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Objective To assess the feasibility of external beam radiotherapy without central shielding in definitive radiotherapy for Japanese patients with cervical cancer. Methods We retrospectively analysed the data of cervical cancer patients treated with definitive radiotherapy consisting of external beam radiotherapy without central shielding and three-dimensional-image-guided brachytherapy. Results The study included 167 patients (T1 + 2 = 108, T3 + 4 = 59) from eight Japanese institutions. For three-dimensional-image-guided brachytherapy, intra-cavitary and interstitial brachytherapy was utilized in 33 patients (20%). The median follow-up was 26.6 months (interquartile range, 20–43.2). The maximum rectal D2 (75 Gy)/bladder D2 (90 Gy) constraints were deviated by 6%/10% and 10%/5% for T1 + 2 and T3 + 4, respectively. The 2-year incidence of ≥grade 3 proctitis/cystitis was 4%/1% for T1 + 2 and 10%/2% for T3 + 4. The 2-year local progression-free survival was 89% for T1 + 2 and 82% for T3 + 4. For T1 + 2, the 2-year local progression-free survival for the high-risk clinical target volume D90 ≥ 68 Gy (indicated by receiver operating characteristic analysis; area under the curve = 0.711) was 92% versus 67% for Conclusions Definitive radiotherapy consisting of external beam radiotherapy without central shielding and three-dimensional-image-guided brachytherapy was feasible for Japanese patients with cervical cancer. Dose de-escalation from the current global standards is suggested for patients with T1 + 2 disease.

Background/Aim: The aim of this study was to evaluate the mechanical performance and the effect on dose distribution and deliverability of volumetric modulated arc therapy (VMAT) plans for prostate cancer created with the commercial knowledge-based planning (KBP) system (RapidPlan™). Materials and Methods: Three institutions, A, B, and C were enrolled in this study. Each institution established and trained a KBP model with their own cases. CT data and structures for 45 patients at institution B were utilized to validate the dose-volume parameters (D(2(%)), D(95(%),) and D(98(%)) for target, and V(50(%)), V(75(%),) and V(90(%)) for rectum and bladder), and the following mechanical performance parameters and gamma passing rates of each KBP model: leaf sequence variability (LSV), aperture area variability (AAV), total monitor unit (MU), modulation complexity score for VMAT (MCSv), MU/control point (CP), aperture area (AA)/CP, and MU×AA/CP. Results: Significant differences (p95% for all cases in each institution. Dose distribution and mechanical performance significantly differed between the three models. Conclusion: Each KBP model had different dose distributions and mechanical performance but could create an acceptable plan for deliverability regardless of mechanical performance.

Background/Aim: This study evaluated the calculation accuracy of the stopping power ratio (SPR) using dual-energy computed tomography with fast kilovoltage switching (FKSCT) for particle therapy. Materials and Methods: A tissue characterization phantom with various reference materials was scanned to obtain single-energy computed tomography (SECT) images and generate virtual monochromatic images at 77 keV (VMI(77keV)) and 140 keV (VMI(140keV)), water density (WD) images, and effective Z (Z(eff)) images. For SECT, VMI(77keV) and VMI(140keV) lookup tables were generated to convert the measured Hounsfield value into the theoretical SPR for a normal phantom size. Subsequently, the reference materials were scanned in small and large phantoms. The SPR was calculated using the lookup tables of SECT (SPR(SECT)) images, VMI(77keV) (SPR(77keV)), and VMI(140keV) (SPR(140keV)), and it was derived from the WD and Z(eff) (SPR(WD)). Results: In the normal-sized phantom, the overall mean difference between SPR(WD) and theoretical SPR was −0.3%, and remained below 2% for most reference materials. For the large phantom, the overall mean absolute difference for SPR(140keV) (3.0%, p=0.006) and SPR(WD) (3.2%, p=0.002) for the reference materials was significantly lower than that for SPR(SECT) (5.9%). For the small phantom, a significant reduction in the mean difference in the SPR calculation was observed in SPR(77keV) (1.0%, p=0.001) and SPR(140keV) (1.1%, p=0.013) compared with SPR(SECT) (2.2%). Conclusion: VMI(140keV) generated using FKSCT significantly improves the estimation accuracy of SPR compared with SECT. Thus, FKSCT may be used to improve the dose calculation accuracy for treatment planning of particle therapy.

