ABSTRACT
Chemoradiotherapy has been considered as one of the standard treatment options for clinical T1bN0M0 esophageal squamous cell carcinoma with organ preservation. However, 20% of patients develop locoregional recurrence after chemoradiotherapy, which requires salvage treatment including salvage surgery and endoscopic resection. Salvage surgery can cause complications and treatment-related death. Interestingly, chemoradiotherapy with elective nodal irradiation has been reported to reduce the locoregional recurrence of advanced esophageal squamous cell carcinoma. Hence, we are conducting a clinical trial to confirm whether modified chemoradiotherapy with elective nodal irradiation was superiority to that without elective nodal irradiation for the patients with cT1bN0M0 esophageal squamous cell carcinoma. The primary endpoint is major progression-free survival, defined as the time from randomization to the date of death or disease progression, excluding successful curative resection through salvage endoscopic resection. We plan to enroll 280 patients from 54 institutions over 4 years. This trial has been registered in the Japan Registry of Clinical Trials (jRCTs031200067).
Subject(s)
Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Humans , Esophageal Neoplasms/pathology , Esophageal Squamous Cell Carcinoma/therapy , Esophageal Squamous Cell Carcinoma/pathology , Neoplasm Recurrence, Local/pathology , Chemoradiotherapy , Japan , Treatment Outcome , Salvage Therapy , Retrospective StudiesABSTRACT
PURPOSE: This study aimed to assess recurrence patterns and identify the optimal dose and target volumes of postoperative radiotherapy (PORT) in patients with oral cavity squamous cell carcinoma (OSCC). METHODS: Data of 111 patients who received PORT for OSCC between January 2010 and April 2020 were retrospectively reviewed. The median age was 68 years (range 19-88). PORT was administered as initial treatment to 63 patients and as salvage treatment for recurrent tumors to 48 patients. The median prescribed dose was 60â¯Gy (range 50-66) administered in 30 fractions (range 25-33). RESULTS: Median follow-up time was 73 months (range 24-147). Overall survival (OS), progression-free survival (PFS), local control (LC), and locoregional control (LRC) at 3 years were 55.6%, 45.6%, 74.6%, and 63.1%, respectively. There were no significant differences in OS, PFS, LC, and LRC between the initially diagnosed and postoperative recurrent cases. Of 22 patients (20%) who developed regional nodal recurrences, 17 (15%) and 11 (10%) had in-field and out-of-field recurrences, respectively. Of 105 patients who received irradiation to the primary tumor bed, 24 (23%) developed recurrence at the primary site. The PFS and LC rates were significantly worse in patients receiving ≤â¯56â¯Gy to the primary site than those receiving >â¯56â¯Gy (pâ¯= 0.016 and pâ¯= 0.032, respectively). CONCLUSION: PORT was effective for postoperative recurrences as well as for initially diagnosed oral cavity cancer. Doses greater than 56â¯Gy to the primary site may be required in PORT for OSCC.
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PURPOSE: Stereotactic body radiotherapy (SBRT) is a treatment option for early-stage lung cancer. We aimed to examine the differences in failure patterns after SBRT according to the clinical T stage. METHODS: A total of 120 patients with early-stage lung cancer (T1-3N0M0) who underwent SBRT were analysed. The clinical stage in patients whose tumours were in contact with the chest wall was confirmed using four-dimensional computed tomography (4D-CT). Local failure, regional node metastasis, and distant metastasis were confirmed from clinical charts. RESULTS: Median follow-up time was 27.5 months (range 7-122) after SBRT. Thirteen patients were restaged from clinical T2 with visceral pleural invasion to T3 with chest wall invasion using 4D-CT analysis. Thirty-seven patients developed recurrences. The median progression-free survival (PFS) and overall survival (OS) were 38.1 and 53.8 months, respectively. The 3year PFS and OS rates were 50.7% and 60.3%, respectively. A significant difference was observed in PFS according to the clinical T stage (pâ¯= 0.001). No significant differences were observed in OS according to the clinical T stage (pâ¯= 0.213). The proportion of locoregional failures relative to distant metastasis decreased with progression from T1 to T3. The pleural dissemination rate was significantly higher in T3 tumours than in T1 and T2 tumours (pâ¯= 0.010). CONCLUSION: Clinical T stage is associated with PFS after SBRT for lung cancer. There were differences in the failure patterns according to T stage. 4D-CT might provide significant information for assessing chest wall invasion associated with unfavourable PFS.
