Long-term survival outcomes and quality of life of image-guided proton therapy for operable stage I non-small cell lung cancer: A phase 2 study.

BACKGROUND AND PURPOSE: This study evaluated long-term efficacy, safety, and changes in quality of life (QOL) of patients after image-guided proton therapy (IGPT) for operable stage I non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: This single-institutional prospective phase 2 study enrolled patients with operable histologically confirmed stage IA or IB NSCLC (7th edition of UICC). The prescribed dose was 66 Gy relative biological effectiveness equivalents (GyRBE) in 10 fractions for peripheral lesions, or 72.6 GyRBE in 22 fractions for central lesions. The primary endpoint was the 3-year overall survival (OS). The secondary endpoints included disease control, toxicity, and changes in QOL score. RESULTS: We enrolled 43 patients (median age: 68 years; range, 47-79 years) between July 2013 to January 2021, of whom 41 (95 %) had peripheral lesions and 27 (63 %) were stage IA. OS, local control, and progression-free survival rates were 95 % (95 % CI: 83-99), 95 % (82-99), and 86 % (72-94), respectively, at 3 years, and 83 % (66-92), 95 % (82-99), and 77 % (60-88), respectively, at 7 years. Four patients (9 %) developed grade 2, and one patient (2 %) developed grade 3 radiation pneumonitis. No other grade 3 or higher adverse events were observed. In the QOL analysis, global QOL remained favorable; however, approximately 40 % of patients reported dyspnea at 3 and 24 months. CONCLUSION: Our findings suggest that IGPT provides effective disease control and survival in operable stage I NSCLC, particularly for peripheral lesions. Moreover, toxicity associated with IGPT was minimal, and patients reported favorable QOL.

Dose Prescription to Isodose Lines in Static Multi-Beam Stereotactic Body Radiotherapy for Lung Tumors: Which Line Is Optimal?

This study investigated the appropriate dose prescription method in static multi-beam stereotactic body radiotherapy for lung tumors. Static multi-beam stereotactic body radiotherapy is a mainstream treatment in Japan. Based on the hypothesis that dose prescription to lower isodose lines may improve planning target volume dose coverage and decrease doses to organs at risk, we investigated changes in dose-volume histograms with prescription to various isodose lines for planning target volume in static multi-beam stereotactic body radiotherapy. In all treatment plans, 45 Gy in 4 fractions were prescribed to 95% of the planning target volume. By adjusting the leaf margins of each beam, various prescription isodose lines encompassing 95% volume of the planning target volume were generated. The prescription isodose lines investigated were 40, 50, 60, 70, 80 and 90% lines relative to the maximum dose of each planning target volume. The conformity index, homogeneity index, mean lung dose, and V5-V40 of the lung were evaluated. The dose was calculated by the adaptive convolve algorithm. The conformity index was lowest in the 70% or 80% isodose plan. The mean lung doses and V10-V40 of the lung decreased steeply from the 90% to the 70% isodose plan, and was lowest in the 60% and 70% isodose plans. These indices increased in the 40% and 50% isodose plans. The optimal stereotactic body radiotherapy plans appeared to be dose prescription to the 60% or 70% isodose line. Further investigation is warranted to clarify the advantage of using this method clinically.

Clinical Outcomes of Intraoperative Radiotherapy, Postoperative Radiotherapy, and Definitive Radiotherapy for Non-metastatic Pancreatic Cancer.

OBJECTIVE: The aim of this study is to evaluate the utility of adjuvant radiotherapy (intraoperative radiotherapy, IORT; postoperative radiotherapy, PORT), and definitive radiotherapy for non-metastatic pancreatic cancer. METHODS: Ninety-nine patients were analyzed. Thirty patients underwent IORT with surgery, 31 underwent PORT after surgery, and 38 underwent definitive radiotherapy. Tumor stage [Union for International Cancer Control (UICC) 2009] was as follows: Stage I, 7; IIA, 16; IIB, 31; III, 45. The doses for IORT, PORT, and definitive radio therapy were 20 to 30, 40 to 64.6, and 50.4 to 61.2 Gy, respectively. Associations between clinical parameters including age, gender, tumor site, stage, performance status, surgical margin, and use of chemotherapy and local control (LC) or overall survival (OS) were analyzed. RESULTS: Follow-up periods for all patients were 1.1-145 months (median, 11). OS rate in the IORT, PORT, and definitive radiotherapy groups was 22%, 16%, and 6%, respectively, at 2 years. The 5-year OS rate was 13%, 3.2%, and 0%, respectively. Local control rate at 2 years was 33%, 35%, and 0%, respectively. No Grade ≥ 3 tox icities were observed. Distant metastasis was less common in the IORT group. Stage and surgical margin were sig nificant factors for OS after IORT. Performance status and chemotherapy were significant factors for OS after PORT and definitive radiotherapy. CONCLUSIONS: The present study showed the safety of the three treatment modalities, but the outcomes were not satisfactory. More intensive strategies including radiotherapy should be investigated.

