Search

Background/purpose: The long-term clinical impact of prostate position-based image-guided radiotherapy (IGRT) for localized prostate cancer remains unclear. Materials and methods: We retrospectively compared clinical outcomes following intensity-modulated radiation therapy (IMRT) with cone-beam computed tomography-based prostate position-based IGRT (P-IGRT) or without P-IGRT (non-P-IGRT). From June 2011, we applied P-IGRT in IMRT for intermediate-risk (IR) prostate cancer (PCa) (D'Amico risk classification) (76 Gy in 38 fractions, with smaller margins). Clinical outcomes of patients who received P-IGRT between June 2011 and June 2019 were retrospectively compared with those of patients with IR PCa who received IMRT without P-IGRT between October 2002 and May 2011 in our institution (74 Gy in 37 fractions). Results: A total of 222 consecutive patients were analyzed: 114 in the P-IGRT cohort and 108 in the non-P-IGRT cohort. The median follow-up period after IMRT was 7.1 years for the P-IGRT cohort and 10.8 years for the non-P-IGRT cohort. The biochemical failure-free rate was significantly better in the P-IGRT cohort (94.9% for the P-IGRT cohort vs 82.7% for the non-P-IGRT cohort at 10 years, p = 0.041). The rate of rectal bleeding which needs intervention including the use of suppositories was significantly lower in the P-IGRT cohort (p < 0.001). Conclusions: The use of P-IGRT with higher doses and smaller margins was correlated with significantly better biochemical control, and a lower incidence of rectal bleeding in IMRT for intermediate-risk prostate cancer. The enhanced accuracy using P-IGRT has the potential to independently improve disease control and reduce late rectal bleeding. [ABSTRACT FROM AUTHOR]

Background: The current standard of care for patients with unresectable locally advanced non-small cell lung cancer (NSCLC) is chemoradiotherapy (CRT) combined with durvalumab consolidation therapy. However, radiotherapy (RT) always carries the risk of radiation pneumonitis (RP), which can preclude durvalumab continuation. In particular, the spread of interstitial lung disease (ILD) in low-dose areas or extending beyond the RT field often makes it difficult to determine the safety of continuation or rechallenging of durvalumab. Thus, we retrospectively analyzed ILD/RP after definitive RT with and without durvalumab, with assessment of radiologic features and dose distribution in RT. Methods: We retrospectively evaluated the clinical records, CT imaging, and radiotherapy planning data of 74 patients with NSCLC who underwent definitive RT at our institution between July 2016 and July 2020. We assessed the risk factors for recurrence within one year and occurrence of ILD/RP. Results: Kaplan-Meier method showed that ≥ 7 cycles of durvalumab significantly improved 1-year progression free survival (PFS) (p < 0.001). Nineteen patients (26%) were diagnosed with ≥ Grade 2 and 7 (9.5%) with ≥ Grade 3 ILD/RP after completing RT. There was no significant correlation between durvalumab administration and ≥ Grade 2 ILD/RP. Twelve patients (16%) developed ILD/RP that spread outside the high-dose (> 40 Gy) area, of whom 8 (67%) had ≥ Grade 2 and 3 (25%) had Grade 3 symptoms. In unadjusted and multivariate Cox proportional-hazards models adjusted for V20 (proportion of the lung volume receiving ≥ 20 Gy), high HbA1c level was significantly correlated with ILD/RP pattern spreading outside the high-dose area (hazard ratio, 1.842; 95% confidence interval, 1.35–2.51). Conclusions: Durvalumab improved 1-year PFS without increasing the risk of ILD/RP. Diabetic factors were associated with ILD/RP distribution pattern spreading in the lower dose area or outside RT fields, with a high rate of symptoms. Further study of the clinical background of patients including diabetes is needed to safely increase the number of durvalumab doses after CRT. [ABSTRACT FROM AUTHOR]