Subject(s)
Lung Neoplasms , Radiosurgery , Humans , Four-Dimensional Computed Tomography , Radiosurgery/methods , Treatment Outcome , Retrospective Studies , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/radiotherapyABSTRACT
BACKGROUND: This study aimed to reveal the long-term outcomes and late toxicities (> 5 years) after definitive intensity-modulated radiation therapy (IMRT) in patients with nasopharyngeal carcinoma (NPC). METHODS: Data from 43 patients (median age, 55 years; range, 17-72 years) with NPC who underwent definitive IMRT between 2001 and 2018 were analyzed. All patients were alive and disease-free 5 years after IMRT. A total dose of 70 (range, 66-70) Gy was delivered in 35 (33-35) fractions with concurrent cisplatin chemotherapy. RESULTS: The median follow-up duration was 119 (range, 61.5-242.1) months. Three patients developed locoregional failure at 79, 92, and 149 months after IMRT, respectively. Of these, 2 patients died of disease progression at 136 and 153 months after IMRT. One patient died of aspiration pneumonia 141 months after IMRT, despite salvage of the recurrent tumor by re-irradiation. In addition, one patient died of aspiration pneumonia 62 months after the IMRT. Thus, the 10-year overall survival, progression-free survival, and locoregional control rates were 98%, 92%, and 94%, respectively. Grade ≥ 2 and ≥ 3 late toxicities were observed in 28 (65%) and 9 (21%) patients, respectively. Nine second primary cancers, including five tongue cancers and two external auditory canal carcinomas, were observed in seven (16%) patients. CONCLUSION: Late recurrences, severe late toxicities, and second primary cancers were observed > 5 years after IMRT. A long-term follow-up of > 5 years is needed in patients with NPC.
Subject(s)
Nasopharyngeal Neoplasms , Neoplasms, Second Primary , Pneumonia, Aspiration , Radiotherapy, Intensity-Modulated , Humans , Middle Aged , Nasopharyngeal Carcinoma/radiotherapy , Nasopharyngeal Neoplasms/drug therapy , Nasopharyngeal Neoplasms/radiotherapy , Nasopharyngeal Neoplasms/pathology , Neoplasms, Second Primary/pathology , Neoplasm Staging , Neoplasm Recurrence, Local/pathology , Radiotherapy, Intensity-Modulated/adverse effects , Disease Progression , Pneumonia, Aspiration/etiology , Pneumonia, Aspiration/pathologyABSTRACT
Background: We clarified the dose difference between the anisotropic analytical algorithm (AAA) and Acuros XB (AXB) with increasing target's air content using a virtual phantom and clinical cases. Materials and methods: Whole neck volumetric modulated arc therapy (VMAT) plan was transferred into a virtual phantom with a cylindrical air structure at the center. The diameter of the air structure was changed from 0 to 6 cm, and the target's air content defined as the air/planning target volume (PTV) in percent (air/PTV) was varied. VMAT plans were recalculated by AAA and AXB with the same monitor unit (MU) and multi-leaf collimator (MLC) motions. The dose at each air/PTV (5%-30%) was compared between each algorithm with D98%, D95%, D50% and D2% for the PTV. In addition, MUs were also compared with the same MLC motions between the D95% prescription with AAA (AAA_D95%), AXB_D95%, and the prescription to 100% minus air/PTV (AXB_D100%-air/PTV) in clinical cases of head and neck (HNC). Results: When air/PTV increased (5-30%), the dose differences between AAA and AXB for D98%, D95%, D50% and D2% were 3.08-15.72%, 2.35-13.92%, 0.63-4.59%, and 0.14-6.44%, respectively. At clinical cases with air/PTV of 5.61% and 28.19%, compared to AAA_D95%, the MUs differences were, respectively, 2.03% and 6.74% for AXB_D95% and 1.80% and 0.50% for AXB_D100%-air/PTV. Conclusion: The dose difference between AAA and AXB increased as the target's air content increased, and AXB_D95% resulted in a dose escalation over AAA_D95% when the target's air content was ≥ 5%. The D100%-air/PTV of PTV using AXB was comparable to the D95% of PTV using AAA.