Background/Aim: Dosimetric parameters in volumetric modulated arc therapy (VMAT), non-coplanar VMAT (NC-VMAT), and automated NC-VMAT (HyperArc, HA) were compared for patients with maxillary sinus carcinoma (MSC). Patients and Methods: Twenty HA plans were generated to deliver 70.4, 64, and 46 Gy for planning target volumes with high (PTV1), intermediate (PTV2), and low risk (PTV3), respectively. The VMAT and NC-VMAT plans were retrospectively generated using the same optimized parameters as those used in the HA plans. Results: For PTV1, the three treatment plans provided comparable target coverages. For PTV2, the D(95%), D(99%,) and D(min) in the HA plans (64.7±1.2, 62.7±2.1 and 54.6±6.2 Gy, respectively) were significantly higher (p

Whole-body magnetic resonance imaging (WB-MRI) is currently used worldwide for detecting bone metastases from prostate cancer. The 5-year survival rate for prostate cancer is > 95%. However, an increase in survival time may increase the incidence of bone metastasis. Therefore, detecting bone metastases is of great clinical interest. Bone metastases are commonly located in the spine, pelvis, shoulder, and distal femur. Bone metastases from prostate cancer are well-known representatives of osteoblastic metastases. However, other types of bone metastases, such as mixed or inter-trabecular type, have also been detected using MRI. MRI does not involve radiation exposure and has good sensitivity and specificity for detecting bone metastases. WB-MRI has undergone gradual developments since the last century, and in 2004, Takahara et al., developed diffusion-weighted Imaging (DWI) with background body signal suppression (DWIBS). Since then, WB-MRI, including DWI, has continued to play an important role in detecting bone metastases and monitoring therapeutic effects. An imaging protocol that allows complete examination within approximately 30 min has been established. This review focuses on WB-MRI standardization and the automatic calculation of tumor total diffusion volume (tDV) and mean apparent diffusion coefficient (ADC) value. In the future, artificial intelligence (AI) will enable shorter imaging times and easier automatic segmentation.

Dosimetric potential of knowledge-based RapidPlan planning model trained with HyperArc plans (Model-HA) for brain metastases has not been reported. We developed a Model-HA and compared its performance with that of clinical volumetric modulated arc therapy (VMAT) plans.From 67 clinical stereotactic radiosurgery (SRS) HyperArc plans for brain metastases, 47 plans were used to build and train a Model-HA. The other 20 clinical HyperArc plans were recalculated in RapidPlan system with Model-HA. The model performance was validated with the 20 plans by comparing dosimetric parameters for normal brain tissue between clinical plans and model-generated plans. The 20 clinical conventional VMAT-based SRS or stereotactic radiotherapy plans (CL-VMAT) were reoptimized with Model-HA (RP) and HyperArc system (HA), respectively. The dosimetric parameters were compared among three plans (CL-VMAT vs. RP vs. HA) in terms of planning target volume (PTV), normal brain excluding PTVs (Brain - PTV), brainstem, chiasm, and both optic nerves.In model validation, the optimization performance of Model-HA was comparable to that of HyperArc system. In comparison to CL-VMAT, there were no significant differences among three plans with respect to PTV coverage (p 0.17) and maximum dose for brainstem, chiasm, and optic nerves (p 0.40). RP provided significantly lower VThe Model-HA has the potential to significantly reduce the normal brain dose of the original VMAT plans for brain metastases.

Background/aim The aim of this retrospective study was to detect the frequency, reasons, and significant factors for not receiving immunotherapy after chemoradiotherapy in non-small cell lung cancer (NSCLC) patients. Patients and methods Thirty-four patients with NSCLC received definitive chemoradiotherapy. The endpoint of this study was receiving durvalumab within 45 days after chemoradiotherapy for NSCLC. Results Twenty-five of 34 (73%) patients received immunotherapy within 45 days after chemoradiotherapy. The reasons for not receiving immunotherapy were radiation pneumonitis (50%), radiation esophagitis (10%), and four other reasons (40%). Univariate analysis showed that significant factors for not receiving immunotherapy were elective nodal irradiation (ENI)+ and chronic obstructive pulmonary disease (COPD)+. The rate of immunotherapy was 100% (17/17 cases) in the COPD- and ENI- group, and 16% (1/6 cases) in the COPD+ and ENI+ group. Conclusion ENI for NSCLC complicated with COPD decreased the rate of immunotherapy after definitive chemoradiotherapy.