Daily irradiation versus irradiation at two- to three-day intervals in stereotactic radiotherapy for patients with 1-5 brain metastases: study protocol for a multicenter open-label randomized phase II trial.

BACKGROUND: Radiobiological daily changes within tumors are considered to be quite different between stereotactic radiotherapy (SRT) (e.g., 50 Gy in 4 fractions) and conventional radiotherapy (e.g., 60 Gy in 30 fractions). We aim to assess the optimal interval of irradiation in SRT and compare outcomes of daily irradiation with irradiation at two- to three-day intervals in SRT for patients with one to five brain metastases (BM). METHODS: This study is conducted as a multicenter open-label randomized phase II trial. Patients aged 20 or older with one to five BM, less than 3.0 cm diameter, and Karnofsky Performance Status ≥70 are eligible. A total of 70 eligible patients will be enrolled. After stratifying by the number of BMs (1, 2 vs. 3-5) and diameter of the largest tumor (< 2 cm vs. ≥ 2 cm), we randomly assigned patients (1:1) to receive daily irradiation (Arm 1), or irradiation at two- to three-day intervals (Arm 2). Both arms are performed with total dose of 27-30 Gy in 3 fractions. The primary endpoint is an intracranial local control rate, defined as intracranial local control at initially treated sites. We use a randomized phase II screening design with a two-sided α of 0∙20. The phase II trial is positive with p < 0.20. All analyses are intention to treat. This study is registered with the UMIN-clinical trials registry, number UMIN000048728. DISCUSSION: This study will provide an assessment of the impact of SRT interval on local control, survival, and toxicity for patients with 1-5 BM. The trial is ongoing and is recruiting now. TRIAL REGISTRATION: UMIN000048728. Date of registration: August 23, 2022. https://center6.umin.ac.jp/cgi-bin/ctr/ctr_view_reg.cgi?recptno=R000055515 .

Clinical outcomes of image-guided proton therapy for histologically confirmed stage I non-small cell lung cancer.

BACKGROUND: Two prospective phase II trials were designed to assess the efficacy and safety of image-guided proton therapy (IGPT) for either medically inoperable or operable stage I non-small cell lung cancer (NSCLC). The present study reports the interim results of these trials. METHODS: Fifty-five patients with histologically confirmed stage I NSCLC (IA in 33 patients and IB in 22 patients; inoperable in 21 patients and operable in 34 patients) who received IGPT between July 2013 and February 2017 were analyzed. The median patient age was 71 years (range: 48-88 years). IGPT with fiducial metallic marker matching was performed for suitable patients, and a respiratory gating method for motion management was used for all treatments. Peripherally located tumors were treated with 66 Gy relative biological effectiveness equivalents (Gy(RBE)) in 10 fractions (n = 49) and centrally located tumors were treated with 72.6 Gy(RBE) in 22 fractions (n = 6). Treatment associated toxicities were evaluated using Common Toxicity Criteria for Adverse Events (v.4.0). RESULTS: Median follow-up was 35 months (range: 12-54 months) for survivors. For all patients, the 3-year overall survival, progression-free survival, and local control rates were 87% (95% confidence interval: 73-94%), 74% (58-85%), and 96% (83-99%), respectively. Fiducial marker matching was used in 39 patients (71%). Grade 2 toxicities observed were radiation pneumonitis in 5 patients (9%), rib fracture in 2 (4%), and chest wall pain in 5 (9%). There were no grade 3 or higher acute or late toxicities. CONCLUSIONS: IGPT appears to be effective and well tolerated for all patients with stage I NSCLC. TRIAL REGISTRATION: Lung-001, 13-02-09 (9), registered 11 June 2013 and Lung-002, 13-02-10 (10), registered 11 June 2013.