Background: Several studies have confirmed a dosimetric advantage associated with use of a smaller leaf in intensity-modulated radiation therapy (IMRT). However, no studies have identified any clinical benefits. We investigated the effect of a smaller multileaf collimator (MLC) width on the onset of late rectal bleeding after high-dose prostate IMRT. Materials and methods: Two hundred and five prostate cancer patients were treated with a total dose of 78 Gy in 39 fractions by use of a dynamic MLC technique; however, two different MLC were used: a 10-mm-wide device and a 5-mm-wide device. Gastrointestinal toxicity and several clinical factors were assessed. Results: The 5-year actuarial risk of grade 2 or higher rectal bleeding was 6.9 % for the 10-mm-wide group ( n = 132) and 1.8 % for the 5-mm-wide group ( n = 73) ( p = 0.04). The median estimated rectal doses for the two groups were 55.1 and 50.6 Gy ( p < 0.001), respectively. Univariate analysis showed that acute toxicity, rectal V30-60, median rectal dose, normal tissue complication probability (NTCP), and MLC type were significant predictive factors for late rectal toxicity. In multivariate analysis, acute toxicity and NTCP remained significant. Conclusion: In our planning approach for prostate IMRT, a decrease in MLC width from 10 to 5 mm contributed to further rectal dose reduction, which was the most important predictor of late rectal toxicity. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the clinical effectiveness of pretreatment [(18)F] fluoro-2-deoxy-d-glucose-positron emission tomography for head-and-neck squamous cell carcinoma patients with nodal metastasis treated with chemoradiotherapy. Methods and Materials: Between March 2002 and December 2006, 178 patients with head-and-neck squamous cell carcinoma and nodal metastasis underwent fluoro-2-deoxy-d-glucose positron emission tomography before chemoradiotherapy. Fluoro-2-deoxy-d-glucose uptake by both the primary lesion and the neck node was measured using the standard uptake value (SUV). The overall survival, disease-free survival, local control, nodal progression-free survival, and distant metastasis-free survival rates were calculated, and several prognostic factors were evaluated. Results: The patients with a nodal SUV ≥6.00 had a significantly lower 3-year disease-free survival rate than those with a lower SUV (44% vs. 69%, p = .004). On multivariate analysis, a high SUV of nodal disease also proved to be a significantly unfavorable factor for disease-free survival (p = .04, 95% confidence interval [CI], 1.02–3.23), nodal progression-free survival (p = .05; 95% CI, 1.00–4.15), and distant metastasis-free survival (p = .016; 95% CI, 1.25–8.92). Among the patients with a greater nodal SUV (≥6.00), those treated with planned neck dissection had better nodal progression-free survival than those in the observation group (p = .04, hazard ratio, 2.36; 95% CI, 1.00–5.85). Conclusion: Among head-and-neck squamous cell carcinoma patients treated with chemoradiotherapy, the pretreatment SUV of nodal disease was one of the strongest prognostic factors and also provided important information for the selection of patients suitable for planned neck dissection. [ABSTRACT FROM AUTHOR]

Background: Management of pelvic node‐positive prostate cancer has been challenging and controversial. We conducted a study to evaluate the outcomes of whole‐pelvic (WP) simultaneous integrated boost (SIB) intensity‐modulated radiation therapy (IMRT) combined with androgen deprivation therapy (ADT). Methods: A total of 67 consecutive patients with cT1c‐4N1M0 prostate cancer were definitively treated by WP SIB‐IMRT. Neoadjuvant ADT (median: 8.3 months) was administered in all cases. WP SIB‐IMRT was designed to simultaneously deliver 78, 66.3, and 58.5 Gy in 39 fractions to the prostate plus seminal vesicles, metastatic lymph nodes (LNs), and the pelvic LN region, respectively. Adjuvant ADT (median: 24.7 months) was administered in 66 patients. Results: The median follow‐up period was 81.6 months (range: 30.5–160.7). Biochemical relapse‐free, overall, and prostate cancer‐specific survival rates at 10 years were 59.8%, 79.6%, and 86.3%, respectively. Loco‐regional recurrence was not observed. Being in International Society of Urological Pathology grade group 5 and having a posttreatment detectable nadir prostate‐specific antigen (PSA) level (≥0.010 ng/ml) were significantly associated with worse prostate cancer‐specific survival and progression of castration resistance. The 10‐year cumulative incidence rates of grade 2 and 3 late toxicities were, respectively, 1.5% and 0% for genitourinary, 0% and 1.5% for gastrointestinal events. No grade 4 acute or late toxicities were observed. Conclusions: WP SIB‐IMRT can be safely administered to patients with pelvic node‐positive prostate cancer. Since grade group 5 and detectable nadir PSA levels are risks for castration resistance, we may need to increase the intensity of treatment for such cases. [ABSTRACT FROM AUTHOR]