The prognosis of hepatocellular carcinoma (HCC) with portal vein tumour thrombus (PVTT) is poor. We conducted a prospective study to evaluate the efficacy and safety of tri-modality therapy, including preoperative stereotactic body radiotherapy (SBRT) and surgery, followed by hepatic arterial infusion chemotherapy (HAIC) in HCC patients with PVTT. In this report, we investigated the pathology of the irradiated PVTT specimen in resected cases and SBRT-related acute toxicity. A total of 8 HCC patients with PVTT received preoperative SBRT targeting the PVTT at a dose of 48 Gy in 4 fractions at our institute from 2012 to 2016. Of the eight patients, six underwent surgery, while the remaining two did not because of disease progression. At the pathological examination, all patients’ irradiated PVTT specimens showed necrotic tissue, and three of six patients showed complete pathological response. Two patients showed 30% necrosis with high degeneration and one patient, with 30% necrosis without degeneration, was the only recurrent case found during the follow-up period (median: 22.5, range: 5.9–49.6 months). No SBRT-related acute toxicity worse than grade 2 was observed from SBRT to surgery. In conclusion, the preoperative SBRT for HCC was pathologically effective and the acute toxicities were tolerable.

This study introduced an A-mode portable ultrasound bladder scanner, the Lilium® α-200 (here after Lilium; Lilium Otsuka, Kanagawa, Japan), for the treatment of prostate cancer patients with hypofractionated volumetric modulated arc therapy to improve the reproducibility of bladder volume (BV).Thirty patients were advised to maintain full BV prior to computed tomography (CT) simulation and daily treatment. Among these, the BV of 15 patients was measured using Lilium until a BV of 80% in the simulation was achieved (with the Lilium group). Daily cone-beam CT (CBCT) was performed for treatment. The correlation between BV measured by CBCT and Lilium was assessed. The differences in the BV and dosimetric parameters of the bladder in the CBCT versus planning CT were compared between the groups with and without Lilium.There was a significantly strong relationship (r = 0.796, p 0.05) between the BVs measured using CBCT and Lilium. The relative BV ratios to simulation CT 0.5 and 2 were observed in 10.3% and 12.7%, respectively, of treatment sessions without Lilium group, while these ratios were 1% and 2.8%, respectively, in the Lilium group. The mean absolute difference in the range of VThe use of the A-mode portable ultrasound bladder scanner significantly improved the reproducibility of the BV, resulting in few variations in the dosimetric parameters for the bladder.

Simple Summary Nasal cavity or paranasal sinus tumors are rare, with treatment outcomes reported as a small subgroup of all head and neck tumors. However, due to their unique anatomical characteristics (proximity to the optic pathway and skull base), treatment efficacy and toxicity in should be focused on those areas. After curative treatment involving radiotherapy, local recurrence is common and treated mainly through surgery. Unfortunately, surgery is difficult in almost all cases due to the critical organs involved. Systemic chemotherapy plays a central role in managing recurrent tumors; however, its efficacy is insufficient to extend longevity. Reirradiation is challenging, as it leads to higher toxicity, but it potentially offers long-lasting tumor control, including cure and symptom palliation in patients with no other remaining therapeutic options. We examined this subgroup using multi-institutional data and found that reirradiation is feasible for treating nasal cavity or paranasal sinus tumors. A relatively high distant metastasis ratio was found after reirradiation, especially in patients with lymph node metastasis. Abstract We evaluated the efficacy and toxicity of reirradiation of nasal cavity or paranasal sinus tumors. We collected and analyzed multi-institutional data of reirradiation cases. Seventy-eight patients with nasal or paranasal sinus tumors underwent reirradiation. The median survival time was 20 months with a medial follow-up of 10.7 months. The 2-year local control and overall survival rates were 43% and 44%, respectively. Tumor volume (≤25 cm3), duration between previous radiotherapy and reirradiation (≤12 months), histology (squamous cell carcinoma), male sex, and lymph node involvement were predisposing factors for poor survival. Distant metastasis was observed in 20 patients (25.6%). Grade ≥ 3 adverse events were observed in 22% of the patients, including five grade 4 (8.6%) cases and one grade 5 (1.2%) case. Tumor location adjacent to the optic pathway was a significant predisposing factor for grade ≥3 visual toxicity. Reirradiation of nasal and paranasal sinus tumors is feasible and effective. However, adverse events, including disease-related toxicities, were significant. Prognostic factors emerge from this study to guide multidisciplinary approaches and clinical trial designs.

