T. Yanagi

Treatment and prognosis of patients with late rectal bleeding after intensity-modulated radiation therapy for prostate cancer.

BackgroundRadiation proctitis after intensity-modulated radiation therapy (IMRT) differs from that seen after pelvic irradiation in that this adverse event is a result of high-dose radiation to a very small area in the rectum. We evaluated the results of treatment for hemorrhagic proctitis after IMRT for prostate cancer.MethodsBetween November 2004 and February 2010, 403 patients with prostate cancer were treated with IMRT at 2 institutions. Among these patients, 64 patients who developed late rectal bleeding were evaluated. Forty patients had received IMRT using a linear accelerator and 24 by tomotherapy. Their median age was 72 years. Each patient was assessed clinically and/or endoscopically. Depending on the severity, steroid suppositories or enemas were administered up to twice daily and Argon plasma coagulation (APC) was performed up to 3 times. Response to treatment was evaluated using the Rectal Bleeding Score (RBS), which is the sum of Frequency Score (graded from 1 to 3 by frequency of bleeding) and Amount Score (graded from 1 to 3 by amount of bleeding). Stoppage of bleeding over 3 months was scored as RBS 1.ResultsThe median follow-up period for treatment of rectal bleeding was 35 months (range, 12–69 months). Grade of bleeding was 1 in 31 patients, 2 in 26, and 3 in 7. Nineteen of 45 patients (42%) observed without treatment showed improvement and bleeding stopped in 17 (38%), although mean RBS did not change significantly. Eighteen of 29 patients (62%) treated with steroid suppositories or enemas showed improvement (mean RBS, from 4.1 ± 1.0 to 3.0 ± 1.8, p = 0.003) and bleeding stopped in 9 (31%). One patient treated with steroid enema 0.5-2 times a day for 12 months developed septic shock and died of multiple organ failure. All 12 patients treated with APC showed improvement (mean RBS, 4.7 ± 1.2 to 2.3 ± 1.4, p < 0.001) and bleeding stopped in 5 (42%).ConclusionsAfter adequate periods of observation, steroid suppositories/enemas are expected to be effective. However, short duration of administration with appropriate dosage should be appropriate. Even when patients have no response to pharmacotherapy, APC is effective.

Correlation between the serum KL-6 level and the grade of radiation pneumonitis after stereotactic body radiotherapy for stage I lung cancer or small lung metastasis.

0167-8140/

Helical and Static-port Tomotherapy Using the Newly-developed Dynamic Jaws Technology for Lung Cancer.

see front matter 2011 Elsevier Irelan doi:10.1016/j.radonc.2011.05.031 ⇑ Corresponding author. Address: Department of Ra sity Graduate School of Medical Sciences, 1 Kawasu Nagoya 467-8601, Japan. E-mail address: h-iwa-ncu@nifty.com (H. Iwata). Serum levels of a sialylated carbohydrate antigen KL-6, a marker for interstitial pneumonitis, were serially measured before and after stereotactic body radiotherapy (SBRT) for lung tumors. It was suggested that KL-6 levels before and after SBRT would help to predict the occurrence of P Grade 2 radiation pneumonitis. 2011 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 101 (2011) 267–270

Toxicity and efficacy of three dose-fractionation regimens of intensity-modulated radiation therapy for localized prostate cancer