Definitive radiotherapy for hilar and/or mediastinal lymph node metastases after stereotactic body radiotherapy or surgery for stage I non-small cell lung cancer: 5-year results.

PURPOSE: The optimal treatment for hilar or mediastinal lymph node (LN) recurrence developing after stereotactic body radiotherapy (SBRT) for stage I non-small cell lung cancer remains unclear. This study evaluated 5-year results of radiotherapy in such patients in comparison with those for postoperative LN metastases. MATERIALS AND METHODS: Between 2004 and 2013, 27 patients with hilar and/or mediastinal LN metastases without local recurrence and distant metastasis after SBRT (n = 14) or surgery (n = 13) were treated with definitive conventional radiotherapy. The median total dose for treating metastatic LN was 60 Gy for the post-SBRT group and 66 Gy for the post-surgery group. RESULTS: The median follow-up for the 5 surviving patients was 62 months. The overall survival, cause-specific survival, progression-free survival, and local control rates at 5 years after mediastinal irradiation were 14%, 45%, 21%, and 58%, respectively, for the 14 patients in the post-SBRT group. These rates were 36%, 45%, 39%, and 92%, respectively for the post-surgery group (p = 0.066, 0.64, 0.38, and 0.41, respectively). Four patients in the post-SBRT group survived 3 or more years (range 36-92 months) after mediastinal irradiation. CONCLUSIONS: A proportion of patients in both groups achieved long-term survival by conventional radiotherapy.

Stereotactic body radiotherapy for stage I non-small-cell lung cancer using higher doses for larger tumors: results of the second study.

BACKGROUND: Efficacy of stereotactic body radiotherapy (SBRT) in stage I non-small-cell lung cancer (NSCLC) has almost been established. In Japan, the protocol of 48 Gy in 4 fractions over 4 days has been most often employed, but higher doses may be necessary to control large tumors. Previously, we conducted a clinical study using SBRT for stage I NSCLC employing different doses depending on tumor diameter, which was closed in 2008. Thereafter, a new study employing higher doses has been conducted, which is reported here. The purpose of this study was to review the safety and effectiveness of the higher doses. METHODS: We escalated the total dose for the improvement of local control for large tumors. In this study, 71 patients underwent SBRT between December 2008 and April 2014. Isocenter doses of 48, 50, and 52 Gy were administered for tumors with a longest diameter of < 1.5 cm, 1.5-3 cm, and > 3 cm, respectively. It was recommended to cover 95% of the PTV with at least 90% of the isocenter dose, and in all but one cases, 95% of the PTV received at least 80% of the prescribed dose. Treatments were delivered in 4 fractions, giving 2 fractions per week. SBRT was performed with 6-MV photons using 4 non-coplanar and 3 coplanar beams. RESULTS: The median follow-up period was 44 months for all patients and 61 months for living patients. Overall survival (OS) was 65%, progression-free survival (PFS) was 55%, and cumulative incidence of local recurrence (LR) was 15% at 5 years. The 5-year OS was 69% for 57 stage IA patients and 53% for 14 stage IB patients (p = 0.44). The 5-year PFS was 55 and 54%, respectively (p = 0.98). The 5-year cumulative incidence of LR was 11 and 31%, respectively (p = 0.09). The cumulative incidence of Grade ≥ 2 radiation pneumonitis was 25%. CONCLUSIONS: Our newer SBRT study yielded reasonable local control and overall survival and acceptable toxicity, but escalating the total dose did not lead to improved outcomes. TRIAL REGISTRATION: UMIN000027231 , registered on 3 May 2017. Retrospectively registered.

Effects of audio coaching and visual feedback on the stability of respiration during radiotherapy.