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BACKGROUND: This multi-institutional clinical trial evaluated the feasibility of intensity-modulated radiotherapy (IMRT) for patients with locally advanced non-small cell lung cancer (NSCLC). METHODS: The major inclusion criteria were clinical stage III NSCLC, age 20-74 years, and Eastern Cooperative Oncology Group performance status 0-1. Patients were treated with either cisplatin + S-1 (CS; four cycles every 4 weeks) or carboplatin + paclitaxel (CP; administered weekly with thoracic radiotherapy [RT], plus two consolidation cycles) concurrently with IMRT (60 Gy in 30 fractions). The primary endpoint was a treatment completion rate, defined as at least two cycles of CS or five cycles of CP during IMRT and completing 60 Gy IMRT within 56 days after the start of treatment, assumed its 90% confidence interval exceeds 60%. RT quality assurance was mandatory for all the patients. RESULTS: Twenty-two patients were registered. One patient withdrew due to pulmonary infection before starting treatment. RT plans were reviewed and none was judged as a protocol violation. Grade 2 and 3 pneumonitis occurred in four (19%) and one (5%) patients, respectively. Seventeen patients met the primary endpoint, with a treatment completion rate of 77.3% (90% confidence interval [CI] 58.0%-90.6%). Four patients failed to complete chemotherapy due to chemotherapy-related adverse events, but 20 patients completed IMRT. There were no treatment-related deaths. The 2-year progression-free and overall survival rates were 31.8% (95% CI 17.3%-58.7%) and 77.3% (95% CI 61.6%-96.9%), respectively. CONCLUSION: The treatment completion rate did not meet the primary endpoint, but 20 of 22 patients completed IMRT.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Radiotherapy, Intensity-Modulated , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carboplatin , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/radiotherapy , Chemoradiotherapy/adverse effects , Chemoradiotherapy/methods , Cisplatin/therapeutic use , Feasibility Studies , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/radiotherapy , Middle Aged , Paclitaxel/adverse effects , Radiotherapy, Intensity-Modulated/adverse effects , Radiotherapy, Intensity-Modulated/methods , Young AdultABSTRACT
PURPOSE: To determine the thickness of a soft variable shape tungsten rubber (STR) as a lung compensating filter in total body irradiation. METHODS: A tough water (TW) phantom and tough lung (TL) phantom were used as water and lung-equivalent phantoms. The TW with a thickness of 3 cm simulating the thoracic wall was used (upper layer). The TW or TL with a thickness from 1 to 15 cm (1 cm increments) was placed beneath the upper layer (middle layer). The TW with a thickness of 5 cm simulating the mediastinum was placed beneath the middle layer (lower layer), and a farmer ionization chamber was placed beneath this layer. The relative doses of a 10 MV X-rays were then measured. The TL was compensated in 1 mm increments from 1 to 11 mm of the STR, and the thickness of the STR at the same dose of TW (water equivalent) was obtained. RESULTS: The compensating ability of STR increased as the thickness of the TL increased, and an STR with a thickness of 1 mm reduced the dose by 2%-4%, depending on the thickness of lung. The STR thickness as an equivalent dose of TW per cm of TL was approximately linear, and the thickness was 0.62 mm/cm of TL. CONCLUSION: The STR can be used as a lung compensating filter for a water equivalent dose with 0.62 mm of STR per cm of lung.
Subject(s)
Tungsten , Whole-Body Irradiation , Humans , Rubber , Phantoms, Imaging , Water , Lung/radiation effects , Radiotherapy Dosage , Radiometry/methodsABSTRACT
PURPOSE: The efficiency of protective equipment for the brain has not been verified at the left anterior oblique (LAO) position, which is commonly used in clinical procedures. The purpose of this study was to investigate radiation exposure of the brain in interventional radiology (IR) and the shielding ability of a new protective flap. METHODS: We made a flap that combined a protective cap with a left lateral face shield. The flap was made of tungsten-containing rubber (TCR). An anthropomorphic head phantom was placed at the physician's position, and air kerma rates (µGy/min and µGy/15s) were measured by electronic dosimeter at three locations: the surface of the left side of the head, and the left and right temporal lobes with the protective cap and the flap in fluoroscopy and cine modes. The X-ray tube was at the lower left side of the physician, and its angles were LAO60 and LAO60CAU40. The tube voltage (95-125 kV), tube current (4.7-732 mA), and air kerma rate (27.8-1078 mGy/min) were automatically adjusted by the X-ray system. We obtained the cap and the flap shielding efficiencies. RESULTS: In cine mode at LAO60CAU40, the shielding efficiencies on the surface of the left side of the head and left temporal lobe with the cap were 92.6% and 5.1%, respectively, and the corresponding shielding efficiencies with the flap were 92.5% and 86.1%, respectively. The flap can reduce radiation exposure of the brain more than the cap alone. CONCLUSIONS: At the left anterior oblique in interventional radiology, the flap can reduce exposure to the brain.
