Factors associated with compensatory lung growth after pulmonary lobectomy for lung malignancy: an analysis of lung weight and lung volume changes based on computed tomography findings.

PURPOSE: To establish the factors associated with compensatory lung growth (CLG) in human adults. METHODS: The subjects of this study were 216 patients who underwent pulmonary lobectomy between January 2008 and March 2015 and had computed tomography (CT) scans done before and 2 years after surgery with no signs of recurrence. The predicted postoperative values of lung volume and lung weight, based on the preoperative CT data, were compared with those 2 years after surgery. RESULTS: When the predicted postoperative values were considered to be 100%, the mean lung volume and lung weight 2 years after surgery were 116 ± 16% and 115 ± 19%, respectively. CLG was defined as both lung volume ≥ 110% and lung weight ≥ 106% (CLG group; n = 108). Both univariate and multivariate analyses showed that younger age (≤ 60 years), a larger number of resected subsegments (≥ 10), and a light- (< 20 pack-years) or non-smoking history were significantly associated with CLG. CONCLUSIONS: This study identified younger age, a light- or non-smoking history, and a large resection volume as the predictors of CLG in patients who underwent pulmonary lobectomy for lung malignancy. All of these three factors may be reasonably connected to CLG.

Definitive Local Therapy for Oligo-recurrence in Patients With Completely Resected Non-small Cell Lung Cancer.

BACKGROUND: The aim of this study was to elucidate a curable subgroup among patients with non-small cell lung cancer (NSCLC) who developed postoperative recurrence. PATIENTS AND METHODS: Between 1986 and 2012, among the 1408 patients who underwent complete anatomic lung resection for NSCLC at our institution, 420 developed recurrence. After excluding 14 patients with insufficient information about recurrence, 406 were included in this retrospective study. We investigated the association between several clinicopathologic factors and postrecurrence overall survival (PR-OS) and postrecurrence progression-free survival (PR-PFS). RESULTS: The 5-year PR-OS and PR-PFS rates were 14.0% and 5.9%, respectively. By multivariate analysis, female sex, longer disease-free interval, specific targeted therapy, recent recurrence, oligo-recurrence, and definitive local therapy (DLT) were found to be independent favorable prognostic factors for both PR-OS and PR-PFS. Among these 6 prognostic factors, although female sex, longer disease-free interval, and specific targeted therapy were associated with a prolonged median PR-PFS time, they were not associated with an improved 5-year PR-PFS rate. In contrast, recent recurrence, oligo-recurrence, and DLT were associated with improvement in both the median PR-PFS time and 5-year PR-PFS rate. CONCLUSIONS: We found that recent recurrence, oligo-recurrence, and DLT were associated with an improved median PR-PFS time and long-term PR-PFS rate in patients with postoperative recurrence after complete resection of NSCLC. On the basis of these results, we believe that DLT should be considered first for patients with oligo-recurrence before applying noncurative treatment.

High-dose-rate intracavitary brachytherapy for recurrent cervical cancer in the vaginal stump after hysterectomy.

This study aimed to evaluate the treatment outcomes of patients who received high-dose-rate intracavitary brachytherapy (HDR-BT) using Iridium-192 with or without external beam radiotherapy as definitive treatment for recurrent cervical cancer after hysterectomy. Thirty-six patients with local recurrence after hysterectomy received radiotherapy including HDR-BT from 2005 to 2013. Overall survival, local control rate, and progression-free survival were estimated retrospectively via the Kaplan-Meier method. Late adverse events were also scored using the Common Terminology Criteria for Adverse Events (version 3.0). Median follow-up time was 38 (range, 7.4-101.3) months. The 3-year estimates of overall survival, local control rate, and progression-free survival were 100.0%, 82.8%, and 76.8%, respectively. Two patients (5.6%) had grade 2 lymphedema, but no other adverse events greater than grade 2 were reported. In conclusion, HDR-BT was an effective treatment modality for patients with cervical cancer recurrence in the vaginal stump.