With the newly developed dynamic jaws technology, radiation dose for the cranio-caudal edges of a target can be lowered in the treatment with tomotherapy. We compared dynamic-jaw- and fixed-jaw-mode plans for lung cancer. In 35 patients, four plans using the 2.5-cm dynamic-, 2.5-cm fixed-, 5.0-cm dynamic-, and 5.0-cm fixed-jaw modes were generated. For 10 patients with upper lobe stage I lung cancer, the helical tomotherapy mode was used. Fifty-six Gy in 8 fractions was prescribed as a minimum coverage dose for 95% of the target (D95%). For 25 patients with locally advanced lung cancer, plans using four static ports (TomoDirect® mode) were made. Sixty Gy in 30 daily fractions for the primary tumor and swollen lymph nodes and 51 Gy in 30 fractions for prophylactic lymph node areas were prescribed as median doses. The mean conformity index of the planning target volume were similar among the four plans. The mean V5 Gy of the lung for 2.5-cm dynamic-, 2.5-cm fixed-, 5.0-cm dynamic-, and 5.0-cm fixed-jaw mode plans were 18.5%, 21.8%, 20.1%, and 29.4%, respectively (p < 0.0001), for patients with stage I lung cancer, and 37.3%, 38.7%, 40.4%, and 44.0%, respectively (p < 0.0001), for patients with locally advanced lung cancer. The mean V5 Gy of the whole body was 1,826, 2,143, 1,983, and 2,939 ml, respectively (p < 0.0001), for patients with stage I lung cancer and 4,849, 5,197, 5,220, and 6,154 ml, respectively (p < 0.0001), for patients with locally advanced lung cancer. Treatment time was reduced by 21-39% in 5.0-cm dynamic-jaw plans compared to 2.5-cm plans. Regarding dose distribution, 2.5-cm dynamic-jaw plans were the best, and 5.0-cm dynamic-jaw plans were comparable to 2.5-cm fixed-jaw plans with shorter treatment times. The dynamic-jaw mode should be used instead of the conventional fixed-jaw mode in tomotherapy for lung cancer.

Radiotherapy for hilar or mediastinal lymph node metastases after definitive treatment with stereotactic body radiotherapy or surgery for stage I non-small cell lung cancer

Outcomes of three protocols of intensity-modulated radiation therapy (IMRT) for localized prostate cancer were evaluated. A total of 259 patients treated with 5-field IMRT between 2005 and 2011 were analyzed. First, 74 patients were treated with a daily fraction of 2.0 Gy to a total of 74 Gy (low risk) or 78 Gy (intermediate or high risk). Then, 101 patients were treated with a 2.1-Gy daily fraction to 73.5 or 77.7 Gy. More recently, 84 patients were treated with a 2.2-Gy fraction to 72.6 or 74.8 Gy. The median patient age was 70 years (range, 54–82) and the follow-up period for living patients was 47 months (range, 18–97). Androgen deprivation therapy was given according to patient risk. The overall and biochemical failure-free survival rates were, respectively, 96 and 82% at 6 years in the 2.0-Gy group, 99 and 96% at 4 years in the 2.1-Gy group, and 99 and 96% at 2 years in the 2.2-Gy group. The biochemical failure-free rate for high-risk patients in all groups was 89% at 4 years. Incidences of Grade ≥2 acute genitourinary toxicities were 9.5% in the 2.0-Gy group, 18% in the 2.1-Gy group, and 15% in the 2.2-Gy group (P = 0.29). Cumulative incidences of Grade ≥2 late gastrointestinal toxicity were 13% in the 2.0-Gy group at 6 years, 12% in the 2.1-Gy group at 4 years, and 3.7% in the 2.2-Gy group at 2 years (P = 0.23). So far, this stepwise shortening of treatment periods seems to be successful.

Efficacy of stereotactic radiotherapy for brain metastases using dynamic jaws technology in the helical tomotherapy system

