Incidence and risk factors associated with the development of hypothyroidism after postoperative chemoradiotherapy for head and neck cancer patients with high-risk features: Supplementary analysis of JCOG1008.

BACKGROUND AND PURPOSE: Hypothyroidism is a recognized late adverse event following radiotherapy for head and neck cancer (HNC). In the JCOG1008 trial, we treated patients with high-risk HNC with postoperative chemoradiotherapy. We aimed to elucidate factors associated with hypothyroidism by analyzing the JCOG1008 data. MATERIALS AND METHODS: In 2012-2018, 261 patients from 28 institutions were enrolled in JCOG1008. Thyroid function tests were conducted to assess hypothyroidism, including free thyroxine (FT4) and thyroid-stimulating hormone assays. Hypothyroidism was defined as Grade 2 or higher in CTCAE v4.0. Various clinical and dosimetric parameters were analyzed. In radiotherapy, there were no dose constraints for the thyroid. Multivariable analysis was conducted on these variables to identify predictive factors for hypothyroidism. RESULTS: The analysis included 162 patients (57 with 3D-CRT and 105 with IMRT), with a median follow-up of 4.7 years (0.3-9.3 years). Among these, 27 (16.7 %) developed hypothyroidism within 2 years after radiotherapy. In a multivariable analysis, the weekly cisplatin [OR=7.700 (CI: 1.632-36.343, p = 0.010)] and baseline FT4 [OR=0.009 (CI: <0.001-0.313, p = 0.010)] were significantly associated with hypothyroidism in the IMRT group. Regarding dosimetric characteristics, V60Gy [OR=1.069 (CI: 0.999-1.143, p = 0.054)] was potentially associated with the development of hypothyroidism. CONCLUSION: The study revealed that the incidence of hypothyroidism within 2 years after postoperative chemoradiotherapy for high-risk HNC was 16.7 % based on analytical results from prospective clinical trials.

Stereotactic body radiation therapy for multiple lung cancers in a patient with six primary cancers: a case report.

BACKGROUND: Surgery is the standard care for patients with early-stage lung cancer, and stereotactic body radiation therapy is an option for those who are medically inoperable or refuse surgery. Medical developments in diagnostic and therapeutic strategies would prolong prognosis of patients with cancer. The number of patients with multiple cancers has also increased. Duplex primary malignant neoplasms are the most common, and triple or more primary malignant neoplasms were extremely rare. This is the first case of sextuple primary malignant neoplasms with lung cancer. CASE PRESENTATION: We report a case of two courses of stereotactic body radiation therapy for an 88-year-old Japanese male patient with six primary cancers in five organs. Cancers were detected in the thyroid, prostate, esophagus, bladder, and lungs. He also had a history of angina pectoris and had undergone percutaneous coronary intervention. Although he was capable of undergoing surgery for lung cancers, he refused it because he had experienced many invasive treatments, such as surgeries and percutaneous coronary intervention. In January 2020, the first stereotactic body radiation therapy was performed for the adenocarcinoma in the right lung. In March 2022, the second stereotactic body radiation therapy was performed for the nodule of the left lung. Although he complained of mild dyspnea after the first stereotactic body radiation therapy, we did not use steroids because his peripheral oxygen saturation was within the normal range. He had pleural effusion, cardiac dilatation, and pericardial effusion 2 months after the second stereotactic body radiation therapy, which improved with the use of compression stockings. CONCLUSION: A total of 43 and 17 months have passed since the first and second stereotactic body radiation therapy, respectively, there is no local recurrence and the patient can walk independently. We safely performed stereotactic body radiation therapy twice for our older patient with metachronous early-stage lung cancers. If another new tumor is detected, stereotactic body radiation therapy would be a good treatment option for the functional preservation of organs.

Cone-beam computed tomography-guided online adaptive radiotherapy for pharyngeal cancer with whole neck irradiation: dose-volume histogram analysis between adapted and scheduled plans.