Study Protocol: Prospective Study of Concurrent Chemoradiotherapy with S-1 and Hypofractionated Radiotherapy for Outpatients with Early Glottic Squamous Cell Carcinomas

Background: The recommended treatment strategies for early glottic carcinoma with intent of larynx preservation are primarily radiotherapy. However, the outcomes of radiotherapy for bulky T1 or T2 glottic carcinoma are unsatisfactory. We designed a protocol consisting of concurrent chemoradiotherapy using S-1 as the radiosensitizer. We have performed this protocol in patients with favorable T2 lesions and demonstrated its efficacy and safety. In contrast, we have treated non-bulky T1 glottic carcinomas with 2.25 Gy per fraction, for a total of 25-28 fractions, starting in 2011 to improve efficacy and shorten the treatment period. Since this treatment strategy was implemented for T1 disease, no local failure has occurred to date, and it appears to be almost as safe as radiotherapy using 2.0 Gy per fraction. With the aim of improving the local control rate and shortening the treatment period primarily for favorable T2 disease, we changed the dose of radiation in our protocol from 2.0 Gy to 2.25 Gy per fraction, for a total of 25 fractions (from 30 fractions). The present study aims to evaluate the efficacy and safety of this new protocol. Methods: This study will be conducted as a clinical, prospective, single-armed, non-randomized trial. Patients are to receive S-1 (55.3 mg /m2 /day, once daily) and radiotherapy (2.25 Gy per fraction, for a total of 25 fractions). S-1 and radiotherapy are started on the same day that radiotherapy is performed, 3-6 hours after oral administration of S-1. The primary study aim is the 3-year local control rate. The secondary study aims are overall survival, voice-preservation survival, disease-free survival, complete response rate, completion rate, and toxicity. Result and conclusion: This is the first single-center, non-randomized, prospective study of concurrent chemoradiotherapy with S-1 and hypofractionated radiotherapy to be conducted. The trial will evaluate the efficacy and safety of our protocol.

Clinical outcomes of 125I brachytherapy with and without external-beam radiation therapy for localized prostate cancer: results from 300 patients at a single institution in Japan.

The aim of this study was to determine the outcomes and adverse events for 300 men with prostate cancer treated with 125iodine (125I) brachytherapy with and without external-beam radiation therapy (EBRT) at a single institution in Japan. Between February 2005 and November 2011, 300 consecutive patients with clinically localized prostate cancer were treated with 125I brachytherapy at the Nagoya University Hospital. A total of 271 men were treated with implants with doses of 145 Gy, and 29 men were treated with implants with doses of 110 Gy combined with EBRT (40-50 Gy/20-25 fractions). The median patient age was 69 years (range, 53-83 years). The median follow-up period was 53 months (range, 5-99 months). According to the National Comprehensive Cancer Network risk classification, 132 men (44%) had low-risk, 147 men (29%) had intermediate-risk and 21 men (7%) had high-risk disease. The 5-year overall survival rate, biochemical relapse-free survival rate, and disease-specific survival rates were 93.5%, 97.3% and 98.5%, respectively. Two men (0.6%) died of prostate cancer and 10 men (3.3%) died of other causes. Seventeen men (5.6%) experienced Grade 2 rectal bleeding in all: 12 (41.4%) of 29 in brachytherapy with EBRT, and 5 (1.8%) of 271 in brachytherapy alone. The rates of Grade 2 and 3 genitourinary toxicity were 1.0% and 1.7%, respectively. Excellent local control was achieved at our hospital for localized prostate cancer with 125I brachytherapy with and without EBRT. Gastrointestinal and genitourinary toxicities were acceptable.

Optimized treatment strategy of radiotherapy for early glottic squamous cell carcinomas: An initial analysis.

The purpose of this study was to evaluate the clinical outcomes of radiotherapy for patients with T1/T2 glottic carcinoma. Patients with T1/T2 glottic carcinoma histopathologically diagnosed with squamous cell carcinoma and treated at our hospital between 2007 and 2015 were analyzed retrospectively. Our strategy for T1/T2 glottic carcinoma was as follows: radiotherapy alone with 2.25 Gy per fraction to a total of 25-28 fractions for patients with non-bulky T1 glottic carcinoma; concurrent chemoradiotherapy with oral S-1 and radiotherapy with 2 Gy per fraction to a total of 30 fractions for patients with T1 bulky/T2 favorable glottic carcinoma; or chemoradiotherapy with high-dose cisplatin and radiotherapy with 2 Gy per fraction to a total of 35 fractions for T2 unfavorable glottic carcinoma. Forty-eight patients were eligible. The median follow-up period among surviving patients was 38 months (range, 11-107). The disease was T1a in 23%, T1b in 13%, and T2 in 65% of patients. The 3-year local control rate in all patients, T1a, T1b, and T2 was 96.7%, 100%, 100%, and 96.0%, respectively. Of the 46 patients, one with T2 glottic carcinoma developed recurrent disease at the primary site, and one with T2 glottic carcinoma had lymph node recurrences in the neck. Acute Grade 3 dermatitis occurred in 8 (17%) patients and late Grade 2 hypothyroidism occurred in 2 (4%) patients. This retrospective study shows that our optimized treatment strategy of radiotherapy depending on the stage of early glottic carcinoma is not only effective but also well-tolerated.