Subject(s)
Occupational Exposure , Phantoms, Imaging , Physicians , Radiation Exposure , Radiation Protection , Brain/diagnostic imaging , Brain/surgery , Fluoroscopy , Humans , Occupational Exposure/analysis , Occupational Exposure/prevention & control , Radiation Dosage , Radiation Exposure/prevention & control , Radiology, InterventionalABSTRACT
BACKGROUND: Synchronous oligometastatic non-small cell lung cancer (NSCLC) is generally characterised by the limited number of metastases at the time of diagnosis. Several clinical trials have shown that local ablative therapy (LAT) at all sites of the disease might be beneficial for patients with oligometastatic NSCLC. In recent years, the combination of programmed cell death 1 (PD-1) inhibitors or programmed cell death ligand 1 with cytotoxic chemotherapy has become a new standard treatment for patients with metastatic NSCLC. Furthermore, multisite LAT would inherently reduce the overall tumour burden, and this could promote T cell reinvigoration to enhance the efficacy of PD-1 inhibitors. Few studies have evaluated the efficacy of the combination of PD-1 inhibitors with LAT at all sites of disease. The aim of the present multicentre single-arm phase II study is to evaluate the efficacy of LAT at all sites of disease following standard platinum doublet chemotherapy with pembrolizumab in patients with oligometastatic NSCLC. METHODS: Thirty patients with synchronous oligometastatic NSCLC will be enrolled in the trial. All patients will receive 2-4 cycles of a systemic treatment including pembrolizumab and chemotherapy as induction therapy. Patients who will receive LAT will be determined by a multidisciplinary tumour board, including medical oncologists, radiation oncologists, and thoracic surgeons. LAT will be administered at all sites of disease within 21-56 days of the last dose of induction therapy and will be followed by maintenance therapy within 42 days of the last day of LAT. The primary endpoint is the progression-free survival (PFS) rate of 24 months from the date of initiation of LAT. The secondary endpoints are toxicity, response to induction therapy, PFS, overall survival, and the frequency of LAT. DISCUSSION: This study will provide novel data on the efficacy and safety profile of the combination of LAT and chemotherapy plus immune-checkpoint inhibitors in patients with synchronous oligometastatic NSCLC. If the primary endpoint of this study is met, extensive phase III studies further assessing this strategy will be recommended. TRIAL REGISTRATION: jRCT identifier: jRCTs041200046 (date of initial registration: 28 October 2020).
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Immune Checkpoint Inhibitors/therapeutic use , Lung Neoplasms/drug therapy , Adult , Aged , Albumins/administration & dosage , Antibodies, Monoclonal, Humanized/administration & dosage , Antineoplastic Agents, Immunological/administration & dosage , Carboplatin/administration & dosage , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/secondary , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/secondary , Cisplatin/administration & dosage , Drug Administration Schedule , Humans , Induction Chemotherapy/methods , Japan , Lung Neoplasms/pathology , Maintenance Chemotherapy/methods , Middle Aged , Paclitaxel/administration & dosage , Pemetrexed/administration & dosage , Progression-Free SurvivalABSTRACT
BACKGROUND: The current standard treatment for elderly patients with newly diagnosed glioblastoma is surgery followed by short-course radiotherapy with temozolomide. In recent studies, 40 Gy in 15 fractions vs. 60 Gy in 30 fractions, 34 Gy in 10 fractions vs. 60 Gy in 30 fractions, and 40 Gy in 15 fractions vs. 25 Gy in 5 fractions have been reported as non-inferior. The addition of temozolomide increased the survival benefit of radiotherapy with 40 Gy in 15 fractions. However, the optimal regimen for radiotherapy plus concomitant temozolomide remains unresolved. METHODS: This multi-institutional randomized phase III trial was commenced to confirm the non-inferiority of radiotherapy comprising 25 Gy in 5 fractions with concomitant (150 mg/m2/day, 5 days) and adjuvant temozolomide over 40 Gy in 15 fractions with concomitant (75 mg/m2/day, every day from first to last day of radiation) and adjuvant temozolomide in terms of overall survival (OS) in elderly patients with newly diagnosed glioblastoma. A total of 270 patients will be accrued from 51 Japanese institutions in 4 years and follow-up will last 2 years. Patients 71 years of age or older, or 71-75 years old with resection of less than 90% of the contrast-enhanced region, will be registered and randomly assigned to each group with 1:1 allocation. The primary endpoint is OS, and the secondary endpoints are progression-free survival, frequency of adverse events, proportion of Karnofsky performance status preservation, and proportion of health-related quality of life preservation. The Japan Clinical Oncology Group Protocol Review Committee approved this study protocol in April 2020. Ethics approval was granted by the National Cancer Center Hospital Certified Review Board. Patient enrollment began in August 2020. DISCUSSION: If the primary endpoint is met, short-course radiotherapy comprising 25 Gy in 5 fractions with concomitant and adjuvant temozolomide will be a standard of care for elderly patients with newly diagnosed glioblastoma. TRIAL REGISTRATION: Registry number: jRCTs031200099 . Date of Registration: 27/Aug/2020. Date of First Participant Enrollment: 4/Sep/2020.