PURPOSE: The aim of this study is to compare the respiration-stabilizing abilities of audio coaching (AC) and AC with visual feedback (VF) with that of free breathing (FB). MATERIALS AND METHODS: Ten healthy volunteers were told to breathe in FB, under AC and under AC + VF in random order. The standard deviation (SD) values of the respiratory cycle, the amplitude, the lowest points (exhalation), and the highest points (inhalation) of respiratory wave were used as indices of respiratory stability. RESULTS: Compared with FB, the AC method significantly improved respiratory cycle stability (p = 0.001). The AC + VF method improved the stability of the respiratory cycle, the amplitude and the lowest point of respiratory wave (all p < 0.001). In analyses of each subject's data, compared with FB, the AC method significantly improved the respiratory cycle stability in five subjects, and the AC + VF method improved the stability of the respiratory cycle, the amplitude and the lowest point of respiratory wave in 4, 5, and 4 subjects, respectively. In two cases, coaching did not improve respiratory stability. CONCLUSION: The AC + VF method had the most beneficial effects on respiratory stability. However, coaching is not necessarily effective in all cases. Therefore, the most suitable method should be chosen on an individual basis.

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

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.

The Fate of Residual Tumor Masses That Persist After Stereotactic Body Radiotherapy for Solitary Lung Nodules: Will They Recur?

BACKGROUND: After stereotactic body radiotherapy (SBRT) to the lung, radiation pneumonitis and fibrotic changes often develop, and the tumor shadow usually becomes indistinguishable from the fibrotic shadow. Occasionally, however, a residual mass in patients with no or mild radiation pneumonitis will be observed on serial computed tomography (CT) scans. The purpose of the present study was to evaluate the fate of such residual masses and, if possible, to determine the types of tumor at increased risk of local recurrence. PATIENTS AND METHODS: A total of 50 patients (underlying disease: primary lung cancer in 45, local recurrence in 2, and metastasis in 3) were selected because they had been followed up for > 2 years or until death and had observable CT changes and measurable tumor size for > 1 year, regardless of the influence of radiation pneumonitis. The patients' outcomes were compared according to various patient and tumor characteristics, including the presence and absence of emphysema, tumor size, and tumor shrinkage rate. The median follow-up period was 52 months. RESULTS: Of the 50 patients, only 8 developed local recurrence. The local control rate was 81% at 3 years and 73% at 5 years. The local control rates were similar between patients with a high tumor shrinkage rate and those with a low rate. The patients with emphysema exhibited a lower local control rate. CONCLUSION: The persistence of lung masses for > 1 year after SBRT is not necessarily indicative of an increased risk of local recurrence. A low tumor shrinkage rate also was not predictive of recurrence.

Partial-brain radiotherapy for primary central nervous system lymphoma: multi-institutional experience.

Whole-brain radiotherapy (WBRT) has been an important component of treatment for primary central nervous system lymphoma (PCNSL), but delayed neurotoxicity has been a matter of concern. We have employed partial-brain radiotherapy (PBRT) with wide margins for PCNSL patients with a single lesion or a few lesions. In this study, we evaluated the treatment outcome in PCNSL patients undergoing PBRT. Between 2003 and 2014, 24 patients were treated with PBRT; 16 received high-dose-methotrexate (MTX) -containing chemotherapy before PBRT. Conventional fractionation with a median dose of 54 Gy was used. For reference, 15 patients undergoing MTX-based chemotherapy and WBRT were also analyzed. The 3-year overall survival rate was 60% for all 24 patients undergoing PBRT and 68% for the 16 patients undergoing MTX-based chemotherapy plus PBRT. The 3-year progression-free survival rate was 41% for all 24 patients undergoing PBRT and 36% for the 16 patients undergoing MTX-based chemotherapy. The in-field recurrence rate was 26% and the out-of-field recurrence rate was 15% at 3 years for all 24 patients undergoing PBRT. The rates for in-field recurrence and the out-of-field recurrence were 27% and 21%, respectively, for the 16 patients undergoing MTX-based chemotherapy. CNS-recurrence rates were similar in patients undergoing MTX-based chemotherapy and PBRT to the rates in those undergoing MTX-based chemotherapy and WBRT. Neurocognitive dysfunction developed in 3 of the 16 patients undergoing MTX + PBRT and in 4 of 15 patients undergoing MTX + WBRT (P = 0.68). PBRT seems to be a feasible treatment option for solitary PCNSL. Further investigations are warranted to evaluate the advantages of PBRT over WBRT.

Stereotactic body radiotherapy using a radiobiology-based regimen for stage I non-small-cell lung cancer: five-year mature results.

