Retrospective comparison between definitive stereotactic body radiotherapy and radical surgery for 538 patients with early-stage non-small cell lung cancer in a single institution.

Introduction: Survival information for stereotactic body radiotherapy (SBRT) and surgery for stage I non-small cell lung cancer (NSCLC) was examined. Methods: Stage I NSCLC patients who underwent surgery or SBRT between 2012 and 2016 were retrospectively enrolled in this single-institution study. Using the Kaplan--Meier method and Cox regression model, overall survival (OS) was estimated and compared. Results: Among 538 enrolled patients, compared to the surgery group (443), the SBRT group (95) had more complications (P = 0.01), worse performance status (P = 0.001), and were older (P < 0.001). Three-year OS was 70.5% post SBRT and 90.1% postsurgery. The 3-year cancer-specific survival (CSS) and disease-free survival (DFS) post SBRT and postsurgery were 92.7% vs. 92.3% and 61.1% vs 79.3%, respectively. Three-year locoregional and distant control rates post SBRT and postsurgery were 85.6% vs. 90.1% and 82.5% vs. 86.4%, respectively. Multivariate analysis using the Cox model, including age, T-stage, CCI, and C/T ratio and treatment, showed the surgery group's OS to be significantly superior to that of the SBRT group (HR of SBRT per surgery: 1.90, 95%CI: 1.12-3.21, P = 0.017). No significant differences were observed in rates of adverse events. Conclusion: Although OS was better in the surgery group, no differences in CSS existed. This analysis suggests the need for future studies that compare specific radical surgeries and SBRT in a prospective and randomized setting.

A retrospective analysis of radiotherapy in the treatment of external auditory canal carcinoma.

External auditory canal carcinoma (EACC) is a rare disease. The current study aimed to evaluate the clinical outcomes of patients treated with external beam radiotherapy (EBRT) for EACC. The present study retrospectively reviewed 34 consecutive patients treated for EACC with EBRT between February 2001 and January 2019 at the University of Tokyo Hospital. Clinical staging was performed according to the modified Pittsburgh classification. Of all the included patients, seven patients were in the early stages (I or II) and 27 in the advanced stages (III or IV) of EACC. A total of 16 patients underwent EBRT and surgery (S+RT) pre- and/or postoperatively, while 18 patients underwent definitive radiotherapy (dRT). The median prescribed doses for the S+RT and dRT groups were 66 and 70 Gy, respectively. The median follow-up period for all patients was 22.4 months (range, 2-205 months). The 5-year overall survival rates of the S+RT and dRT groups were 66.7 and 45.1%, respectively. The progression-free survival rate at 5-year was 55.6% (95% confidence interval: 36.5-71.1%) for the entire cohort. A total of 14 patients experienced disease relapse after treatment, consisting of 11 locoregional recurrences and three distant metastases. The current study revealed the clinical outcomes of EBRT for EACC.

Survival comparison between radical surgery and definitive chemoradiation in 267 esophageal squamous cell carcinomas in a single institution: A propensity-matched study.

OBJECTIVE: To compare radical surgery with definitive chemoradiation (CRT) for esophageal squamous cell carcinoma using propensity score (PS) matching at our single institution. MATERIALS AND METHODS: A total of 386 consecutive, surgically treated and 243 CRT-treated cases between 2001 and 2014 were analyzed. PS was calculated using multivariable analysis (logistic regression) for pairs of variables such as treatment time, age, sex, primary tumor location, clinical stage, and clinical T- and N-stage for patients after excluding clinical T4 and M1 cases. According to PS, 133 surgically-treated and 134 CRT-treated cases were selected randomly by software. RESULTS: The patients' median age was 68 years in the CRT group and 71 years in the surgery group. Clinical stage II-III, T3, N0 (according to the 7th American Joint Committee on Cancer-2009), and upper plus middle thoracic esophageal disease were seen in 68%, 44%, 54%, and 59%, respectively, in the CRT group and 64%, 47%, 55%, and 64%, respectively, in the surgery group. The 3- and 5-year overall survival was 47.1% and 34.0% in the CRT group and 68.3% and 54.4% in the surgery group (p = 0.0019). The 3- and 5-year progression-free survival was 45.3% and 38.8% in the CRT group and 61.1% and 54.4% in the surgery group (p = 0.022). CONCLUSION: CRT may be inferior to surgery in survival, although a selection bias for patients selected for a non-operative approach cannot be excluded, especially since surgery is the standard of care at this institution. A prospective randomized clinical trial will be necessary to draw a definite conclusion.

Prognostic factors in patients after definitive chemoradiation using involved-field radiotherapy for esophageal cancer in a phase II study.

