per fraction was 85.4 Gy with an α/ß value of 3. The median interval between two courses of radiotherapy was 21.0 months. The median overall survival period was 15.8 months and the 1-year and 3-year overall survival rates were 64.3% and 28.3%, respectively. Higher dose of re-irradiation and concurrent chemotherapy significantly improved survival (p < 0.001 and p = 0.019, respectively). Severe late adverse effects with the Common Terminology Criteria for Adverse Events grade 3 or higher were observed in 5 (19.2%) patients, and 2 (7.7%) of them developed a grade 5 late adverse effect. CONCLUSION: High-dose re-irradiation using a hyperfractionated schedule with concurrent chemotherapy might be related to good prognosis, while the rate of late severe adverse effects is not high compared with the rates in past reports.

Effect of radiotherapy after breast-conserving surgery in elderly patients with early breast cancer according to the AJCC 8th Edition Breast Cancer Staging System in Japan.

BACKGROUND: The number of elderly patients in Japan with breast cancer has been gradually increasing. The aim of this study was to determine the efficacy of radiotherapy (RT) after breast-conserving surgery (BCS) for elderly patients with early breast cancer who were restaged according to the 8th Edition Breast Cancer Staging System. METHODS: We reviewed patients age ≥ 65 years who received BCS and adjuvant RT or BCS alone for breast cancer between 2010 and 2015 in our institution and restaged those patients using the AJCC 8th edition pathological prognostic staging system. We compared relapse-free survival (RFS) and overall survival (OS) rates in the RT group and no RT group. RESULTS: A total of 170 patients were eligible for analysis: 94 (55.3%) were treated with RT and 76 (44.7%) were treated without RT. Age (p < 0.01) was associated with the use of RT. Adjuvant RT significantly improved RFS (95.75% vs 84.21%, p = 0.02). There was no significant difference between the OS rates in the two groups. Univariate analysis showed that pathologic T stage and N stage were significantly associated with both RFS and OS and that histologic grade, chemotherapy, HER2, and RT were significantly associated with RFS, but not with OS. RT reduced the risk of recurrence (HR = 0.56, 95% CI = 0.19-0.96, p = 0.04). CONCLUSIONS: RT was associated with significantly improved RFS, but had no significant impact on OS in elderly patients with breast cancer after BCS. Adjuvant RT should be performed even for elderly patients with early breast cancer.

Dose-Dependent Radiation-Induced Myocardial Damage in Esophageal Cancer Treated With Chemoradiotherapy: A Prospective Cardiac Magnetic Resonance Imaging Study.

PURPOSE: The purpose of this prospective study was to evaluate radiation-induced myocardial damage after mediastinal radiation therapy (RT) using late gadolinium-enhancement (LGE) magnetic resonance imaging (MRI). METHODS AND MATERIALS: We enrolled 19 patients with esophageal cancer who were expected to have long-term survival by definitive treatment. They underwent delayed contrast-enhanced MRI (19 patients before treatment, 19 patients 6 months after treatment, and 12 patients 1.5 years after treatment). Dose distribution of the left ventricle was made using computed tomography, and the dose volume histogram of the left ventricle was calculated. Myocardial signal intensities in individual MRIs were normalized by the mean values in regions receiving low doses (<5 Gy). Changes in the normalized signal intensities after mediastinal radiation therapy were compared among regions where irradiation doses were 0 to 10 Gy, 10 to 20 Gy, 20 to 30 Gy, 30 to 40 Gy, 40 to 50 Gy, and 50 to 60 Gy, and we investigated whether intensity change was detected in a dose-dependent manner. RESULTS: The registered patients were treated with concurrent chemoradiotherapy with a median total dose of 60 Gy (50.4-66 Gy). Chemotherapy consisting of cisplatin and 5-fluorouracil was administered. In the population-based dose-response curve, dose-dependent intensity changes progressively increased in regions receiving more than 30 Gy. The averages of relative intensity change at 6 months and 1.5 years after treatment were 1.1% and -1.9% at 20 to 30 Gy and 37.5% and 17.5% at 40 to 50 Gy, respectively. LGE in regions receiving more than 30 Gy was detected in 68% (13/19) of the patients. CONCLUSIONS: A dose-dependent relationship for myocardial signal intensity change was found by using LGE MRI. It may be necessary to reduce the volume of the myocardium receiving more than 30 Gy.

A long-term survival case following salvage stereotactic radiotherapy for local recurrence after definitive chemoradiotherapy for stage III non-small cell lung cancer.