The present study aimed to evaluate whether an adapted plan with Ethos™ could be used for pharyngeal cancer. Ten patients with pharyngeal cancer who underwent chemoradiotherapy with available daily cone-beam computed tomography (CBCT) data were included. Simulated treatments were generated on the Ethos™ treatment emulator using CBCTs every four to five fractions for two plans: adapted and scheduled. The simulated treatments were divided into three groups: early (first-second week), middle (third-fourth week), and late (fifth-seventh week) periods. Dose-volume histogram parameters were compared for each period between the adapted and scheduled plans in terms of the planning target volume (PTV) (D98%, D95%, D50% and D2%), spinal cord (Dmax and D1cc), brainstem (Dmax) and ipsilateral and contralateral parotid glands (Dmedian and Dmean). The PTV D98%, D95% and D2% of the adapted plan were significantly higher than those of the scheduled plans in all periods, except for D98% in the late period. The adapted plan significantly reduced the spinal cord Dmax and D1cc compared with the scheduled plan in all periods. Ipsilateral and contralateral parotid glands Dmean of the adapted plan were lower than those of scheduled plan in the late period. In conclusion, the present study revealed that the adapted plans could maintain PTV coverage while reducing the doses to organs at risk in each period compared with scheduled plans.

A phase III randomized controlled trial comparing local field with additional prophylactic irradiation in chemoradiotherapy for clinical-T1bN0M0 esophageal cancer: ARMADILLO trial (JCOG1904).

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).

Clinical outcomes and failure patterns after postoperative radiotherapy for oral cavity squamous cell carcinoma.

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 60 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 ≤ 56 Gy to the primary site than those receiving > 56 Gy (p = 0.016 and p = 0.032, respectively). CONCLUSION: PORT was effective for postoperative recurrences as well as for initially diagnosed oral cavity cancer. Doses greater than 56 Gy to the primary site may be required in PORT for OSCC.

Dose difference between anisotropic analytical algorithm (AAA) and Acuros XB (AXB) caused by target's air content for volumetric modulated arc therapy of head and neck cancer.

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.

Clinical course of longer than five years after definitive radiotherapy for nasopharyngeal carcinoma.

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.

Evaluation of In-room Volumetric Imaging Doses for Image-guided Radiotherapy: A Multi-institutional Study.

Aims: We investigated imaging dose and noise under clinical scan conditions at multiple institutions using a simple and unified method, and demonstrated the need for diagnostic reference levels in image-guided radiotherapy (IGRT). Materials and Methods: Nine cone-beam and helical computed tomography (CT) scanners (Varian, Elekta, Accuray Inc., and BrainLAB) from seven institutions were investigated in this study. The weighted cone-beam dose index (CBDIw) was calculated for head and pelvic protocols using a 100 mm pencil chamber under the conditions used in actual clinical practice at each institution. Cone-beam CT image noise was evaluated using polymethylmethacrylate head and body phantoms with diameters of 16 and 32 cm, respectively. Results: For head and pelvic protocols, CBDIw values ranged from 0.94-6.59 and 1.47-20.9 mGy, respectively. Similarly, standard deviation (SD) values ranged from 9.3-34.0 and 26.9-97.4 HU, respectively. The SD values tended to increase with decreasing imaging dose (r = -0.33 and -0.61 for the head and pelvic protocols, respectively). Conclusions: Among the nine machines, the imaging dose for high imaging dose institutions was approximately 20 mGy to the pelvic phantom, and there was a 14-fold difference in dose compared with the other institutions. These results suggest the need to establish DRLs for IGRT to guide clinical decision-making.

Long-Term Follow-up of a Randomized Controlled Trial on Accelerated Radiation Therapy Versus Standard Fractionated Radiation Therapy for Early Glottic Cancer (JCOG0701A3).