BACKGROUND: A prospective study was performed on the use of chemoradiotherapy (CRT) for esophageal cancer (EC) with involved-field radiation therapy (IFRT), based on 18-fluorodeoxyglucose positron-emission tomography. Prognostic factors for overall survival (OS) were analyzed. METHODS: Eligible patients included 63 adults with newly diagnosed, untreated, inoperable stage I-IV EC with lymph node metastases. Patients received 80 mg/m2 nedaplatin per day on day 1, 800 mg/m2 5-fluorouracil on days 1-4 intravenously repeated every 28 days for two to four cycles, and combined IFRT. Irradiation was applied only to the primary tumor and positive lymph nodes. RESULTS: Three-year progression-free survival and OS rates were 44.9% and 47.5%, respectively. The median survival time was 31.5 months. In univariate analyses for OS, Karnofsy Performance Scale <90% (P = 0.027), initial stage (P = 0.0087), T stage (P = 0.066), N stage (P = 0.000086), M stage of M1 (P = 0.0042), dysphagia score (P = 0.00017), tumor marker squamous cell carcinoma antigen >1.5 ng/mL (P = 0.0054), gross tumor volume (GTV) > 60 cc (P = 0.00011), and relative dose intensity (RDI) of chemotherapy ≤50% (P = 0.063) were found to be associated with significantly or marginally worse OS. In multivariate analyses for OS, GTV ≥ 60 cc (P = 0.00040), RDI < 50% (P = 0.00034), and cN2-3 (P = 0.0020) were associated with significantly worse OS. CONCLUSION: GTV, RDI and N grading, were associated with OS after definitive CRT using IFRT for EC.

Efficacy and feasibility of ambulatory treatment-based monthly nedaplatin plus S-1 in definitive or salvage concurrent chemoradiotherapy for early, advanced, and relapsed esophageal cancer.

BACKGROUND: Standard chemoradiotherapy (CRT) using cisplatin (CDDP) and 5-fluorouracil (5-FU) is an optional treatment for patients with stage II-III esophageal cancer. However, there are some demerits in this regimen because CDDP administration requires a large transfusion volume and 5-FU must be continuously infused over 24 h. Therefore, hospitalization is unavoidable. We collected retrospectively the data of definitive CRT with nedaplatin and S-1 as carried out in our institution. METHODS: Patients with early and advanced esophageal cancer and relapsed esophageal cancer after radical surgery were included. Nedaplatin 80 mg/m(2) was given on days 1 and 29, and S-1 80 mg/m(2) on days 1-14 and 29-42. No prophylactic treatment with granulocyte colony stimulating factor was administered. Patients received two courses of concurrent radiotherapy of more than 50 Gy with or without two additional courses as adjuvant therapy every 4 weeks. RESULTS: Between August 2011 and June 2015, 89 patients (age range, 44-86 years; K-PS 90-100, 81 %; squamous cell carcinoma histology, 97 %; definitive/salvage CRT, 75/25 %) were collected. Twenty-one (24 %) patients completed four cycles, and 94 % received two or more cycles. Grade 4 leukopenia, thrombocytopenia, and anemia occurred in 12, 7, and 10 % of the patients, respectively. Five patients developed febrile neutropenia. Grade 3 non-hematological toxicity included infection in 12 %, mucositis/esophagitis in 3 %, kidney in 3 %, and fatigue in 3 %. Sixty-four patients (72 %) received the prescribed full dose and full cycles of chemotherapy. A complete response was achieved in 76 patients (85 %). The 3-year overall survival rate was 54.4 % in definitive CRT and 39.8 % in salvage CRT, respectively. Sixty-two subjects (70 %) received treatment as outpatients. CONCLUSIONS: Nedaplatin and S-1 in combination with radiotherapy is feasible, and toxicity is tolerable. This treatment method has the potential to shorten hospitalization without impairing the efficacy of CRT.

Involved-field radiotherapy (IFRT) versus elective nodal irradiation (ENI) in combination with concurrent chemotherapy for 239 esophageal cancers: a single institutional retrospective study.