Conclusions: Distant metastasis was a major pattern of recurrence after postoperative radiotherapy (PORT) for squamous cell carcinoma (SCC) of the oropharynx, hypopharynx, and larynx. PORT provided good loco-regional control, with tolerable toxicities. Advanced pT and pN were unfavorable prognostic factors. Objective: To determine the clinical outcomes, and the patterns and risk factors for recurrence of SCCs of the oropharynx, hypopharynx, and larynx treated with surgery and PORT. Methods: We retrospectively reviewed 84 patients who received PORT after definitive surgery for SCC of the oropharynx, hypopharynx, or larynx between 2000 and 2010. The primary sites were the oropharynx in 25 patients, hypopharynx in 47 patients, and larynx in 12 patients. Results: The 3-year overall survival (OS), progression-free survival (PFS), and loco-regional control (LRC) rates were 64.9%, 56.7%, and 92.1%, respectively. Recurrences were observed in 27 patients: 6 patients had loco-regional recurrence and 23 patients developed distant metastasis. On multivariate analysis, pT4 and pN2c-N3 displayed significantly worse effects on OS ( p = 0.02 and p < 0.01, respectively) and PFS ( p = 0.02 and p < 0.001, respectively). In the acute phase, 12 patients experienced grade 3 or 4 toxicities. There were no grade 5 toxicities. Late grade 3 toxicity developed in six patients and no grade 4 or 5 toxicities were observed. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to evaluate the effects of treatment with both three-dimensional radiotherapy (3DRT) and weekly 40-mg/m2 cisplatin on postoperative uterine cervical cancer patients with high-risk prognostic factors. Methods: We conducted a retrospective multi-institutional chart review of postoperative uterine cervical cancer patients with high-risk prognostic factors who had been treated with both 3DRT and weekly 40-mg/m2 cisplatin from 2007 to 2012. Each participating hospital provided detailed information regarding patient characteristics, treatment outcomes, and treatment complications. Results: The eligible 96 patients were analyzed. The median follow-up period was 61 months. The 3-year relapse-free survival, overall survival (OS), and locoregional relapse-free survival (LRFS) rates were 76%, 90%, and 88%, respectively. In multivariate analysis, the histological finding of either adenocarcinoma or adenosquamous carcinoma was a significant risk factor for both OS and LRFS. The percentage of patients with grade ≥ 3 acute hematologic toxicity, acute lower gastrointestinal toxicity (GIT), and late lower GIT were 45%, 19%, and 17%, respectively. Conclusions: The outcomes of concurrent chemoradiotherapy (CCRT) using weekly 40-mg/m2 cisplatin are similar to those in the previous studies that used several chemotherapy regimens. However, postoperative CCRT using 3DRT had a high level of late GIT. [ABSTRACT FROM AUTHOR]

Background: We aimed to analyze the 10-year outcomes of intensity-modulated radiation therapy (IMRT) combined with neoadjuvant hormonal therapy (HT) for patients with intermediate- and high-risk T1c-T2N0M0 prostate cancer. Methods: Fifty patients with T1c-T2N0M0 prostate cancer, who were treated with high-dose IMRT combined with neoadjuvant HT, were evaluated. Of these patients, 19 and 31 were classified into the intermediate- and high-risk groups, respectively. Neoadjuvant HT was administered over a median duration of 6 months; 74 and 78 Gy in 2 Gy per fraction were essentially delivered to the intermediate- and high-risk cases, respectively. Adjuvant HT was not administered to any of the patients after the completion of IMRT. Results: Over a median follow-up period of 118 months, the 10-year prostate-specific antigen failure-free survival, prostate-specific antigen failure-free, salvage hormonal therapy-free, prostate cancer-specific survival, and overall survival rates were 70.2 %, 78.7 %, 89.2 %, 100 %, and 88.8 %, respectively. No grade 3 or higher acute or late toxicities were observed. The 10-year likelihoods of developing grade 2 late urinary and rectal toxicities were 13.7 % and 4.2 %, respectively. Compared with the outcomes of a cohort of historical controls who were locally irradiated with 70 Gy by three-dimensional conformal radiotherapy, the prostate-specific antigen failure-free rate was significantly better in the IMRT groups (78.7 % vs. 53.4 % at 10 years; p = 0.027). Conclusions: High-dose IMRT combined with neoadjuvant HT achieved not only high prostate-specific antigen control, but also excellent survival outcomes with acceptable morbidities, for a Japanese cohort of intermediate- and high-risk T1c-T2N0M0 prostate cancer patients, and these results warrant further investigation. [ABSTRACT FROM AUTHOR]