Low-energy virtual monochromatic images (VMIs) derived from dual-energy computed tomography (DECT) systems improve lesion conspicuity of head and neck cancer over single-energy CT (SECT). However, DECT systems are installed in a limited number of facilities; thus, only a few facilities benefit from VMIs. In this work, we present a deep learning (DL) architecture suitable for generating pseudo low-energy VMIs of head and neck cancers for facilities that employ SECT imaging.We retrospectively analyzed 115 patients with head and neck cancers who underwent contrast enhanced DECT. VMIs at 70 and 50 keV were used as the input and ground truth (GT), respectively. We divided them into two datasets: for DL (104 patients) and for inference with SECT (11 patients). We compared four DL architectures: U-Net, DenseNet-based, and two ResNet-based models. Pseudo VMIs at 50 keV (pVMIU-Net produced the lowest MAE (13.32 ± 2.20 HU) and highest PSNR (47.03 ± 2.33 dB) and SSIM (0.9965 ± 0.0009), with statistically significant differences (P 0.001). The HU evaluation showed good agreement between the GT and U-Net. U-Net produced the smallest absolute HU difference for the tumor, at 5.0 HU.Quantitative comparisons of physical parameters demonstrated that the proposed U-Net could generate high accuracy pVMI

Purpose To evaluate the utility of the use of iterative cone-beam computed tomography (CBCT) for machine log file-based dose verification during volumetric modulated arc therapy (VMAT) for prostate cancer patients. Methods All CBCT acquisition data were used to reconstruct images with the Feldkamp-Davis-Kress algorithm (FDK-CBCT) and the novel iterative algorithm (iCBCT). The Hounsfield unit (HU)-electron density curves for CBCT images were created using the Advanced Electron Density Phantom. The I'mRT and anthropomorphic phantoms were irradiated with VMAT after CBCT registration. Subsequently, fourteen prostate cancer patients received VMAT after CBCT registration. Machine log files and both CBCT images were exported to the PerFRACTION software, and a 3D patient dose was reconstructed. Mean dose for planning target volume (PTV), the bladder, and rectum and the 3D gamma analysis were evaluated. Results For the phantom studies, the variation of HU values was observed at the central position surrounding the bones in FDK-CBCT. There were almost no changes in the difference of doses at the isocenter between measurement and reconstructed dose for planning CT (pCT), FDK-CBCT, and iCBCT. Mean dose differences of PTV, rectum, and bladder between iCBCT and pCT were approximately 2% lower than those between FDK-CBCT and pCT. For the clinical study, average gamma analysis for 2%/2 mm was 98.22% ± 1.07 and 98.81% ± 1.25% in FDK-CBCT and iCBCT, respectively. Conclusions A similar machine log file-based dose verification accuracy is obtained for FDK-CBCT and iCBCT during VMAT for prostate cancer patients.

BACKGROUND/AIM To assess the impact of the width of multileaf collimator (MLC) on dose distributions on HyperArc fractionated stereotactic irradiation for multiple (5-10) brain metastases. PATIENTS AND METHODS Twenty-one HyperArc (HA) plans were generated using the high definition (HD) MLC (2.5 mm) to deliver 30-35 Gy in 3-5 fractions (HA-HD). The HyperArc plans using Millennium (ML) MLC (5 mm) were retrospectively generated (HA-ML) using the same planning parameters with HA-HD. Dosimetric parameters between the planning target volume (PTV) and organs at risk (OARs) were compared. RESULTS The conformity index was significantly higher (p