BACKGROUND: This retrospective study on early and locally advanced esophageal cancer was conducted to evaluate locoregional failure and its impact on survival by comparing involved field radiotherapy (IFRT) with elective nodal irradiation (ENI) in combination with concurrent chemotherapy. METHODS: We assessed all patients with esophageal cancer of stages I-IV treated with definitive radiotherapy from June 2000 to March 2014. Between 2000 and 2011, ENI was used for all cases excluding high age cases. After Feb 2011, a prospective study about IFRT was started, and therefore IFRT was used since then for all cases. Concurrent chemotherapy regimen was nedaplatin (80 mg/m(2) at D1 and D29) and 5-fluorouracil (800 mg/m(2) at D1-4 and D29-32). RESULTS: Of the 239 consecutive patients assessed (120 ENI vs. 119 IFRT), 59 patients (24.7%) had stage IV disease and all patients received at least one cycle of chemotherapy. The median follow-up time for survivors was 34.0 months. There were differences in 3-year local control (44.8% vs. 55.5%, p = 0.039), distant control (53.8% vs. 69.9%, p = 0.021) and overall survival (34.8% vs. 51.6%, p = 0.087) rates between ENI vs. IFRT, respectively. Patients treated with IFRT (8 %) demonstrated a significantly lower risk (p = 0.047) of high grade late toxicities than with ENI (16%). IFRT did not increase the risk of initially uninvolved or isolated nodal failures (27.5% in ENI and 13.4% in IFRT). CONCLUSIONS: Nodal failure rates in clinically uninvolved nodal stations were not increased with IFRT when compared to ENI. IFRT also resulted in significantly decreased esophageal toxicity, suggesting that IFRT may allow for integration of concurrent systemic chemotherapy in a greater proportion of patients. Both tendencies of improved loco-regional progression-free survival and a significant increased overall survival rate favored the IFRT arm over the ENI arm in this study.

Repeated episodes of spontaneous regression/progression of cervical adenocarcinoma after adjuvant chemoradiation therapy: a case report.

INTRODUCTION: Spontaneous regression of cancer is thought to be a rare event. Here, we report an extremely rare case of repeated episodes of spontaneous regression and progression of recurrent cervical adenocarcinoma. CASE PRESENTATION: We report here a case of a 56-year-old Japanese woman who was diagnosed with cervical adenocarcinoma. Her hilar and mediastinal lymph nodes were swollen 6 years after the initial diagnosis and subsequent treatment, and were found to be pathologically malignant by mediastinal biopsy. Then, without any treatment, the hilar and mediastinal lymph nodes spontaneously regressed with decreases in tumor size and serum tumor marker levels, as confirmed by a decrease in uptake of fluorodeoxyglucose during positron emission tomography-computed tomography. Subsequently, although there were repeated episodes of increase and decrease in her serum tumor marker levels and lymph node size, her activities of daily living were and are well preserved. CONCLUSIONS: While spontaneous regression of a malignant tumor is a rare event, our case is even rarer in that repeated episodes of spontaneous regression/progression of cervical adenocarcinoma occurred.

Analysis of motion of the rectum during preoperative intensity modulated radiation therapy for rectal cancer using cone-beam computed tomography.

PURPOSE: The purpose of the present study was to quantify the inter-fractional motion of the rectum and the rectal and bladder volumes using CBCT scans taken during chemoradiation therapy (CRT) for rectal cancer. Also, assessment was made for a better margin for simultaneous integrated boost - intensity modulated radiation therapy (SIB-IMRT) for rectal cancer. METHODS AND MATERIALS: There were 32 patients in this study undergoing preoperative CRT for rectal cancer. Each rectum and bladder was contoured on all planning CTs and CBCTs (day 1, 7, 13, 19, 25). The target volume was configured by adding margins (0, 3, 5, 7, 10, and 15 mm) to the rectum on planning CT. The respective percentage of rectal volume that exceeds the target volume was calculated for each of these margins. The percentage of bladder volume that exceeds the bladder volume in the planning CT and motion of the center of gravity of rectum were also analyzed. RESULTS: Planning CTs and series of each 5 CBCTs for 32 patients were analyzed in this study. The rectal volume tended to shrink week after week. The mean values (± SD) in the 32 series per patient of the percentage of rectum on the CBCTs exceeding target volume in which the margins of 0, 3, 5, 7, 10, and 15 mm were added to the rectum on planning CT were 20.7 ± 12.5%, 7.2 ± 8.3%, 3.9 ± 5.9%, 2.1 ± 3.9%, 0.7 ± 1.8%, and 0.1 ± 0.3%, respectively. No association was seen between the percentage of changes of bladder volume and motion of rectal centroid. CONCLUSIONS: In this study, we estimated the motion of the rectum using planning CT and CBCT. Ten to fifteen mm is a sufficient margin for the rectum during SIB-IMRT for rectal cancer in the supine position.

Involved-field irradiation concurrently combined with nedaplatin/5-fluorouracil for inoperable esophageal cancer on basis of (18)FDG-PET scans: a phase II study.