Postoperative chemoradiation therapy using high dose cisplatin and fluorouracil for high- and intermediate-risk uterine cervical cancer.

The purpose of this retrospective study was to analyze data in patients with stage IB-IIB uterine cervical cancer who were treated with concurrent chemoradiotherapy (CCRT) with high dose cisplatin and fluorouracil as postoperative adjuvant therapy. Between February 2003 and November 2011, 76 patients with FIGO stage IB-IIB cervical cancer were analyzed. Seventy patients were treated with postoperative CCRT and 6 patients were treated with radiation therapy alone. Data related to overall survival (OS), disease-free survival (DFS), toxicity, and failure pattern were analyzed. The median patient age was 45 years (range, 20-80 years). The median follow-up duration was 63 months (range, 10-125 months). Fifty-eight patients (76.3%) had a squamous cell histologic type, 55 patients (72.4%) had lymphovascular invasion, 31 patients (40.8%) had parametrial invasion, and 28 patients (36.8%) had lymph node metastases. Five-year OS and DFS were 96% and 92%, respectively. Five-year DFS in stage IB1 patients was significantly higher than in stage IB2-IIB patients (p = 0.022). Nineteen patients (25%) had grade 3 or 4 neutropenia, 13 patients (17.1%) had grade 3 anemia, and 2 patients (2.6%) had grade 3 thrombocytopenia, but none of these patients died from the disease. Three patients experienced chronic toxicity: one had bladder perforation, one had hydronephrosis, and one experienced ileus. CCRT as postoperative adjuvant therapy resulted in good survival and outcome without severe toxicity.

Late Rectal Toxicity from Image-guided Intensity Modulated Radiotherapy for Prostate Cancer.

AIM: Late rectal toxicity (LRT) was retrospectively evaluated in men with prostate cancer treated with image-guided intensity modulated radiotherapy (IG-IMRT). PATIENTS AND METHODS: Between May 2008 and December 2009, 47 men with prostate adenocarcinoma were treated with IG-IMRT using in-room computed tomography (CT). RESULTS: The median time to grade 2 LRT was 12 months (range=1-24 months). Two of 3 men who developed grade 2 LRT had received treatment for diabetes, and the other was receiving anticoagulant/antiplatelet therapy (AC therapy). Their rectal wall V70 (the volume of rectal wall receiving 70 Gy) values were 12.6%, 13.0%, and 13.3%. Univariate analysis revealed that V70 of the rectal wall was the only significant risk factor for LRT (p=0.0073). CONCLUSION: No man with V70 ≤12.0% experienced grade 2 LRT. Strict rectal wall V70 ≤12% dose constraints should be considered when treating prostate cancer patients who are also receiving diabetic or AC therapy.

A Randomized, Double-Blind Pilot Trial of Hydrolyzed Rice Bran versus Placebo for Radioprotective Effect on Acute Gastroenteritis Secondary to Chemoradiotherapy in Patients with Cervical Cancer.

We aimed to evaluate the radioprotective effect of hydrolyzed rice bran (HRB) on acute gastroenteritis due to chemoradiotherapy for treatment of cervical cancer. This placebo-controlled, double-blind study was conducted as an exploratory investigation of the colitis-inhibiting effects of HRB in alleviating acute-phase gastrointestinal side effects of chemoradiotherapy. The study involved 20 patients (10 in the HRB group, 10 in the control group). The patients in the control group underwent the same chemoradiotherapy regimen as those in the HRB group, but they received a placebo instead of HRB. The diarrheal side effect assessment score was lower in the HRB than control group, and a trend toward a reduction in diarrhea symptoms was observed with the oral intake of HRB. Additionally, no significant difference was observed in the administration of intestinal regulators and antidiarrheal agents, but again the assessment score was lower in the HRB than control group, and diarrhea symptoms were alleviated with the oral intake of HRB. A trend toward no need for strong antidiarrheal agents was seen. Although this study was an exploratory clinical trial, the results suggest that HRB may relieve diarrhea, an acute-phase gastrointestinal side effect of chemoradiotherapy.