Previous studies have reported conflicting results for the effect of overall treatment time with stereotactic body radiotherapy on tumor control in early-stage non-small-cell lung cancer. To examine this effect, we conducted a propensity score-weighted, retrospective, observational study at a single institution. We analyzed the data of 200 patients with early-stage non-small-cell lung cancer who underwent stereotactic body radiotherapy (48 Gy in 4 fractions) at our institution between January 2007 and October 2013. Patients were grouped into consecutive (overall treatment time = 4–5 days, n = 116) or non-consecutive treatment groups (overall treatment time = 6–10 days, n = 84). The outcomes of interest were local control and overall survival. The Cox regression model was used with propensity score and inverse probability of treatment weighting. The median overall treatment times in the consecutive and non-consecutive groups were 4 and 6 days, respectively. The 5-year local control and overall survival rates in the consecutive vs. the non-consecutive group were 86.3 vs. 77.2% and 55.5 vs. 51.8%, respectively. After propensity score weighting, consecutive stereotactic body radiotherapy was associated with positive local control (adjusted hazard ratio 0.30, 95% confidence interval 0.14–0.65; p = 0.002) and overall survival (adjusted hazard ratio 0.56, 95% confidence interval 0.34–0.91; p = 0.019) benefits. The prolonged overall treatment time of stereotactic body radiotherapy treatment negatively affected the outcomes of patients with early-stage non-small-cell lung cancer. To our knowledge, this is the first study to show that in patients with early-stage non-small-cell lung cancer treated with the same dose-fractionation regimen, consecutive stereotactic body radiotherapy has a more beneficial effect on tumor control than non-consecutive stereotactic body radiotherapy.

OBJECTIVE This is an ancillary study of a multi-institutional randomized non-inferiority phase III trial of accelerated fractionation (AF) versus standard fractionation (SF) radiation therapy for T1-2N0M0 glottic cancer (JCOG0701). Biopsy specimens of tumors from the patients enrolled in the JCOG0701 are collected and the association between clinical outcomes and histopathologic features such as expression of epithelial cell adhesion molecule (EpCAM), p53, and p16 were investigated. METHODS Five slices of undyed slides from biopsy specimens were sent to the National Cancer Center Hospital and all the specimens were assessed for the expression of EpCAM, p53, and p16. The primary objective was to investigate the association between 3-year progression-free survival (PFS) and expression of EpCAM, p53, and p16. RESULTS A total of 88 out of 370 patients were enrolled in this ancillary study. The 3-year PFS for tumors with strong expression of EpCAM was 70.6% (95% CI 43.1%-86.6%), while that of tumors without strong expression of EpCAM was 77.5% (95% CI 65.9%-85.5%) with no remarkable difference between groups (P = .67). Likewise, there was no significant difference in 3-year PFS between tumors regardless of p53 or p16 status. However, in a subgroup analysis for 17 patients with a strong expression of EpCAM, AF showed better 3-year PFS than SF (100% vs 54.5%, P = .07). CONCLUSIONS From the current study, it could not be concluded that EpCAM, p16, and p53 were prognostic factors for early-stage glottic cancer after primary radiation therapy. AF might be an appropriate fractionation for tumors with a strong expression of EpCAM. LEVEL OF EVIDENCE 3 Laryngoscope, 131:1522-1527, 2021.

BackgroundPrevious studies have reported conflicting results for the effect of overall treatment time (OTT) on tumor control with stereotactic body radiotherapy (SBRT) for early-stage non-small cell lung cancer (NSCLC). To examine this effect, we conducted a propensity score-weighted, retrospective, observational study at a single institution.MethodsWe analyzed the data of 200 patients with early-stage NSCLC who underwent SBRT (48 Gy in 4 fractions) at our institution between January 2007 and October 2013. Patients were grouped into consecutive (OTT = 4–5 days, n = 116) or non-consecutive treatment groups (OTT = 6–10 days, n = 84). The outcomes of interest were local control and overall survival. The Cox regression model was used with propensity score and inverse probability of treatment weighting.ResultsThe median OTTs in the consecutive and non-consecutive groups were 4 and 6 days, respectively. The 5-year local control and overall survival rates in the consecutive group vs. non-consecutive group were 86.3% vs. 77.2% and 55.5% vs. 51.8%, respectively. After propensity score-weighting, consecutive SBRT was associated with positive local control (adjusted hazard ratio 0.30, 95% confidence interval 0.14–0.65; p=0.002) and overall survival benefits (adjusted hazard ratio 0.56, 95% confidence interval 0.34–0.91; p=0.019). Conclusions Prolonged OTT negatively affected the outcomes of patients with early-stage NSCLC treated with SBRT. To our knowledge, this is the first study to show that in patients with early-stage NSCLC treated with the same dose-fractionation regimen, consecutive SBRT has a more beneficial effect on tumor control than does non-consecutive SBRT.