PURPOSE: We previously reported the primary results of JCOG0701, a randomized, multicenter, phase 3, noninferiority trial comparing accelerated fractionation (Ax) to standard fractionation (SF) for early glottic cancer. In the primary results, although the similar efficacy of 3-year progression-free survival and toxicity of Ax compared with SF was observed, the noninferiority of Ax was not confirmed statistically. To evaluate the long-term follow-up results of JCOG0701, we conducted JCOG0701A3 as an ancillary study of JCOG0701. METHODS AND MATERIALS: In JCOG0701, 370 patients were randomly assigned to receive SF of 66 to 70 Gy (33-35 fractions; n = 184) or Ax of 60 to 64.8 Gy (25-27 fractions; n = 186). The data cutoff date for this analysis was in June 2020. Overall survival, progression-free survival, and late adverse events including central nervous system ischemia were analyzed. RESULTS: With a median follow-up period of 7.1 years (range, 0.1-12.4), progression-free survival of the SF and Ax arms were 76.2% and 78.2% at 5 years and 72.7% and 74.8% at 7 years (P = .44). OS of the SF and Ax arms were 92.7% and 89.6% at 5 years and 90.8% and 86.5% at 7 years (P = .92). Among 366 patients with a protocol treatment, the cumulative incidence of late adverse events of the SF and Ax arms were 11.9% and 7.4% at 8 years (hazard ratio, 0.53; 95% CI, 0.28-1.01; P = .06). Central nervous system ischemia of grade 2 or higher was observed in 4.1% for the SF arm and 1.1% for the Ax arm (P = .098). CONCLUSIONS: After long-term follow-up, Ax showed comparable efficacy to SF and a tendency for better safety. Ax may be suitable for early glottic cancer because of its convenience in minimizing treatment time, cost, and labor.

Comparison of the Characteristics of Two Types of Parallel-plate Ionization Chamber Under Small-field Electron Irradiation.

BACKGROUND/AIM: This study compared two types of parallel-plate ionization chamber to clarify the pitfalls of dosimetry in electron radiation therapy. MATERIALS AND METHODS: The ion recombination correction factor and polarity effect correction factor, sensitivity, and percentage depth doses (PDDs) of PPC05 and PPC40 parallel-plate ionization chambers were compared in a small-field electron beam. The output ratios were measured for 4-20 MeV electron beams with field sizes of 10 cm × 10 cm, 6 cm × 6 cm, and 4 cm × 4 cm. Furthermore, the films were placed in water and positioned in the beam with their surface perpendicular to the beam axis, and lateral profiles were obtained for each beam energy and each field. RESULTS: Regarding PDDs, at depths greater than the peak dose, the percentage depth dose for PPC40 was smaller than that for PPC05 in small fields and at beam energies greater than 12 MeV, which could be attributed to the lack of lateral electron equilibrium at small depths and multiple scattering events at large depths. The output ratio of PPC40 was approximately 0.025-0.038, which was lower than that of PPC05 in a 4 cm × 4 cm field. For large fields, the lateral profiles were similar, regardless of the beam energy, however, for small fields, the flatness of the lateral profile was beam energy dependent. CONCLUSION: The PPC05 chamber, which has a smaller ionization volume, is therefore more suitable than the PPC40 chamber for small-field electron dosimetry, in particular at high beam energies.

Impact of rectal gas on the planning target volume margin for pelvic bone and prostate matching in prostate cancer patients receiving volumetric-modulated arc therapy.

We performed daily cone-beam computed tomography (CBCT) to determine the impact of rectal gas on the movements of prostate and seminal vesicles (SVs). We aimed to determine the relationship between planning target volume (PTV) margins and rectal gas. In 30 treatments of 15 prostate cancer patients, excessive rectal gas was removed and CBCT images were analyzed. Image registration between planning CT and daily CBCT images before and after rectal gas removal was performed for pelvic bone and prostate matching. The couch movement distance between each matching was considered the prostate movement. In addition, we measured SV tip movement between each matching. The anterior-posterior movement of the prostate before rectal gas removal (3.1 ± 2.9 mm) was significantly greater than that after rectal gas removal (1.2 ± 1.2 mm; p < 0.01). The left-right and superior-inferior movements were similar regardless of the presence or absence of rectal gas. The SV movement distances before and after rectal gas removal were 11.0 ± 5.8 mm and 4.6 ± 3.8 mm, respectively (p < 0.01), in pelvic bone matching, and 8.0 ± 4.2 mm and 3.8 ± 3.2 mm, respectively (p < 0.01), in prostate matching. After rectal gas removal, the SV position did not differ significantly between each matching. In 26 of the 30 treatments, SV movement distance in the presence of rectal gas was >6 mm, which is the minimum PTV margin at our institution. In comparison, after rectal gas removal and prostate matching, only 6 treatments demonstrated an SV movement distance of >6 mm. In the presence of rectal gas, the SVs require greater PTV margins than the prostate. Rectal gas removal should be considered if the movement distance on prostate matching is greater than the minimum PTV margin at treating institution.