A phase I/II trial of intraoperative breast radiotherapy in an Asian population: 5-year results of local control and cosmetic outcome.

BACKGROUND: To date, there are no reports of intraoperative radiotherapy (IORT) use with long-term follow up as a method of accelerated partial breast irradiation (APBI) in Asian countries. We initiated a prospective phase I/II clinical trial of IORT in Japan in 2007, and herein, we report the 5-year follow-up results. MATERIALS AND METHODS: The following inclusion criteria were used for enrollment in the trial: (1) tumor size < 2.5 cm, (2) desire for breast-conserving surgery, (3) age >50 years, and (4) negative margins after resection. In February 2009, the eligibility criteria were changed to include only patients with sentinel lymph node-negative disease. In phase I, the radiotherapy dose was escalated from 19 Gy/fr to 21 Gy/fr, incremented by 1 Gy per step, with 3 patients in each step. Doses were escalated after all patients in the preceding cohort had completed treatment and exhibited only grade 1 or 2 toxicities at a given dose level. The recommended phase II dose was set at 21 Gy at 90 % isodose. The primary endpoint was early toxicity. Secondary endpoints were long-term efficacy and late toxicity. In addition, Hypertrophic scarring was evaluated retrospectively as a cosmetic outcome by a radiation oncologist. RESULTS: Between December 2007 and March 2010, 32 women with breast cancer were enrolled in the trial. The median age was 65 years (51-80 years), and the median follow-up time was 6 years. No recurrence or metastasis was observed in any patient. Grade 2 fibrosis was detected in 3 patients as an acute adverse event and in 2 patients as a late adverse event. Ten patients developed a hypertrophic scar 1 year after the IORT; the number of patients decreased to 7 in the 3 years of follow-up. CONCLUSION: The first group of female Asian patients tolerated the treatment with IORT in this Phase I/II study and remained recurrence-free for more than 5 years after treatment. However, 24 % of the patients developed hypertrophic scarring, an event that is being further examined in our ongoing multi-center Phase II trial of IORT for early breast cancer.

Critical evaluation of a prospective study of concurrent chemoradiotherapy with S-1 for early glottic carcinoma.

AIM: To improve the outcomes of radiotherapy alone for T2 glottic carcinoma (GC), we initiated a prospective study of concurrent chemoradiotherapy with S-1 for patients with early GC, primarily T2 cases. We report the efficacy and safety of this protocol. PATIENTS AND METHODS: Eligible patients had T1b or T2 glottic squamous cell carcinomas. Patients received S-1 (55.3 mg/m(2)/day, once daily) and radiotherapy (2 Gy/day, five days/week, to a total of 30 fractions). RESULTS: Thirteen patients were eligible. Complete responses were observed in all 13 patients (100%). At a median follow-up duration of 53 months (range=23-68 months), the 3-year local control and overall survival rates were both 100%. Grade 3 dermatitis occurred in only one patient. CONCLUSION: This chemoradiotherapy protocol is well -tolerated and effective in patients with early glottic carcinoma. Furthermore, due to its once-daily administration, this protocol is considered to be easier than usual chemoradiotherapy, and makes outpatient-treatment possible.

Comparison of three measurements on computed tomography for the prediction of less invasiveness in patients with clinical stage I non-small cell lung cancer.