Subject(s)
Antineoplastic Agents, Alkylating/therapeutic use , Brain Neoplasms/therapy , Glioblastoma/therapy , Temozolomide/therapeutic use , Aged , Antineoplastic Agents, Alkylating/administration & dosage , Brain Neoplasms/mortality , Brain Neoplasms/pathology , Combined Modality Therapy/methods , Dose Fractionation, Radiation , Drug Administration Schedule , Glioblastoma/mortality , Glioblastoma/pathology , Humans , Japan , Progression-Free Survival , Quality of Life , Temozolomide/administration & dosageABSTRACT
Immunotherapy has been shown to prolong survival in recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) in front-line use; however, subsequent systemic therapy has not been optimized. This study aimed to evaluate the safety and efficacy of cetuximab-containing chemotherapy after immunotherapy. We retrospectively analyzed patients with recurrent or metastatic SCCHN who underwent cetuximab-containing regimens after progression on immunotherapy. Of the 22 patients who met the inclusion criteria, 21 received paclitaxel and cetuximab, and 1 carboplatin and fluorouracil and cetuximab after immunotherapy. Nine patients achieved a partial response, 10 patients had stable disease as their best response on cetuximab-containing chemotherapy, yielding an overall response rate and disease control rate of 40.9 and 86.4%, respectively. The median progression-free survival was 5.2 months, and the median overall survival was 14.5 months. Ten patients developed grade 3-4 adverse events, including neutropenia (31.8%), acneiform rash (9.1%), anemia (4.5%), hypertransaminasemia (4.5%) and stomatitis (4.5%). The most frequent cetuximab-related toxicities across all grades were skin reactions (77.3%), hypomagnesemia (40.9%), stomatitis (27.3%), paronychia (13.6%) and keratitis (4.5%). There was no treatment-related death. Taken together, cetuximab-containing chemotherapy was effective and feasible even after immunotherapy.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Head and Neck Neoplasms/drug therapy , Immune Checkpoint Inhibitors/therapeutic use , Squamous Cell Carcinoma of Head and Neck/drug therapy , Adult , Aged , Carboplatin/administration & dosage , Cetuximab/administration & dosage , Cisplatin/administration & dosage , Female , Fluorouracil/administration & dosage , Follow-Up Studies , Head and Neck Neoplasms/immunology , Head and Neck Neoplasms/pathology , Humans , Male , Middle Aged , Paclitaxel/administration & dosage , Prognosis , Retrospective Studies , Squamous Cell Carcinoma of Head and Neck/immunology , Squamous Cell Carcinoma of Head and Neck/pathology , Survival RateABSTRACT
OBJECTIVE: To evaluate the safety and efficacy of hypofractionated whole breast irradiation for Asian women after breast-conserving surgery. This is an updated report with 5-year follow-up. METHODS AND MATERIALS: Asian women who had invasive breast cancer with clinical tumor size ≤3 cm, pN0-1c and negative inked margins were enrolled. Hypofractionated whole breast irradiation of 42.56 Gy/16 fractions was delivered, and boost irradiation of 10.64 Gy/4 fractions was added when the surgical margin was ≤5 mm. The primary endpoint was the proportion of grade ≥ 2 late adverse reactions within 3 years. Secondary endpoints included early adverse events, overall survival, disease-free survival, ipsilateral breast relapse-free survival, late adverse reactions and cosmetic outcome. Toxicities were evaluated using CTCAE ver3.0. Cosmetic outcomes were assessed using a 4-point scale and CTCAE ver3.0 for hyper/hypopigmentation, breast nipple/areolar deformity and breast volume/deformity. RESULTS: Between February 2010 and August 2012, 312 patients were enrolled, and 306 received hypofractionated whole breast irradiation. Median follow-up was 70.5 (range 7.6-88.9) months. The proportion of grade ≥ 2 late adverse reactions within 3 years was 4.3% (90% confidence interval 2.5-6.7%). Grade 2 early adverse events occurred in 38 (12.4%); none had grade 3/4. Five-year overall survival, disease-free survival and ipsilateral breast relapse-free survival were 98.7, 95.4 and 98.0%, respectively. Of the 304 evaluable patients, 29 (9.5%; 95% confidence interval 6.5-13.4%) had grade 2/3 late adverse reactions; none had grade 4/5. At 5 years, 70/289 (24.2%) showed any worsening of breast cosmetic changes. CONCLUSIONS: Hypofractionated whole breast irradiation is considered a standard treatment for Asian women with margin-negative invasive breast cancer after breast-conserving surgery.