A 56-year-old male with stage IIIA (UICC 7th) non-small cell lung cancer (adenocarcinoma) received radiotherapy with 66 Gy/33 fractions concomitant with CBDCA and PTX. A partial response was achieved after chemoradiotherapy and the tumor continued to shrink over a period of 1 year; however, regrowth of the tumor attached to the aortic arch was observed without any other residual tumor or metastases. We diagnosed recurrence with slightly increased 18F-FDG uptake (maximum standardized uptake value: 12.2). Stereotactic radiotherapy was performed for the relapsed lesion with 60 Gy/10 fractions. The patient has survived for more than 5 years after stereotactic radiotherapy without recurrence or metastases, although he has been suffering from chest pain that has required treatment with a low dose of oxycodone.

Non-invasive quantitative measures of qualitative grading effectiveness as the indices of acute radiation dermatitis in breast cancer patients.

BACKGROUND: Recent improvement of machinery evaluation for the skin changes in various therapies enabled us to evaluate fine changes quantitatively. In this study, we performed evaluation of the changes in radiation dermatitis (RD) using quantitative and qualitative methods, and verified the validity of the conventional qualitative assessment for clinical use. METHODS: Forty-three breast cancer patients received conventional fractionated radiotherapy to whole breast after breast-conserving surgery. Erythema, pigmentation and skin dryness were evaluated qualitatively, and biophysical parameters of RD were measured using a Multi-Display Device MDD4 with a Corneometer for capacitance, a Tewameter for transepidermal water loss (TEWL), a Mexameter for erythema index and melanin index. Measurements were performed periodically until 1 year. RESULTS: The quantitative manifestations developed serially from skin erythema followed by dryness and pigmentation. Quantitative measurements detected the effects of irradiation earlier than that of qualitative indices. However, the grades of the domains in RD by qualitative and quantitative assessment showed similar time courses and peak periods. However, no significant correlation was observed between the skin dryness grade and skin barrier function. In contrast to serial increase in pigmentation grades, melanin index showed initial decrease followed by marked increase with significant correlation with pigmentation grades. CONCLUSION: Subjectively and objectively measured results of RD were almost similar course and peak points through the study. Therefore, validity of the conventional qualitative scoring for RD is confirmed by the present quantitative assessments. Instrumental evaluations revealed the presence of modest inflammatory changes before radiotherapy and long-lasting skin dryness, suggesting indication of intervention for RD.

Prognostic value of the AJCC 8th edition staging system for Japanese patients treated with surgery followed by radiotherapy for breast cancer.

BACKGROUND: American Joint Committee on Cancer (AJCC) 8th Edition Breast Cancer Staging System, biological information in addition to anatomical information was added as a basis for prognosis evaluation, but its prognostic impact in Japanese patients treated with postoperative radiotherapy has not been discussed. To determine the applicability of the updated prognostic staging system, we evaluated the prognostic value and confirmed the effectiveness of this system in patients in whom postoperative radiotherapy was performed. MATERIALS AND METHODS: Patients who were treated with postoperative radiotherapy for breast cancer in our institution between January 2011 and December 2015 were restaged by the AJCC 8th pathological prognosis staging system, and then overall survival (OS), disease-free survival (DFS) rates and hazard ratios (HR) were analyzed to compare the predictive fit of the two staging systems. RESULTS: Five hundred and seven patients who in whom postoperative radiotherapy was performed for breast cancer were enrolled in this study. 36.1% patients were downstaged and 5.3% patients were upstaged from the 7th to 8th editions staging system classification. Kaplan-Meier curves and HRs showed differences in OS and DFS rates between the 7th edition and 8th edition staging systems. The AJCC 8th edition prognostic stage system has a better prognostic prediction of OS and DFS than does the 7th edition anatomic stage system. CONCLUSIONS: Compared with the 7th edition in breast cancer, AJCC 8th edition prognostic stage system has more precise stratification and superior prognostic value, providing a more accurate reference for the choice of radiotherapy for patients with breast cancer.

Clinical experience of pelvic radiotherapy or chemoradiotherapy for postoperative uterine cervical cancer using intensity-modulated radiation therapy.