Background: Long-term outcomes of dose-escalated intensity-modulated radiation therapy (IMRT) combined with neoadjuvant (NA) androgen deprivation therapy (ADT) under an early salvage policy in patients with locally advanced prostate cancer (LAPC) were evaluated. Methods: Data from 120 patients with T3-T4N0M0 adenocarcinoma of the prostate treated with IMRT were analyzed. NA-ADT with a median duration of 6 months was provided in all cases. Seventy-eight Gy, at 2 Gy per fraction, was delivered to the prostate and seminal vesicles. Adjuvant ADT (A-ADT) was not provided for any patient following the completion of IMRT. Salvage ADT (S-ADT) commenced when PSA values >4 ng/ml. Results: The median follow-up period was 97 months. S-ADT was initiated in 39 patients. The median PSA value at the initiation of S-ADT was 5.7 ng/ml. The 8-year biochemical relapse-free survival, prostate cancer-specific survival, overall survival and S-ADT-free rates were 53.2 % [95 % confidence interval (CI) 43.4, 62.1], 96.6 % (95 % CI 91.2, 98.7), 89.1 % (95 % CI 81.5, 93.7) and 66.6 % (95 % CI 60, 74.6), respectively. The estimated 8-year cumulative incidence rates of grade 2-3 late gastrointestinal, and grade 2-3 genitourinary toxicity were 7.6 and 10.7 %, respectively. No grade 4 toxicity was observed. Conclusions: High-dose IMRT, combined with NA-ADT for LAPC, was associated with favorable long-term disease-specific and overall survival outcomes, despite non-provision of A-ADT under the early S-ADT provision policy. This approach may represent a viable alternative to uniform provision of long-term A-ADT, because two-thirds of the patients maintained ADT-free status over an 8-year period after IMRT. Prospective trials will be required. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the clinical effectiveness of pretreatment [18F] fluoro-2-deoxy-D-glucose-positron emission tomography for head-and-neck squamous cell carcinoma patients with nodal metastasis treated with chemoradiotherapy. Methods and Materials: Between March 2002 and December 2006, 178 patients with head-and-neck squamous cell carcinoma and nodal metastasis underwent fluoro-2-deoxy-D-glucose positron emission tomography before chemoradiotherapy. Fluoro-2-deoxy-D-glucose uptake by both the primary lesion and the neck node was measured using the standard uptake value (SUV). The overall survival, disease-free survival, local control, nodal progression-free survival, and distant metastasis-free survival rates were calculated, and several prognostic factors were evaluated. Results: The patients with a nodal SUV≥6.00 had a significantly lower 3-year disease-free survival rate than those with a lower SUV (44% vs. 69%, p=.004). On multivariate analysis, a high SUV of nodal disease also proved to be a significantly unfavorable factor for disease-free survival (p=.04, 95% confidence interval [CI], 1.02-3.23), nodal progression-free survival (p=.05; 95% CI, 1.00-4.15), and distant metastasis-free survival (p=.016; 95% CI, 1.25-8.92). Among the patients with a greater nodal SUV (≥6.00), those treated with planned neck dissection had better nodal progression-free survival than those in the observation group (p=.04, hazard ratio, 2.36; 95% CI, 1.00-5.85). Conclusion: Among head-and-neck squamous cell carcinoma patients treated with chemoradiotherapy, the pretreatment SUV of nodal disease was one of the strongest prognostic factors and also provided important information for the selection of patients suitable for planned neck dissection. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: To evaluate the clinical efficacy of definitive radiotherapy for patients with superficial esophageal cancer. Material and methods: From 1990 through 2006, 97 patients with stage I disease were treated with radiotherapy with or without chemotherapy. All patients were diagnosed with panesophagoscopy and computed tomography. Chemotherapy was added in 61 patients, and intra-cavitary brachytherapy (ICBT) was used in 27 patients. Results: The patients were 90 men and seven women with a median age of 65.7years (range; 41–89). At last follow-up with a median follow-up duration of 35.7months, 3year-overall and progression-free survival (PFS) rates were 81.5% (95% C.I.=73.3–89.7%) and 55.8% (95% C.I.=45.2–66.4%), respectively. Shorter tumor length was a significantly favorable factor for the PFS rate (P =0.02) and local failure-free (LFF) rate (P =0.007) on both univariate and multivariate analyses. Although the addition of ICBT had no apparent benefit for survival or tumor control, the rate of severe adverse effects including lethal esophageal ulcers, showed a higher tendency in patients receiving ICBT. Conclusions: Our results regarding efficacy from the viewpoint of organ preservation are promising. Special care would be taken for the use of ICBT for patients with superficial esophageal cancer, especially if they have received chemoradiotherapy. [Copyright &y& Elsevier]