The incidence of hypopharyngeal and supraglottic cancer (HSC) is high in Japan. This study aimed to retrospectively identify risk factors for death unrelated to cancer and death from aspiration pneumonia after definitive radiotherapy (RT) for HSC.Overall, 391 patients who began definitive RT for HSC between 2006 and 2014 were identified from the Osaka International Cancer Institute electronic database. Among 391 patients, 33 had a history of surgery for esophageal cancer (EC) and 19 received simultaneous RT for synchronous EC. The cause of death was divided into 3 main categories: "cancer under study," "other malignancy," and "unrelated to cancer." Cox proportional hazard model was used to estimate the hazard ratio (HR).The median follow-up for survivors was 8 (range 3.6-14.1) years. At the last follow-up, 202 patients died. Death from "cancer under study," "other malignancy," and "unrelated to cancer" occurred in 92 (45.5%), 55 (27.2%), and 55 (27.2%) patients, respectively. Twelve patients died from aspiration pneumonia. In multivariate analysis for death unrelated to cancer and death from aspiration pneumonia, history of surgery for EC (HR: 3.87, p 0.001; HR: 6.84, p = 0.007, respectively) and simultaneous RT for synchronous EC (HR: 3.74, p = 0.006; HR: 16.37, p 0.001, respectively) were significant risk factors.The laryngeal preservation approach by RT for HSC patients with a history of surgery for EC and simultaneous RT for synchronous EC should be used with caution.

AIM To identify clinical benefits of dose escalation in accelerated hyperfractionated radiotherapy (AH-RT) for stage III non-small-cell lung cancer (NSCLC) using propensity score-matched (PSM) analysis. MATERIALS AND METHODS Our study retrospectively examined 294 patients undergoing definitive radiotherapy [131 patients, conventional once-daily radiotherapy (OD-RT); and 163, AH-RT] who were followed-up for a median of 40.4 months. The impact of overall survival (OS), progression-free survival (PFS), and locoregional control (LRC) was investigated. RESULTS Pre-PSM, the median OS, PFS, and LRC durations were 23.1 vs. 39.9 (p=0.03), 8.9 vs. 13.5 (p

We aimed to determine whether pretreatment metabolic tumor volume of the primary tumor (T-MTV) or T classification would be a better predictor of laryngectomy-free survival (LFS) and overall survival (OS) after chemoradiotherapy in patients with locally advanced laryngeal or hypopharyngeal cancer requiring total laryngectomy. We analyzed 85 patients using a Cox proportional hazards model and evaluated its usefulness by Akaike's information criterion. A T-MTV cut-off value was determined by time-dependent receiver operating characteristic curve analysis. Interobserver reliability for measuring T-MTV was estimated by the intraclass correlation coefficient (ICC). After adjustment for covariables, T-MTV, irrespective of whether a continuous or dichotomized variable, and T classification remained independent predictors of LFS and OS. Large T-MTV (>28.7 mL) was associated with inferior LFS (hazard ratio [HR], 4.16; 95% confidence interval [CI], 1.97-8.70; P = 0.0003) and inferior OS (HR, 3.18; 95% CI, 1.47-6.69; P = 0.004) compared with small T-MTV (≤28.7 mL). The T-MTV model outperformed the T classification model in predicting LFS and OS (P = 0.007 and 0.01, respectively). Three-year LFS and OS rates for patients with small versus large T-MTV were 68% vs 9% (P < 0.0001) and 77% vs 25% (P < 0.0001), respectively, whereas those for patients with T2-T3 versus T4a were 61% vs 31% (P = 0.003) and 71% vs 48% (P = 0.10), respectively. ICC was 0.99 (95% CI, 0.99-1.00). Given the excellent interobserver reliability, T-MTV is better than T classification to identify patients who would benefit from the larynx preservation approach.