INTRODUCTION: Although the protocol of 48 Gy in four fractions over 4 days has been most often employed in stereotactic body radiotherapy (SBRT) for stage I non-small-cell lung cancer in Japan, higher doses are necessary to control larger tumors, and interfraction intervals should be longer than 24 hours to take advantage of reoxygenation. We report the final results of our study testing the following regimen: for tumors less than 1.5, 1.5-3, and greater than 3 cm in diameter, 44, 48, and 52 Gy, respectively, were given in four fractions with interfraction intervals of greater than or equal to 3 days. METHODS: Among 180 histologically proven patients entered, 120 were medically inoperable and 60 were operable. The median patient age was 77 years (range, 29-89). SBRT was performed with 6-MV photons using four noncoplanar and three coplanar beams. Isocenter doses of 44, 48, and 52 Gy were given to four, 124, and 52 patients, respectively. RESULTS: The 5-year overall survival rate was 52.2% for all 180 patients and 66% for 60 operable patients. The 5-year local control rate was 86% for tumors less than or equal to 3 cm (44/48 Gy) and 73% for tumors greater than 3 cm (52 Gy; p = 0.076). Grade greater than or equal to 2 radiation pneumonitis developed in 13% (10% for the 44/48-Gy group and 21% for the 52-Gy group; p = 0.056). Other grade 2 toxicities were all less than 4%. CONCLUSIONS: Our first prospective SBRT study yielded reasonable local control and overall survival rates and acceptable toxicity. Refinement of the protocol including dose escalation may lead to better outcome.

Changes in volume of stage I non-small-cell lung cancer during stereotactic body radiotherapy.

BACKGROUND: The overall treatment time of stereotactic body radiotherapy (SBRT) for non-small-cell lung cancer is usually 3 to over 10 days. If it is longer than 7 days, tumor volume expansion during SBRT may jeopardize the target dose coverage. In this study, volume change of stage I NSCLC during SBRT was investigated. METHODS: Fifty patients undergoing 4-fraction SBRT with a total dose of 48 Gy (n = 36) or 52 Gy (n = 14) were analyzed. CT was taken for registration at the first and third SBRT sessions with an interval of 7 days in all patients. Patient age was 29-87 years (median, 77), and 39 were men. Histology was adenocarcinoma in 28, squamous cell carcinoma in 17, and others in 5. According to the UICC 7th classification, T-stage was T1a in 9 patients, T1b in 27, and T2a in 14. Tumor volumes on the first and 8th days were determined on CT images taken during the exhalation phase, by importing the data into the Dr. View/LINAX image analysis system. After determining the optimal threshold for distinguishing tumor from pulmonary parenchyma, the region above -250 HU was automatically extracted and the tumor volumes were calculated. RESULTS: The median tumor volume was 7.3 ml (range, 0.5-35.7) on day 1 and 7.5 ml (range, 0.5-35.7) on day 8. Volume increase of over 10% was observed in 16 cases (32%); increases by >10 to ≤ 20%, >20 to ≤ 30%, and >30% were observed in 9, 5, and 2 cases, respectively. The increase in the estimated tumor diameter was over 2 mm in 3 cases and 1-2 mm in 6. A decrease of 10% or more was seen in 3 cases. Among the 16 tumors showing a volume increase of over 10%, T-stage was T1a in 2 patients, T1b in 9, and T2a in 5. Histology was adenocarcinoma in 10 patients, squamous cell carcinoma in 5, and others in 1. CONCLUSIONS: Volume expansion >10% was observed in 32% of the tumors during the first week of SBRT, possibly due to edema or sustained tumor progression. When planning SBRT, this phenomenon should be taken into account.

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

Organizing pneumonia after stereotactic ablative radiotherapy of the lung.

BACKGROUND: Organizing pneumonia (OP), so called bronchiolitis obliterans organizing pneumonia after postoperative irradiation for breast cancer has been often reported. There is little information about OP after other radiation modalities. This cohort study investigated the clinical features and risk factors of OP after stereotactic ablative radiotherapy of the lung (SABR). METHODS: Patients undergoing SABR between 2004 and 2010 in two institutions were investigated. Blood test and chest computed tomography were performed at intervals of 1 to 3 months after SABR. The criteria for diagnosing OP were: 1) mixture of patchy and ground-glass opacity, 2) general and/or respiratory symptoms lasting for at least 2 weeks, 3) radiographic lesion in the lung volume receiving < 0.5 Gy, and 4) no evidence of a specific cause. RESULTS: Among 189 patients (164 with stage I lung cancer and 25 with single lung metastasis) analyzed, nine developed OP. The incidence at 2 years was 5.2% (95% confidence interval; 2.6-9.3%). Dyspnea were observed in all patients. Four had fever. These symptoms and pulmonary infiltration rapidly improved after corticosteroid therapy. Eight patients had presented with symptomatic radiation pneumonitis (RP) around the tumor 2 to 7 months before OP. The prior RP history was strongly associated with OP (hazard ratio 61.7; p = 0.0028) in multivariate analysis. CONCLUSIONS: This is the first report on OP after SABR. The incidence appeared to be relatively high. The symptoms were sometimes severe, but corticosteroid therapy was effective. When patients after SABR present with unusual pneumonia, OP should be considered as a differential diagnosis, especially in patients with prior symptomatic RP.