PURPOSE: A prospective study was performed on chemoradiotherapy (CRT) for esophageal cancer using involved-field radiation therapy (IFRT) based on 18-fluorodeoxyglucose positron-emission tomography. The goal of this phase II study was to evaluate the efficacy of the IFRT procedure in newly diagnosed esophageal cancer. PATIENTS AND METHODS: Eligible patients were adults with newly diagnosed untreated, inoperable esophageal cancer in stages I-IV with lymph node metastases. Patients received nedaplatin 80mg/m(2) per day on day 1, 5-fluorouracil 800mg/m(2) on days 1-4 intravenously repeated every 28days for 2-4 cycles, and combined IFRT. Elective nodal irradiation was not performed. Irradiation was applied only to the primary tumor and positive lymph nodes. RESULTS: From September 2009 to July 2012, of the 63 patients enrolled, 58 were evaluable for response. The primary end point of isolated out-of-field loco-regional nodal recurrence was seen in only two patients. The expectant rate was assumed to be less than 5%. The threshold value was set as 10% to calculate the number of registrations. Progression-free and overall survival rates at 36months were 47.7% and 51.1%, respectively. The median progression-free survival was 34.6months, and overall survival was 38.4months. Salvage surgery was tried for 11 patients (17.5%) due to residual or recurrent disease. CONCLUSION: The primary end point of the trial was demonstrated, indicating the efficacy of IFRT in the treatment of inoperable esophageal cancer mostly of squamous cell carcinoma.

Volumetric modulated arc therapy for lung stereotactic radiation therapy can achieve high local control rates.

PURPOSE: The aim of this study was to report the outcome of primary or metastatic lung cancer patients undergoing volumetric modulated arc therapy for stereotactic body radiation therapy (VMAT-SBRT). METHODS AND MATERIALS: From October 2010 to December 2013, consecutive 67 lung cancer patients received single-arc VMAT-SBRT using an Elekta-synergy system. All patients were treated with an abdominal compressor. The gross tumor volumes were contoured on 10 respiratory phases computed tomography (CT) datasets from 4-dimensional (4D) CT and merged into internal target volumes (ITVs). The planning target volume (PTV) margin was isotropically taken as 5 mm. Treatment was performed with a D95 prescription of 50 Gy (43 cases) or 55 Gy (12 cases) in 4 fractions for peripheral tumor or 56 Gy in 7 fractions (12 cases) for central tumor. RESULTS: Among the 67 patients, the median age was 73 years (range, 59-95 years). Of the patients, male was 72% and female 28%. The median Karnofsky performance status was 90-100% in 39 cases (58%) and 80-90% in 20 cases (30%). The median follow-up was 267 days (range, 40-1162 days). Tissue diagnosis was performed in 41 patients (61%). There were T1 primary lung tumor in 42 patients (T1a in 28 patients, T1b in 14 patients), T2 in 6 patients, three T3 in 3 patients, and metastatic lung tumor in 16 patients. The median mean lung dose was 6.87 Gy (range, 2.5-15 Gy). Six patients (9%) developed radiation pneumonitis required by steroid administration. Actuarial local control rate were 100% and 100% at 1 year, 92% and 75% at 2 years, and 92% and 75% at 3 years in primary and metastatic lung cancer, respectively (p =0.59). Overall survival rate was 83% and 84% at 1 year, 76% and 53% at 2 years, and 46% and 20% at 3 years in primary and metastatic lung cancer, respectively (p =0.12). CONCLUSIONS: Use of VMAT-based delivery of SBRT in primary in metastatic lung tumors demonstrates high local control rates and low risk of normal tissue complications.

Individually wide range of renal motion evaluated by four-dimensional computed tomography.

OBJECTIVES: Assessment of physiologic renal motion in order to optimize abdominal intensity-modulated radiation therapy and stereotactic body radiation therapy. METHODS AND MATERIALS: Twenty patients with a median age of 47 years underwent computed tomography simulation and four-dimensional computed tomography acquisition. Thirty-nine kidneys were contoured during ten phases of respiration to estimate renal motion. RESULTS: Kidney motion was not related to age (p = 0.42), sex (p = 0.28), height (p = 0.75), or body weight (p = 0.63). The average +/- standard deviation (SD) of movement of the center of gravity for all subjects was 11.1 +/- 4.8 mm in the cranio-caudal (CC) direction (range, 2.5-20.5 mm), 3.6 +/- 2.1 mm in the anterior-posterior (AP) direction (range, 0.6-8.0 mm), and 1.7 +/- 1.4 mm in the right-left (RL) direction (range, 0.4-5.9 mm). Renal motion strongly correlated with the respiratory phases (r > 0.97 and p < 0.01 in all three directions). CONCLUSIONS: Renal motion was independent of age, sex, height, or body weight. Renal motion in all directions was strongly respiration dependent, but motion in the cranio-caudal direction showed wide individual variation. In a clinical setting, it will be necessary to evaluate renal respiratory motion separately in each individual.