Subject(s)
Breast Neoplasms/radiotherapy , Breast Neoplasms/surgery , Dose Fractionation, Radiation , Mastectomy, Segmental , Adult , Aged , Breast Neoplasms/mortality , Breast Neoplasms/pathology , Combined Modality Therapy/adverse effects , Combined Modality Therapy/methods , Disease-Free Survival , Female , Follow-Up Studies , Humans , Japan/epidemiology , Mastectomy, Segmental/adverse effects , Middle Aged , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/prevention & control , Neoplasm Staging , Radiotherapy, Adjuvant/adverse effects , Radiotherapy, Adjuvant/methods , Radiotherapy, Conformal/adverse effects , Radiotherapy, Conformal/methods , Treatment OutcomeABSTRACT
PURPOSE: Skin collimation provides a sharp penumbra for electron beams, while the effect of bremsstrahlung from shielding materials is a concern. This phantom study was conducted to evaluate the safety and efficacy of a real-time variable shape rubber containing-tungsten (STR) that can be placed on a patient's skin. METHODS: Electron beam profiles were acquired with the STR placed on a water-equivalent phantom and low melting-point alloy (LMA) placed at the applicator according to commonly used procedures (field sizes: 20- and 40-mm diameters). Depth and lateral dose profiles for 6- and 12-MeV electron beams were obtained by Monte Carlo (MC) simulations and were benchmarked against film measurements. The width of the off-axis distance between 80% and 20% doses (P80-20 ) and the maximum dose were obtained from the lateral dose profiles. Bremsstrahlung emission was analyzed by MC simulations at the depth of maximum dose (R100 ). RESULTS: The depth dose profiles calculated by the MC simulations were consistently within 2% of the measurements. The P80-20 at R100 for 20- and 40-mm diameters were 4.0 mm vs. 7.6 mm (STR vs. LMA) and 4.5 mm vs. 9.2 mm, respectively, for the 6-MeV electron beam with 7.0-mm-thick STR, and 2.7 mm vs. 5.6 mm and 4.5 mm vs. 7.1 mm, respectively, for the 12-MeV electron beam with 12.0-mm-thick STR. A hotspot was not observed on the lateral dose profiles obtained with the STR at R100 . The bremsstrahlung emission under the region shielded by the STR was comparable to that obtained with the LMA, even though the STR was placed on the surface of the phantom. CONCLUSIONS: Skin collimator with STR provided superior dosimetric characteristics and comparable bremsstrahlung emission to LMA collimator at the applicator. STR could be a new tool for the safe and efficient delivery of electron radiotherapy.
Subject(s)
Rubber , Tungsten , Electrons , Humans , Monte Carlo Method , Phantoms, Imaging , Radiometry , Radiotherapy Dosage , Radiotherapy Planning, Computer-AssistedABSTRACT
PURPOSE: The purpose of this study was to compare the dose-volume parameters and regression scatter plots of the iteratively improved RapidPlan (RP) models, specific knowledge-based planning (KBP) models, in volumetric-modulated arc therapy (VMAT) for prostate cancer over three periods. METHODS: A RP1 model was created from 47 clinical intensity-modulated radiation therapy (IMRT)/VMAT plans. A RP2 model was created to exceed dosimetric goals which set as the mean values +1SD of the dose-volume parameters of RP1 (50 consecutive new clinical VMAT plans). A RP3 model was created with more strict dose constraints for organs at risks (OARs) than RP1 and RP2 models (50 consecutive anew clinical VMAT plans). Each RP model was validated against 30 validation plans (RP1, RP2, and RP3) that were not used for model configuration, and the dose-volume parameters were compared. The Cook's distances of regression scatterplots of each model were also evaluated. RESULTS: Significant differences (p < 0.05) between RP1 and RP2 were found in Dmean (101.5% vs. 101.9%), homogeneity index (3.90 vs. 4.44), 95% isodose conformity index (1.22 vs. 1.20) for the target, V40Gy (47.3% vs. 45.7%), V60Gy (27.9% vs. 27.1%), V70Gy (16.4% vs. 15.2%), and V78Gy (0.4% vs. 0.2%) for the rectal wall, and V40Gy (43.8% vs. 41.8%) and V70Gy (21.3% vs. 20.5%) for the bladder wall, whereas only V70Gy (15.2% vs. 15.8%) of the rectal wall differed significantly between RP2 and RP3. The proportions of cases with a Cook's distance of <1.0 (RP1, RP2, and RP3 models) were 55%, 78%, and 84% for the rectal wall, and 77%, 68%, and 76% for the bladder wall, respectively. CONCLUSIONS: The iteratively improved RP models, reflecting the clear dosimetric goals based on the RP feedback (dose-volume parameters) and more strict dose constraints for the OARs, generated superior dose-volume parameters and the regression scatterplots in the model converged. This approach could be used to standardize the inverse planning strategies.