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

BACKGROUND: Radiation 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. METHODS: Between 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. RESULTS: The 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%). CONCLUSIONS: After 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.

Stereotactic body radiotherapy using a radiobiology-based regimen for stage I nonsmall cell lung cancer: a multicenter study.

BACKGROUND: The most common regimen of stereotactic body radiotherapy (SBRT) for stage I nonsmall cell lung cancer in Japan is 48 grays (Gy) in 4 fractions over 4 days. Radiobiologically, however, higher doses are necessary to control larger tumors, and interfraction intervals should be >24 hours to take advantage of reoxygenation. In this study, the authors tested the following regimen: For tumors that measured <1.5 cm, 1.5 to 3.0 cm, and >3.0 cm in greatest dimension, radiation doses of 44 Gy, 48 Gy, and 52 Gy, respectively, were given in 4 fractions with interfraction intervals of ≥3 days. METHODS: Among 180 patients with histologically proven disease who entered the study, 120 were medically inoperable, and 60 were operable. The median patient age was 77 years (range, 29-92 years). SBRT was performed with 6-megavolt photons using 4 noncoplanar beams and 3 coplanar beams. Isocenter doses of 44 Gy, 48 Gy, and 52 Gy were received by 4 patients, 124 patients, and 52 patients, respectively. RESULTS: The overall survival rate for all 180 patients was 69% at 3 years and 52% at 5 years. The 3-year survival rate was 74% for operable patients and 59% for medically inoperable patients (P = .080). The 3-year local control rate was 86% for tumors ≤3 cm (44/48 Gy) and 73% for tumors >3 cm (52 Gy; P = .050). Grade ≥2 radiation pneumonitis developed in 13% of patients (10% of the 44-Gy/48-Gy group and 21% of the 52-Gy group; P = .056). All other grade 2 toxicities developed in <4% of patients. CONCLUSIONS: The SBRT protocol used in this study yielded reasonable local control and overall survival rates and acceptable toxicity. Dose escalation is being investigated.

Progression of non-small-cell lung cancer during the interval before stereotactic body radiotherapy.

PURPOSE: To investigate the relationship between waiting time (WT) and disease progression in patients undergoing stereotactic body radiotherapy (SBRT) for lung adenocarcinoma (AD) or squamous cell carcinoma (SQ). METHODS AND MATERIALS: 201 patients with Stage I AD or SQ undergoing SBRT between January 2004 and June 2010 were analyzed. The WT was defined as the interval between diagnostic computed tomography before referral and computed tomography for treatment planning or positioning before SBRT. Tumor size was measured on the slice of the longest tumor diameter, and tumor volume was calculated from the longest diameter and the diameter perpendicular to it. Changes in tumor volume and TNM stage progression were evaluated, and volume doubling time (VDT) was estimated. RESULTS: The median WT was 42 days (range, 5-323 days). There was a correlation between WT and rate of increase in volume in both AD and SQ. The median VDTs of AD and SQ were 170 and 93 days, respectively. Thirty-six tumors (23%) did not show volume increase during WTs >25 days. In 41 patients waiting for ≤4 weeks, no patient showed T stage progression, whereas in 25 of 120 (21%) patients waiting for >4 weeks, T stage progressed from T1 to T2 (p = 0.001). In 10 of 110 (9.1%) T1 ADs and 15 of 51 (29%) T1 SQs, T stage progressed (p = 0.002). N stage and M stage progressions were not observed. CONCLUSION: Generally, a WT of ≤4 weeks seems to be acceptable. The WT seems to be more important in SQ than in AD.

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.

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.