Volumetric Modulated Arc Therapy Planning for Craniospinal Irradiation With a New O-ring Linac.

This study aims to determine the feasibility of using a new O-ring linear accelerator (Halcyon, Varian Medical Systems, CA, USA) to perform treatment planning using volumetric modulated arc therapy (VMAT) for craniospinal irradiation (CSI). A 20-year-old male patient with leukemia was selected. The planning target volume (PTV) was contoured to include the entire contents of the brain and spinal canal. The PTV margin was 10 mm applied to the clinical target volume (CTV). VMAT (RapidArc, Varian Medical Systems, CA, USA) planning was performed using four isocenter with five arcs, two full rotation arcs to cover the brain and upper part of the spinal cord, and one full rotation arc for the lower part of the spinal cord. The plan was created using the auto-feathering photon optimizer calculation of the planning system. The conformity index (CI) and heterogeneity index (HI) as well as dose-volume histograms of organs at risk (OAR) were evaluated. The patient position of ±3.0 mm in the craniocaudal direction was moved in to simulate the effect of treatment inaccuracy. The total treatment time was also measured. The CI and HI were 1.09 and 8.44, respectively. The mean dose (PTV) was 105.5%, and the mean dose (OARs) was lower than the planning dose constraints. Simulations with a patient position shift of ±3.0 mm resulted in an error of less than ±10.0% of the planned dose to the spinal cord. The total treatment time was within 15 minutes. VMAT planning for CSI with Halcyon achieved high conformality, uniform dose distribution, low dose to the surrounding normal tissues, and reduced treatment time.

The development and characterization of an all-purpose bolus for radiotherapy.

Objective.The purpose of this study was to develop a new bolus (HM bolus), with tissue equivalence, transparency, reusability, and free shaping at approximately 40 °C for excellent adhesion, and to evaluate the feasibility of clinically using this bolus as an ideal bolus.Approach.We summarized the advantages and disadvantages of existing boluses. To evaluate dose characteristics, a vinyl gel sheet bolus (Gel bolus) and HM bolus placed on a water-equivalent phantom were used to obtain the percentage depth dose (PDD) of electron (6 MeV, 9 MeV) and photon (4 MV, 6 MV) beams. The average dose difference of the HM bolus and Gel bolus was calculated. The Gel bolus, a soft rubber bolus (SR bolus), and HM bolus were placed in adherence to a pelvic phantom. CT images taken after shaping and 1, 2, and 3 weeks after shaping were used to evaluate the adhesion and reproducibility using air gap and dice similarity coefficient (DSC).Main results.The average dose difference for electron beams was 0.16% ± 0.79% and photon beams was 0.06% ± 0.34%, both within 1% of the PDD results. The HM bolus showed the same build-up effect and dose characteristics as the Gel bolus. The mean air gap values for the Gel bolus, SR bolus, and HM bolus were 96.02 ± 43.77 cm3, 34.93 ± 21.44 cm3, and 4.40 ± 1.50 cm3, respectively. The mean DSC values compared to initial images for the Gel bolus, SR bolus, and HM bolus were 0.363 ± 0.035, 0.556 ± 0.042, and 0.837 ± 0.018, respectively. Excellent adhesion was observed in the CT simulation and during the treatment period.Significance.The HM bolus has unique features, such as tissue equivalence, transparency, reusability, and free shaping for excellent adhesion, and is thus an ideal bolus for use in clinical cases.

Plan quality association between dummy run and individual case review in a prospective multi-institutional clinical trial of postoperative cervical cancer patients treated with intensity-modulated radiotherapy: Japan clinical Oncology Group study (JCOG1402).