Subject(s)
Prostatic Neoplasms , Radiotherapy, Intensity-Modulated , Humans , Male , Organs at Risk , Prostatic Neoplasms/radiotherapy , Radiotherapy Dosage , Radiotherapy Planning, Computer-AssistedABSTRACT
BACKGROUND: The role of intensity-modulated radiation therapy in the treatment of cervical esophageal cancer remains unclear. The outcome of concurrent chemoradiotherapy for cervical esophageal squamous cell carcinoma using intensity-modulated radiation therapy was retrospectively evaluated. METHODS: Between 2004 and 2017, 36 patients with cervical esophageal cancer treated with intensity-modulated radiation therapy were included. Among these patients, one had stage II disease, three stage III, 19 stage IVA, and 13 stage IVB. All patients received radiotherapy at a dose of 60 Gy and concurrent platinum-based doublet chemotherapy. RESULTS: The median follow-up period for surviving patients was 36 months. Three-year locoregional control, progression-free survival, and overall survival rates were 54, 40, and 46%, respectively. Disease progression was noted in 20 out of 36 patients (56%). Grade 3 late toxicities were observed in four patients (three esophageal stenoses and one carotid artery stenosis). There were no grade 4-5 toxicities. Univariate analysis identified the duration of radiotherapy as a prognostic factor for overall survival. CONCLUSIONS: Chemoradiotherapy using intensity-modulated radiation therapy for locally advanced cervical esophageal carcinoma achieved satisfactory locoregional control and survival with acceptable toxicities.
Subject(s)
Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Radiotherapy, Intensity-Modulated , Chemoradiotherapy/adverse effects , Esophageal Neoplasms/drug therapy , Esophageal Neoplasms/radiotherapy , Esophageal Squamous Cell Carcinoma/drug therapy , Esophageal Squamous Cell Carcinoma/radiotherapy , Humans , Radiotherapy, Intensity-Modulated/adverse effects , Retrospective StudiesABSTRACT
BACKGROUND: A phase II study of adaptive two-step intensity-modulated radiotherapy (IMRT) with chemotherapy for nasopharyngeal cancer (NPC) (JCOG1015) was conducted to evaluate the efficacy and safety. METHODS: Patients aged 20-75 years with stages II-IVB NPC were enrolled. As adaptive two-step IMRT, computed tomography planning was performed twice before IMRT for the initial plan of 46 Gy/23 fractions and during treatment for the boost plan of 24 Gy/12 fractions with a total dose of 70 Gy. Chemotherapy (cisplatin 80 mg/m2/3-weeks × 3 courses) was administered concurrently with IMRT, followed by adjuvant chemotherapy (cisplatin at 70 mg/m2 with 5-FU 700 at mg/m2 for 5 days/4 weeks × 3 courses). RESULTS: Between 2011 and 2014, 75 patients were enrolled from 12 institutions. The 3-year overall survival (OS) for the 75 patients was 88%, and the upper and lower limits of the 95% CI of 78%-94% were higher than the expected 3-year OS of 75% for the target population adjusted by the actual proportion of stage II:III:IV = 21%:44%:35%. The 3-year progression-free survival (PFS) and loco-regional PFS were 71% [59-80%] and 77% [66-85%], respectively. Although no grade 4-5 late toxicities were observed, 15 patients (20%) developed grade 3 late toxicities. Grade 2 xerostomia was noted in 26%, 12%, and 9% at 1, 2, and 3 years after starting IMRT, respectively. CONCLUSIONS: Adaptive two-step IMRT for NPC demonstrated an excellent 3-year OS with acceptable toxicities. This method may be one treatment option for locally advanced NPC.
Subject(s)
Nasopharyngeal Neoplasms/drug therapy , Nasopharyngeal Neoplasms/radiotherapy , Radiotherapy, Intensity-Modulated/methods , Adult , Aged , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/therapeutic use , Chemotherapy, Adjuvant , Cisplatin/administration & dosage , Cisplatin/therapeutic use , Dose Fractionation, Radiation , Female , Humans , Male , Middle Aged , Nasopharyngeal Neoplasms/mortality , Nasopharyngeal Neoplasms/pathology , Radiation Injuries/etiology , Radiotherapy, Intensity-Modulated/adverse effects , Survival Analysis , Treatment Outcome , Xerostomia/etiologyABSTRACT
This study aimed to evaluate the possibility of reducing the imaging dose for image-guided radiotherapy by using planar kilovoltage orthogonal imaging and fiducial markers (kV-FM). We tested kilovoltage planar images under clinical imaging conditions for the pelvis (75 kVp, 200 mA, 50 ms) at a decreasing tube current (from 200 to 10 mA). Imaging doses were measured with a semiconductor detector. The visibility of the kV-FM, aspects of image quality (spatial resolution, low contrast resolution), and the resultant image registration reproducibility were evaluated using various shapes (folded, linear, tadpole-like) of fiducial markers containing 0.5% iron [Gold Anchor™ (GA); Naslund Medical AB, Huddinge, Sweden]. The GA phantom was created by placing these variously shaped GAs in an agar phantom. The imaging doses with 200 and 10 mA were approximately 0.74 and 0.04 mGy and they were correlated to the tube current (R2 = 0.999). Regardless of the marker's shape, the GA phantom ensured visibility even when the tube current was reduced to the minimum value (10 mA). The low contrast resolution was gradually decreased at less than 50 mA, but the spatial resolution did not change. Although the auto-registration function could not be used, manual-registration could be achieved with an accuracy of within 1 mm, even when the imaging dose was reduced to 1/20 of the clinical imaging condition for the pelvis. When using the GA as the fiducial marker, the imaging dose could be reduced to 1/20 of that used clinically while maintaining the accuracy of manual-registration using the kV-FM for image-guided radiotherapy of the pelvis.