BACKGROUND: A greater proportion of ground-glass opacity (GGO) is well known to be strongly associated with less invasive lung adenocarcinoma. Recently, the solid area diameter has also been reported to be a simple and better marker for the same purpose compared with the whole nodule diameter. METHODS: From 1997 to 2009, 383 patients with clinical T1-2N0M0 non-small cell lung cancer (NSCLC) with a solid area of 3 cm or less underwent surgical resection, and their preoperative high-resolution computed tomographic images were preserved in Digital Imaging and Communications in Medicine format. Less invasive lung cancer was defined as having no vascular, lymphatic, or pleural invasion or lymph node metastasis. We compared the solid area and whole nodule diameters and proportion of GGO, with the objective of predicting less invasive lung cancer. RESULTS: Among the 383 patients, 187 were men, 335 had adenocarcinoma histologic type, 242 had less invasive lung cancer, and 43 experienced recurrence. Receiver operating characteristic (ROC) analysis to predict less invasive lung cancer showed that the area under the curve of proportion of GGO was the highest (0.848; 95% confidence interval [CI], 0.810-0.886), followed by the solid area diameter (0.785; 95% CI, 0.740-0.829), and then whole nodule diameter (0.621; 95% CI, 0.565-0.677). Multiple logistic regression analyses revealed that proportion of GGO was the only significant predictor of less invasive lung cancer. The proportion of GGO was also found to be a significant prognostic factor of disease-free survival (DFS) along with solid area diameter by multivariate analysis. Regardless of the solid area diameter, no patient with a greater proportion of GGO (> 50%) experienced recurrence. CONCLUSIONS: Proportion of GGO remains important for predicting less invasive lung cancer.

Characteristics of subsolid pulmonary nodules showing growth during follow-up with CT scanning.

OBJECTIVE: The positive results of a screening CT scan trial are likely to lead to an increase in the use of CT scanning, and, consequently, an increase in the detection of subsolid nodules. Noninvasive methods including follow-up with CT scanning, to determine which nodules require invasive diagnosis and surgical treatment, should be defined promptly. METHODS: Between 2000 and 2008, from our database of . 60,000 examinations with CT scanning, we identified 174 subsolid nodules, which showed a ground-glass opacity area . 20% of the nodule and measured 2 cm in diameter, in 171 patients. We investigated the clinical characteristics and CT images of the subsolid nodules in relation to changes identified during the follow-up period. RESULTS: The nodule sizes ranged from 4 mm to 20 mm at the fi rst presentation. Nonsolid nodules numbered 98. During the follow-up period, 18 nodules showed resolution or shrinkage, and 41 showed growth of 2 mm or more in diameter. The time to 2-mm nodule-growth curves calculated by Kaplan-Meier methods indicated that the 2-year and 5-year cumulative percentages of growing nodules were 13% and 23% in patients with nonsolid nodules and 38% and 55% in patients with part-solid nodules, respectively. Multivariate analysis disclosed that a large nodule size ( . 10 mm) and history of lung cancer were significant predictive factors of growth in nonsolid nodules. CONCLUSIONS: An effective schedule for follow-up with CT scanning for subsolid nodules should be developed according to the type of subsolid nodule, initial nodule size, and history of lung cancer.

Alternating chemoradiotherapy in patients with nasopharyngeal cancer: prognostic factors and proposal for individualization of therapy.

The purpose of this study is to assess the efficacy of alternating chemoradiation in patients with nasopharyngeal cancer. From 1990-2006, 100 patients with nasopharyngeal cancer were treated with alternating chemoradiation at the Aichi Cancer Center. Of these, 4, 2, 23, 34, 13 and 23 patients were staged as I, IIA, IIB, III, IVA and IVB, respectively. The median radiation doses for primary tumors and metastatic lymph nodes were 66.6 Gy (range, 50.4-80.2 Gy) and 66 Gy (range, 40.4-82.2 Gy), respectively. A total of 82 patients received chemotherapy with both cisplatin and 5-fluorouracil (5-FU), while 14 patients received nedaplatin (CDGP) and 5-FU. With a median follow-up of 65.9 months, the 5-year rates of overall survival (OAS) and progression-free survival (PFS) were 78.1% and 68.3%, respectively. On multivariate analysis (MVA), elderly age, N3, and WHO type I histology proved to be significantly unfavorable prognostic factors of OAS. As for PFS, there were T4, N3, and WHO type I histology in MVA. Acute toxicities of hematologic and mucositis/dermatitis ≥ Grade 3 were relatively high (32%); however, they were well-managed. Late toxicities of ≥ Grade 3 were three (3%) mandibular osteomyelitis and one (1%) lethal mucosal bleeding. Results for alternating chemoradiation for nasopharyngeal carcinoma are promising. In order to improve outcomes, usage of intensity-modulated radiation therapy and application of active anticancer agents are hopeful treatments, especially for groups with poor prognosis factors with WHO type I histopathology, T4 and/or N3 disease.