The purpose of this study was to reveal treatment outcomes and toxicity after pelvic intensity-modulated radiotherapy (IMRT) for postoperative uterine cervical cancer of Japanese patients. Consecutive patients who were treated with pelvic IMRT for postoperative cervical cancer in our institute were retrospectively analyzed. Relapse-free survival (RFS) and overall survival (OS) were calculated using the Kaplan-Meier estimator, and log-rank tests were used to compare differences. From the database, 62 patients were identified. The pathology was squamous cell carcinoma in 44 patients and other pathology in 18 patients. Of the 62 patients, 35 had high-risk prognostic factors and 27 patients had intermediate-risk prognostic factors. The prescribed radiation doses were 50 Gy in 25 fractions for 58 patients and 50.4 Gy in 28 fractions for 4 patients. One patient received a vaginal cuff boost. Chemotherapy was administered in 36 patients. During the median follow-up period of 50.9 months, there was no locoregional failure. Six patients in the high-risk group relapsed, but none of the patients in the intermediate-risk group relapsed (P = 0.02). The 3-year OS and RFS rates were 98.2% and 90.9%, respectively. Significant factors related to RFS were squamous cell carcinoma pathology (P = 0.02), pathological T stage (P = 0.04), surgical margin status (P < 0.01) and multiple lymph nodes metastases (P < 0.01). Grade 3 or more toxicity occurred in 6 patients. Four patients had obstruction of the intestine, and 2 patients had stenosis of the urinary tract. In clinical practice, the use of pelvic IMRT for postoperative cervical cancer of Japanese patients showed a low rate of toxicity without decreasing the efficacy.

A case report and review of the literature: cardiotoxicities after radiotherapy for breast cancer patients with high-risk factors of cardiovascular disease.

Cardiovascular disease (CVD) is an important adverse effect of radiotherapy and is responsible for increased morbidity and mortality in long-term survivors with breast cancer. Patients may have pre-existing cardiovascular risk factors before treatment of breast cancer, and the effects of pre-existing cardiovascular risk factors can be compounded by radiotherapy. We report a case of left breast cancer in a 63-year-old female with a high risk of CVD who was suspected of having radiation-induced myocardium injury 1 year after postoperative adjuvant therapy. Radiation oncologists should not only reduce the adverse effects by perfecting radiotherapy technology but also consider reducing other high-risk factors for CVD.

FDG-PET might not contribute to improving survival in patients with locally advanced inoperable esophageal cancer.

BACKGROUND: In Japan, positron emission tomography using 18F-fluorodeoxyglucose (FDG-PET) has been covered by the national health insurance for esophageal cancer since 2006. FDG-PET is commonly performed in advanced esophageal cancer. The aim of this study was to determine the effect of FDG-PET on survival in patients with locally advanced inoperable esophageal cancer. METHODS: We retrospectively reviewed all patients with cT4 and without M1 esophageal cancer on CT in our institution between 2000 and 2014, and data for 78 patients who meet the eligibility criteria described below were used for analysis in this study. The eligibility criteria included (1) cT4 esophageal cancer without distant metastases or M1 lymph node metastasis (UICC 2002), (2) histologically proven squamous cell carcinoma, (3) 20-79 years of age, (4) having undergone at least 1 cycle of concomitant chemotherapy, (5) having been irradiated with 50 Gy or more, and (6) no other active malignant tumor during treatment. RESULTS: Two patients were excluded because abdominal lymph node metastases or neck lymph node metastases were detected by FDG-PET. In 78 eligible patients, FDG-PET was not performed before treatment in 41 of the 78 patients and was performed in the other patients. The median observation period was 68 months. The 3-year and 5-year overall survival rates in 78 patients were 36.9% and 30.8%, respectively. There was no significant difference in overall survival or progression-free survival between patients in whom FDG-PET was performed and those in whom FDG-PET was not performed (12.0 months vs. 11.0 months, p = 0.920 and 6.0 months vs. 6.0 months, p = 0.844, respectively). CONCLUSIONS: Compared with only CT, additional information from FDG-PET is not associated with improving survival in patients with locally advanced esophageal cancer. Our results suggest that FDG-PET might not have much meaning for survival in locally advanced esophageal cancer.

Hypofractionated Radiotherapy for Anaplastic Thyroid Carcinoma: 15 Years of Experience in a Single Institution.