Subject(s)
Fiducial Markers , Radiotherapy, Image-Guided , Drug Tapering , Gold , Humans , Phantoms, Imaging , Reproducibility of Results , SwedenABSTRACT
A single-arm multi-center confirmatory trial was started in Japan to confirm the efficacy and safety of post-radical hysterectomy concurrent chemoradiotherapy using intensity-modulated radiation therapy (IMRT-CCRT) for patients with high-risk uterine cervical cancer, for which the current standard treatment is CCRT using three-dimensional conformal radiation therapy (3DCRT-CCRT). This study began in April 2017 and a total of 220 patients will be accrued from 44 institutions within 3.5 years. The primary endpoint is 3-year relapse-free survival. The secondary endpoints are overall survival, loco-regional relapse-free survival, proportion of late lower gastrointestinal adverse events greater than or equal to grade 3, proportion of lower edema limbs, adverse events, and serious adverse events. This trial was registered at the Japan Registry of Clinical Trials as jRCTs031180194 (https://jrct.niph.go.jp/).
Subject(s)
Chemoradiotherapy/adverse effects , Radiotherapy, Intensity-Modulated/adverse effects , Uterine Cervical Neoplasms/therapy , Adult , Aged , Female , Humans , Hysterectomy , Japan , Middle Aged , Postoperative Period , Radiotherapy, Conformal/adverse effects , Uterine Cervical Neoplasms/surgery , Young AdultABSTRACT
OBJECTIVE: To evaluate the safety of hypofractionated whole breast irradiation in Japanese women after breast-conserving surgery. METHODS: Japanese women who had invasive breast cancer with a clinical tumor size ≤3 cm, pN0-1c and a negative inked margin were enrolled. Hypofractionated whole breast irradiation (42.56 Gy/16 fractions) was delivered, adding boost irradiation (10.64 Gy/4 fractions) when the surgical margin was ≤5 mm. The treatment course was meant to be completed within 29 days or 33 days (plus boost irradiation). The primary endpoint was the proportion of grade ≥2 of pre-specified late adverse reactions, including telangiectasia, ulceration, fibrosis, fracture, pneumonitis, cardiac ischemia/infarction, pericardial effusion and breast pain, within 3 years. A sample size of 310 patients was set, with one-sided alpha of 0.05, beta of 0.1, threshold value of 8% and expected value of 4%. Secondary endpoints included the proportion of treatment completion within the recommended period and early adverse events within 90 days. Adverse events/adverse reactions were evaluated using CTCAE-3.0. RESULTS: Between 2010 and 2012, 312 women were enrolled; 306 received hypofractionated whole breast irradiation, but 6 chose conventional fractionated WBI, with 301 patients (96.5%) treated within the recommended period. Grade 2 early adverse events were found in 38 patients (12.4%); none had grade 3/4. Among the 303 evaluable patients, 13 (4.3%; 90% CI 2.6-6.7) had grade 2/3 late adverse reactions, including one with grade 3 pneumonitis, which was under the threshold value. CONCLUSION: Hypofractionated whole breast irradiation is considered to be safe and one of the standard treatments for Japanese women with margin-negative invasive breast cancer after breast-conserving surgery.
Subject(s)
Breast Neoplasms/radiotherapy , Breast Neoplasms/surgery , Adult , Aged , Breast Neoplasms/pathology , Dose Fractionation, Radiation , Female , Follow-Up Studies , Humans , Japan , Middle Aged , Neoplasm Staging , Prospective Studies , Young AdultABSTRACT
Stereotactic body radiation therapy (SBRT) can yield excellent local tumor control, as well as survival benefit comparable to that of surgery for early-stage lung cancer. However, in terms of toxicity, SBRT might lead to fatal radiation pneumonitis. Lung diseases, such as chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD), are major risk factors for lung cancer. However, these patients are typically not candidates for the gold-standard treatment option, lobectomy, because of the perioperative risks. In addition, patients with poor respiratory function can be excluded in prospective clinical trials. Thus, SBRT for patients with pulmonary diseases is still challenging, but there appears to be a clinical role for this modality as an alternative treatment. However, there are few well-documented review articles on SBRT for patients with pulmonary diseases. Therefore, we aimed to review SBRT in the context of important patient-related factors, including COPD and ILD. SBRT is an acceptable alternative treatment option for patients with lung cancer who also have COPD with an equivalent risk of radiation pneumonitis to normal lung. However, latent ILD should be detected prior to treatment. The indication for SBRT should be decided by carefully considering the risks and benefit for patients with ILD.