Purpose: To review the treatment outcomes of limited-stage small-cell lung cancer (LS-SCLC) patients and to compare the outcomes among three groups in which the total radiation doses were 45 Gy with accelerated hyperfractionation (AHF), <54 Gy with standard fractionation (SF), and ≥54 Gy with SF. Methods and Materials: LS-SCLC patients that had been treated with chemoradiotherapy between 1997 and 2007 at Aichi Cancer Center Hospital were reviewed in this study. Of the 127 eligible patients, there were 37 patients in the AHF group, 29 in the SF <54 Gy group, and 61 in the SF ≥54 Gy group. Results: Fifty-five patients (43%) were alive at the time of this analysis, and the median follow-up time of the surviving patients was 33 months. The median survival times were 30.0 months (95% confidence interval [CI] 16.3–43.7) for the AHF group, 14.0 months (CI 6.6–21.4) for the SF <54 Gy group, and 41.0 months (CI 33.9–48.1) for the SF ≥ 54 Gy group. As for the local control rates, and the overall and progression-free survival rates, all outcomes were significantly lower in the SF <54 Gy group than in the other two groups, although no significant difference was found between the AHF and SF ≥54 Gy groups. Conclusions: These results suggest the importance of a high dose of radiation when using once-daily regimen. This study will support future prospective studies to establish optimal radiation doses and fractionation. [Copyright &y& Elsevier]

Purpose: To assess the feasibility of helical tomotherapy (HT) for patients with nasopharyngeal carcinoma. Methods and Materials: From June 2006 to June 2007, 20 patients with nasopharyngeal carcinoma were treated with HT with (n = 18) or without (n = 2) systemic chemotherapy. The primary tumor and involved lymph node (PTV1) were prescribed 70 Gy and the prophylactic region 54 Gy at D95, respectively. The majority of patients received 2 Gy per fraction for PTV1 in 35 fractions. Parotid function was evaluated using quantitative scintigraphy at pretreatment, and posttreatment at 3 months and 1 year later. Results: The median patient age was 53 years, ranging from 15 to 83. Our cohort included 5, 8, 4, 2, and 1 patients with disease Stages IIB, III, IVA, IVB, and IVC, respectively. Histopathological record revealed two for World Health Organization Type I and 18 for Type 2 or 3. The median duration time for treatment preparation was 9.5 days, and all plans were thought to be acceptable regarding dose constraints of both the planning target volume and organ at risk. All patients completed their treatment procedure of intensity-modulated radiation therapy (IMRT). All patients achieved clinical remission after IMRT. The majority of patients had Grade 3 or higher toxicity of skin, mucosa, and neutropenia. At the median follow-up of 10.9 months, two patients recurred, and one patient died from cardiac disease. Parotid gland function at 1 year after completion of IMRT was significantly improved compared with that at 3 months. Conclusion: HT was clinically effective in terms of IMRT planning and utility for patients with nasopharyngeal cancer. [Copyright &y& Elsevier]