BACKGROUND: Anaplastic thyroid carcinoma (ATC) is a rare cancer and has a poor prognosis. Several radiation protocols have been reported, but the results were not satisfactory. OBJECTIVE: The aim of this study was to determine the effect of hypofractionated radiotherapy. METHODS: Thirty-three patients who received radiotherapy for ATC between January 2000 and December 2014 were retrospectively included. We defined hypofractionated radiotherapy as a single dose ≥5 Gy. RESULTS: Nineteen patients were treated with hypofractionated radiotherapy. Twenty-eight patients died, and 27 of those patients died from ATC. Sixteen patients died from distant metastasis and 6 from local recurrence. In the hypofractionated radiotherapy group, local recurrence occurred in 5 patients and 1 of them died from active bleeding from a local tumor. There was local recurrence in 7 patients who received the other protocol, and 5 of them died from asphyxiation, active bleeding, or uncontrollable growth of a local tumor on the neck. The median overall survival (OS) was 5 months. In multivariate analysis, patients who received an equivalent dose in 2-Gy fractions (EQD2) ≥50 Gy had significantly better OS (p = 0.016). In univariate analysis, patients who received hypofractionated radiotherapy did not have significantly better OS (p = 0.872) or local control (p = 0.090). The χ2 test showed that significantly fewer patients died from local recurrence in the hypofractionated radiotherapy group (p = 0.025). CONCLUSIONS: Multivariate analysis showed that an EQD2 ≥50 Gy resulted in better OS, and hypofractionated radiotherapy decreased the rate of mortality from local recurrence.

[Field Shape Optimization Technique Based on Dose Volume Histogram Using Daily Cone-beam Computed Tomography in Three-dimensional Conformal Radiation Therapy for Localized Prostate Cancer: Develop and Evaluation].

This study aimed to develop and evaluate field shape optimization technique based on dose calculation using daily cone-beam computed tomography (CBCT) to compensate for interfractional anatomic changes in three-dimensional conformal radiation therapy (3D-CRT) for prostate cancer. For each of 10 patients, 9-10 CBCT images were obtained throughout the treatment course. The prostate, seminal vesicles, and rectum were manually contoured in all CBCT images. Subsequently, plan adaptation was performed with a program developed in-house. This program calculates dose distributions on CBCT images and optimizes field shape to minimize rectal dose while keeping the target at the optimal dose coverage (the planning target volume D95% receives 95% of the prescription dose). To evaluate the adaptive planning approach, we re-calculated dose distributions on CBCT images based on the conventional and adaptive plans. For the entire cohort, plan adaptation improved rectal V50 Gy, V60 Gy, V65 Gy, and V70 Gy by -7.71±8.43%, -8.30±8.90%, -7.91±8.51% and -7.03±7.70% on average (±SD), respectively. Our results demonstrate that adaptive planning approach is superior to the conventional planning approach for optimizing dose distribution, and this adaptive approach can optimize field shape in 3 min. The proposed approach can be an effective solution for the problem of interfractional anatomic changes in 3D-CRT for prostate cancer.

Assessment and agreement of the CT appearance pattern and its severity grading of radiation-induced lung injury after stereotactic body radiotherapy for lung cancer.

PURPOSE: Radiographic severity of radiation-induced lung injury (RILI) has not been well-studied. The goal of this study was to assess the CT appearance pattern and severity of RILI without consideration of the clinical presentation. MATERIAL AND METHODS: A total of 49 patients, 41 with primary lung cancer and 8 with metastatic lung cancer, were treated by 4-fraction stereotactic body radiotherapy (SBRT). RILI after SBRT was separately assessed by two observers. The early and late CT appearance patterns and CT-based severity grading were explored. RESULTS: The median follow-up period was 39.0 months. In the early CT findings of observers 1 and 2, there was diffuse consolidation in 15 and 8, diffuse ground glass opacity (GGO) in 0 and 0, patchy consolidation and GGO in 17 and 20, patchy GGO in 3 and 3, and no changes in 10 and 14, respectively (kappa = 0.61). In late CT findings of observer 1 and 2, there were modified conventional pattern in 28 and 24, mass-like pattern in 8 and 11, scar-like pattern in 12 and 12, and no changes in 1 and 2, respectively (kappa = 0.63). In the results of the CT-based grading by observers 1 and 2, there were grade 0 in 1 and 2, grade 1 in 10 and 14, grade 2 in 31 and 29, grade 3 in 7 and 4, and none of grade 4 or more, respectively (kappa = 0.66). According to multivariate analyses (MVA), the significant predicting factors of grade 2 or more CT-based RILI were age (p = 0.01), oxygen dependence (p = 0.03) and interstitial shadow (p = 0.03). CONCLUSIONS: The agreement of the CT appearance and CT-based grading between two observers was good. These indicators may be able to provide us with more objective information and a better understanding of RILI.