BACKGROUND AND PURPOSE: The Japan Clinical Oncology Group (JCOG) 1402 conducted a multicenter clinical trial of postoperative intensity-modulated radiotherapy (IMRT) for high-risk uterine cervical cancer patients. We assess effectiveness of the quality assurance (QA) program in central review through dummy runs (DRs) performed before patient enrollment and post-treatment individual case review (ICR), and clarify the pitfalls in treatment planning. MATERIAL AND METHODS: The ICRs were conducted using the same QA program as the DR for 214 plans. The deviations were compared with those demonstrated in the DRs, and the pitfalls were clarified. Fifteen face-to-face meetings were held with physicians at participating institutions to provide feedback. RESULTS: Two-hundred and eighty-eight deviations and nine violations were detected in the 214 plans. The patterns of the deviations observed in the ICRs were similar to that in the DR. Frequent deviations were observed in clinical target volume (CTV) delineations, 50% in the DRs and 37% in the ICRs, respectively. In the ICRs, approximately 1.4 deviations/violations were observed per plan, which was lower than DR. Nine violations included inaccurate CTV delineation and improper PTV (planning target volume) margin, which had risks in loco-regional failures by inadequate dose coverage. CONCLUSIONS: Our developed QA program commonly used in DR and ICR clarified the pitfalls in treatment plans. Although the frequent deviations in CTV delineations were observed in the ICR, the deviations decreased compared to that in the DR. More specified face-to-face meetings with participating institutions will be necessary to maintain the quality of IMRT in the clinical protocol.

Visualization of tumor hypoxia and re-oxygenation after stereotactic body radiation therapy in early peripheral lung cancer: A prospective study.

BACKGROUND AND PURPOSE: In this study, fluoromisonidazole positron emission tomography (F-MISO PET/CT) was used to evaluate tumor hypoxia and re-oxygenation in patients with lung tumors treated with stereotactic body radiation therapy (SBRT). MATERIALS AND METHODS: Patients with T1-2 N0 lung cancer were included in this study. The prescribed dose was 48-52 Gy in four fractions. F-MISO PET/CT was performed twice, before SBRT and 1-3 days after the first irradiation. The maximum standardized uptake value (SUVmax) and tumor/muscle ratio (TMR) were evaluated as indicators of hypoxia. The threshold for hypoxia was defined as a TMR of 1.30 or more. RESULTS: Between 2016 and 2021, 15 patients were included. Pre-treatment tumor hypoxia was observed in nine tumors (60 %). TMR in all six tumors without pre-treatment hypoxia rose after single high-dose irradiation. In contrast, TMR in six of nine tumors with pre-treatment hypoxia dropped after irradiation, suggesting re-oxygenation. Although no local recurrence was noted, regional and/or distant relapses were seen in four patients (27 %). Of these, three had tumors with abnormal F-MISO uptake. The remaining patient had a tumor without signs of hypoxia on pre-treatment PET/CT. The 2-year progression free survival of patients with tumors with and without pre-treatment hypoxia were 30 % and 63 %, respectively (p = 0.319). CONCLUSION: Tumor hypoxia reduced after single high-dose irradiation. Tumor with F-MISO uptake seems to be an unfavorable prognostic factor in lung SBRT.

Difference in failure patterns after stereotactic body radiotherapy for lung cancer according to clinical T stage based on 4D computed tomography.

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 (p = 0.001). No significant differences were observed in OS according to the clinical T stage (p = 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 (p = 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.

Double enhancement effect of a surface dose with tungsten rubber bolus in photon radiotherapy for keloids and superficial tumors.

To clarify the dosimetric characteristics of a real-time variable shape rubber-containing tungsten (STR) bolus in a clinical plan and investigate the efficacy of the STR bolus in photon radiotherapy for keloids and other superficial tumors. A 5 mm gel bolus or 1 mm STR bolus was placed on a solid water phantom. Tangential irradiation was performed using a TomoTherapy Radixact-X9 and 6 MV X-ray flattening-filter-free beam, and the surface dose was measured with radiochromic film. Clinical-like plans (TomoDirect; TD and TomoHelical; TH) were applied with the same geometry and the dose distributions were measured. The increase in surface dose by the build-up effect and backscatter was 37.7% and 8.0% for the gel bolus, and 40.5% and 26.4% for the STR bolus, respectively. In the TD and TH plans, the increase in surface dose was 27.4% and 48.3% for the gel bolus, and 39.0% and 63.2% for the STR bolus. Similary, changes in the sagittal plane dose were - 3.9% and 6.1% for the gel bolus, and - 6.3% and 6.9% for the STR bolus. The STR bolus effectively increased the surface dose by the build-up effect and backscatter in photon radiotherapy for keloids and other superficial tumors.