PURPOSE Management of regional lymph node (LN) recurrence is an important issue in definitive treatment of non-small cell lung cancer (NSCLC). We evaluated clinical outcomes of conventional radiotherapy for hilar or mediastinal LN metastases developing after stereotactic body radiotherapy (SBRT) or surgery for stage I NSCLC. METHODS AND MATERIALS Between 2004 and 2008, 26 patients with hilar or mediastinal LN metastases without local recurrence and distant metastasis after SBRT (n = 14) or surgery (n = 12) were treated with conventional radiotherapy. Twelve of the 14 post-SBRT patients (86%) were judged medically inoperable at the time of SBRT. All patients were treated to the hilum and mediastinum with conventional daily fractions of 2.0 Gy (n = 25) or 2.4 Gy (n = 1). The median total dose for treating metastatic LN was 60 Gy (range, 54-66 Gy) for the post-SBRT patients and 65 Gy (range, 60-66 Gy) for the post-surgery patients. Only 1 of the 14 post-SBRT patients and 8 of the 12 post-surgery patients received chemotherapy. RESULTS For all 26 patients, the overall and cause-specific survival rates at 3 years from radiation for LN metastases were 36% and 51%, respectively (14% and 39%, respectively, for the 14 post-SBRT patients and both 64% for the 12 post-surgery patients). Three of the SBRT patients were alive at 35 to 43 months with (n = 2) or without (n = 1) further recurrence, and 4 of the post-surgery patients were alive at 36 to 62 months with (n = 2) or without (n = 2) further recurrence. The incidence of ≥grade 2 pulmonary toxicity was 49% at 1 year (53% for post-SBRT patients and 44% for post-surgery patients). A grade 5 pulmonary toxicity was observed in 1 of the post-SBRT patients. CONCLUSIONS Conventional radiotherapy could successfully salvage LN relapses after SBRT as well as after surgery in 7 of 26 patients. Radiotherapy in this setting appears reasonably well tolerated.

Definitive Radiotherapy Following Induction Chemotherapy for Hypopharyngeal Cancer: Selecting Candidates for Organ-Preserving Treatment Based on the Response to Induction Chemotherapy

Objective: Dynamic jaws (DJ) are expected to be useful in stereotactic radiotherapy (SRT) for brain metastases (BM). The efficacy and optimal dose fractionation were investigated. Methods: In a planning study, 63 treatment plans were generated for the following 3 conditions: 1.0-cm fixed jaws (FJ), 2.5-cm FJ and 2.5-cm DJ. In a clinical study, 30 Gy/3 fr, 35 Gy/5 fr or 37.5 Gy/5 fr were prescribed depending on tumour size. Clinical results of groups treated with 2.5-cm DJ plans and 1.0-cm FJ were compared. Results: In the planning study, the treatment times in 2.5-cm DJ and FJ plans were less than that in 1.0-cm FJ plans (p < 0.001). The brain doses in 1.0-cm FJ plans and 2.5-cm DJ plans were smaller than those in 2.5-cm FJ plans (p < 0.05). In the clinical study, 34 patients with 68 BM were treated with SRT. Of those, 15 patients with 34 BM were treated with 2.5-cm DJ plans and 19 patients with 34 BM were treated with 1.0-cm FJ plans. The overall survival and local tumour control (LC) rates were 52 and 93% at 12 months, respectively. The DJ system achieved favourable LC and 29% shorter treatment time compared with the FJ system (p < 0.001). Grade 2 or 3 necrosis occurred more frequently in patients with 15 cc or larger tumour volumes (p = 0.05). Conclusion: DJ technology enables treatment time to be reduced without worsening the dose distribution and clinical efficacy. The prescribed doses in this study may be acceptable for patients with small tumour volumes. Advances in knowledge: DJ technology enables treatment time to be reduced without worsening the dose.

Chemo-selection with docetaxel, cisplatin and 5-fluorouracil (TPF) regimen followed by radiation therapy or surgery for pharyngeal and laryngeal carcinoma

The outcomes of induction chemotherapy followed by radiotherapy for hypopharyngeal carcinoma were analyzed to determine whether response to induction chemotherapy could be a useful parameter for selecting candidates for organ-preserving therapy.Forty-three patients with hypopharyngeal carcinoma were treated with definitive radiotherapy with or without concurrent chemotherapy following induction chemotherapy. The predominant induction chemotherapy regimens involved cisplatin and 5-fluorouracil with or without docetaxel. The patients that responded to the induction chemotherapy received definitive organ-preserving treatment. Patients who did not respond to induction chemotherapy were considered for surgery, but only those patients who underwent definitive radiotherapy were analyzed in this study. Conventional radiotherapy was administered in all patients. The associations between clinical parameters including age, sex, performance status (PS), tumor site, T-category, N-category, stage, the regimen of induction chemotherapy, the response to induction chemotherapy, the presence/absence of concurrent chemotherapy, overall survival (OS), and local control (LC) were analyzed.Among the surviving patients, the follow-up period ranged from 10-145 months (median: 46 months). The 3-year OS and LC rates for all 43 patients were 61% and 70%, respectively. The 3-year OS and LC rates of the responders were 73% and 81%, respectively, whereas those of the non-responders were 29% and 40%, respectively. In multivariate analysis, only PS was correlated with overall survival (p=0.03). The complication rates were acceptable in all groups.Responders to induction chemotherapy appear to be good candidates for definitive organ-preserving treatment. Chemoselection appears to aid treatment selection in patients with hypopharyngeal carcinoma.