Abstract: Purpose: To report the feasibility of dynamic conformal arc radiotherapy with rectum hollow-out technique (DCAT-HO) for localized prostate cancer. Methods and materials: Between October 2000 and April 2007, 204 patients with clinically localized or locally advanced prostate cancer were treated with DCAT-HO. All patients were given neoadjuvant total androgen deprivation (AD) therapy (median 6 months, range 2–27 months). All patients with T3 or T4 stage received post-irradiation AD for 24 months. A total of 128 patients (63%) were treated with 70Gy, and 76 patients (37%) were treated with 74Gy. Acute and late toxicities were scored by the Radiation Therapy Oncology Group morbidity grading scales. PSA relapse was defined as three successive PSA elevations after a post-treatment nadir. The median follow-up was 37 months. Results: Both the acute Grade 2 rectal and urinary toxicities were 1.0%, and no patients experienced acute Grade 3 or higher symptoms. The 3-year rates of both ⩾ late Grade 2 rectal and urinary toxicities were 3.4%. The 3-year PSA relapse-free survival for low, intermediate, and high-risk group patients treated with 70 Gy were 54%, 75%, and 87%, respectively. Conclusions: These findings demonstrate the feasibility of DCAT-HO in a large number of patients with short follow-up. DCAT-HO reduced the volume of the rectum exposed to higher doses and this led to an overall reduction in late rectal toxicity. [Copyright &y& Elsevier]

Purpose: To assess the efficacy of alternating chemoradiotherapy combined with extended-field conformal radiotherapy for patients with high-risk cervical cancer. Methods and Materials: Patients with previously untreated cervical cancer, with Stage III/IVA disease, or Stage IB/II with high-risk factor (primary tumor diameter ≥50 mm or positive lymph node) were entered into this study. Three cycles of chemotherapy with 3,500 mg/m2 of 5-fluorouracil (5-FU) and nedaplatin (NDP) were accompanied with pelvic irradiation of 45.6–51.3 Gy in 24–27 fractions over 6 weeks. Prophylactic (36 Gy/20 fractions) or definitive (45–56 Gy) irradiation for para-aortic region was followed by pelvic irradiation. Results: Between 1998 and 2004, 40 patients were recruited for this protocol study. Eighteen patients from Phase I setting were registered. Twenty-two patients were treated with NDP of 140 mg/m2 (the recommended dose) in the Phase II segment. Twenty-five patients had T3 disease, and 25 patients had nodal disease including para-aortic involvement (n = 5). Overall/progression-free survival rates at 5 years were 78.8 and 66.5%, respectively. The median follow-up time was 61.8 months (25.5–106.7). Hematologic and gastrointestinal Grade 3 or more toxicities were relatively high rate (27.5–45%); however, they were well manageable. Two for bladder toxicity of Grade 3 were noted. Comparing the data from historical control group evaluated by magnetic resonance imaging, alternating chemoradiotherapy revealed a significant favorable factor for survival and disease recurrence in multivariate analysis (p < 0.05). Conclusion: Acquired results from our unique protocol for cervical cancer with high-risk factor were thought to be promising, considering that the majority of our cohort consisted of high-risk population. [Copyright &y& Elsevier]

Primarily combined radiotherapy and chemotherapy are used to treat unresectable non-small-cell lung cancer; however, the results are not satisfactory. In this study treatment results were retrospectively analyzed and the prognostic factors related to survival were identified. From March 1999 to January 2004, 102 patients with stage IIIA/IIIB non-small-cell lung cancer received definitive radiotherapy with or without chemotherapy. Radiotherapy involved a daily dose of 1.8–2.0 Gy five times a week; 60 Gy was set as the total dose. Maximal chemotherapy was given to patients with normal kidney, liver, and bone marrow functions. The 5-year overall survival rate was 22.2%; the median survival was 18 months. The median follow-up of surviving patients was 53 months. The complete or partial response rate was 85%. At the time of the last follow-up, 21 patients were alive and 81 patients had died, including 5 patients who had died due to radiation pneumonitis. There were significant differences in survival and in the fatal radiation pneumonitis rate between patients with superior lobe lesions and those with middle or inferior lobe lesions. Patients whose primary tumor is located in the superior lobe appear to have a better clinical outcome. [ABSTRACT FROM AUTHOR]