A phase II study of concurrent chemoradiotherapy with 5-fluorouracil and mitomycin-C for squamous cell carcinoma of the anal canal (the JROSG 10-2 trial).

This study assessed the efficacy of chemoradiotherapy for squamous cell carcinoma of the anal canal (SCCAC). Patients with T1-4N0-3M0 SCCAC received chemoradiotherapy with 5-fluorouracil (5-FU, 800 mg/m2/day, 96-h infusion) and mitomycin-C (MMC, 10 mg/m2 bolus). Patients treated with 3-dimensional conformal radiotherapy (3D-CRT) or intensity-modulated radiotherapy (IMRT) were administered 36.0 Gy in 20 fractions or 49.5 Gy in 33 fractions for elective nodal irradiation and 59.4 Gy in 33 fractions for primary tumor and metastatic nodal irradiation. The sample size was considered sufficient to estimate 95% confidence intervals (CIs) for the true 2-year disease-free survival (DFS) within a width of +15% when the expected true 2-year DFS was 70%. The primary endpoint was 2-year DFS. The secondary endpoints were 2-year overall survival (OS), locoregional control (LC), colostomy-free survival (CFS) and adverse events. Thirty-one patients were enrolled between January 2014 and July 2019. The median follow-up was 33.3 months (range, 16.2-65.8 months). Among the 31 patients, 13%, 32%, 16% and 39% had stage I, II, IIIA and IIIB disease, respectively. Thirty patients were treated with IMRT. Complete response (CR) was achieved in 27 patients. The 2-year DFS, OS, LC and CFS rates were 77.4% (95% CI, 58.4-88.5%), 93.5% (95% CI, 76.6-98.3%), 83.9% (95% CI, 65.5-92.9%) and 80.6% (95% CI, 61.9-90.8%), respectively. One patient experienced grade 3 late adverse events; however, no grade ≥ 4 late adverse events occurred. Good DFS with a low rate of late adverse events was observed. Chemoradiotherapy with 5-FU and MMC was effective for SCCAC.

Overcoming Problems Caused by Offset Distance of Multiple Targets in Single-isocenter Volumetric Modulated Arc Therapy Planning for Stereotactic Radiosurgery.

Purpose: The purpose of the study is to investigate the impact of large target offset distances on the dose distribution and gamma passing rate (GPR) in single-isocenter multiple-target stereotactic radiosurgery (SIMT SRS) using volumetric modulated arc therapy (VMAT) with a flattening filter-free (FFF) beam from a linear accelerator. Methods: Two targets with a diameter of 1 cm were offset by "±2, ±4, and ±6 cm from the isocenter in a verification phantom for head SRS (20 Gy/fr). The VMAT plans were created using collimator angles that ensured the two targets did not share a leaf pair from the multi-leaf collimator. To evaluate the low-dose spread intermediate dose spill (R50%), GPRs were measured with a criterion of 3%/2 mm using an electronic portal imaging device and evaluated using monitor unit (MU), modulation complexity score for VMAT (MCSv), and leaf travel (LT) parameters. Results: For offsets of 2, 4, and 6 cm, the respective parameters were: R50%, 4.75 ± 0.36, 5.13 ± 0.36, and 5.11 ± 0.33; GPR, 95.01%, 93.82%, and 90.67%; MU, 5893 ± 186, 5825 ± 286, and 5810 ± 396; MCSv, 0.24, 0.16, and 0.13; and LT, 189.21 ± 36.04, 327.69 ± 67.01, and 430.39 ± 114.34 mm. There was a spread in the low-dose region from offsets of ≥4 cm and the GPR negatively correlated with LT (r = -0.762). There was minimal correlation between GPR and MU or MCSv. Conclusions: In SIMT SRS VMAT plans with an FFF beam from a linear accelerator, target offsets of <4 cm from the isocenter can minimize the volume of the low-dose region receiving 10 Gy or more. During treatment planning, it is important to choose gantry, couch, and collimator angles that minimize LT and thereby improve the GPR.

New strategy of a lung compensating technique with STR for total body irradiation.

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.