Dose–volume histogram comparison between static 5-field IMRT with 18-MV X-rays and helical tomotherapy with 6-MV X-rays

Background Induction chemotherapy for patients with head and neck cancer is widely performed, and several advantages of induction chemotherapy have been reported. However, there is currently insufficient evidence to strongly recommend induction chemotherapy. In this study, we analyzed the outcomes for patients treated with induction chemotherapy and subsequent definitive treatments. Methods Operable patients with untreated oropharyngeal, hypopharyngeal and laryngeal squamous cell carcinoma treated with induction chemotherapy were included in this retrospective study. We conducted induction chemotherapy using docetaxel, cisplatin and 5-fluorouracil and performed subsequent surgical treatment or radiotherapy according to the response to induction chemotherapy. Results A total of 65 patients were included in this study, and 50 patients (76.9%) had Stage IV tumors. The response to induction chemotherapy was CR in two patients, PR in 55 patients, and SD in eight patients. The subsequent definitive treatment was radiotherapy in 60 patients, and surgery in five patients. The 3-year overall survival rates for patients who received radiotherapy and surgery were 88.4% and 75.0%, respectively (P = 0.30). The 3-year disease-free survival rates for patients who received radiotherapy and surgery were 68.0% and 0%, respectively (P = 0.01). The 3-year laryngeal dysfunction free survival rates for patients who received RT and surgery were 77.8% and 0%, respectively (P < 0.01). Conclusions We achieved favorable survival outcomes and high larynx preservation rates. Our results suggest that induction chemotherapy using TPF regimen is one of the optimal treatment strategies when treating head and neck cancers. Further prospective studies with a larger cohort are required to confirm our findings.

Definitive Concurrent Chemotherapy and High Dose (60-70Gy) Radiation Therapy for Esophageal Cancer

Abstract We treated prostate cancer patients with static 5-field intensity-modulated radiation therapy (IMRT) using linac 18-MV X-rays or tomotherapy with 6-MV X-rays. As X-ray energies differ, we hypothesized that 18-MV photon IMRT may be better for large patients and tomotherapy may be more suitable for small patients. Thus, we compared dose–volume parameters for the planning target volume (PTV) and organs at risk (OARs) in 59 patients with T1–3 N0M0 prostate cancer who had been treated using 5-field IMRT. For these same patients, tomotherapy plans were also prepared for comparison. In addition, plans of 18 patients who were actually treated with tomotherapy were analyzed. The evaluated parameters were homogeneity indicies and a conformity index for the PTVs, and D2 (dose received by 2% of the PTV in Gy), D98, Dmean and V10–70 Gy (%) for OARs. To evaluate differences by body size, patients with a known body mass index were grouped by that index ( <21; 21–25; and >25 kg/m2). For the PTV, all parameters were higher in the tomotherapy plans compared with the 5-field IMRT plans. For the rectum, V10 Gy and V60 Gy were higher, whereas V20 Gy and V30 Gy were lower in the tomotherapy plans. For the bladder, all parameters were higher in the tomotherapy plans. However, both plans were considered clinically acceptable. Similar trends were observed in 18 patients treated with tomotherapy. Obvious trends were not observed for body size. Tomotherapy provides equivalent dose distributions for PTVs and OARs compared with 18-MV 5-field IMRT. Tomotherapy could be used as a substitute for high-energy photon IMRT for prostate cancer regardless of body size.