Early laryngeal, especially glottic, cancer is a good candidate for radiotherapy because obvious early symptoms (e.g. hoarseness) make earlier treatment possible and with highly successful localized control. This type of cancer is also a good model for exploring the basic principles of radiation oncology and several key findings (e.g. dose, fractionation, field size, patient fixation, and overall treatment time) have been noted. For example, unintended poor outcomes have been reported during transition from 60Cobalt to linear accelerator installation in the 1960s, with usage of higher energy photons causing poor dose distribution. In addition, shell fixation made precise dose delivery possible, but simultaneously elevated toxicity if a larger treatment field was necessary. Of particular interest to the radiation therapy community was altered fractionation gain as a way to improve local tumor control and survival rate. Unfortunately, this interest ceased with advancements in chemotherapeutic agents because alternate fractionation could not improve outcomes in chemoradiotherapy settings. At present, no form of acceleration can potentially compensate fully for the lack of concurrent chemotherapy. In addition, the substantial workload associated with this technique made it difficult to add extra fractionation routinely in busy clinical hospitals. Hypofractionation, on the other hand, uses a larger single fractionation dose (2–3 Gy), making it a reasonable and attractive option for T1–T2 early glottic cancer because it can improve local control without the additional workload. Recently, Japan Clinical Oncology Group study 0701 reprised its role in early T1–T2 glottic cancer research, demonstrating that this strategy could be an optional standard therapy. Herein, we review radiotherapy history from 60Cobalt to modern linear accelerator, with special focus on the role of alternate fractionation.

The present study aimed to describe the clinical results of re-irradiation (Re-RT) for spine or pelvic bone metastasis at the same initial irradiated area. Between April 2010 and March 2014, cases involving 98 patients with spine or pelvic bone metastasis who had undergone Re-RT at five institutions were reviewed. The clinical outcomes following Re-RT were evaluated, including overall survival (OS) and severe adverse events. The median time interval from initial radiation therapy (RT) to Re-RT was 439 days (range, 23–4,993 days), and the median duration of patient follow-up was 256 days (range, 11–2,284 days). The median biological effective dose for the Re-RT was 150 Gy2 (range, 17–240 Gy2; α/β = 2). Severe late adverse events occurred in two patients who underwent three-dimensional conformal radiotherapy for lumbar spine or pelvic bone metastases, which may be associated with tumor progression. The median survival time following Re-RT was 255 days, and the actuarial OS rate at 1 year was 36%. The interval between initial RT and Re-RT, and their performance statuses (PS) were significant independent prognostic factors for OS rates in multivariate analysis. Re-RT for spine or pelvic bone metastases is a relatively acceptable option with low risk of anticipated severe adverse events, particularly for patients with good PS following a long disease-free interval.

Objectives The aim of this phase I study is to identify the maximum tolerated dose (MTD) and recommended dose (RD) of CPT-11 in combination with UFT/LV and radiation in patients with locally recurrent rectal cancer. Methods Patients with histologically proven rectal cancer with local recurrence were eligible for this study. Escalating doses of CPT-11 (30-60 mg/m2) were administered on days 3, 10, 24, and 31. UFT (300 mg/m2) and LV (75 mg/body) were given on days 1-5, 8-12, 22-26, and 29-33. Radiotherapy doses consisted of 50 Gy in daily fractions of 2.0 Gy each, 5 times per week, for total 5 weeks. Results We recruited 27 patients, and the MTD of CPT-11 was 60 mg/m2 due to the occurrence of dose-limiting toxicity of grade 3 diarrhea. Major grade 3 adverse events were neutropenia (5/27; 18.5%) and diarrhea (6/27; 22.2%). No grade 4 adverse event was observed throughout this treatment. Conclusions The combined chemoradiotherapy with oral UFT/LV plus CPT-11 is feasible and promising. The recommended dose for further phase II trials is determined to be 50 mg/m2 of CPT-11.

Preoperative chemoradiotherapy (CRT) with gemcitabine (GEM) for pancreatic cancer is often accompanied by vertebral compression fractures (VCFs). This study aimed to establish the incidence of VCFs and identify the related risk factors (RFs) to elucidate how to decrease the overall incidence of VCF.We investigated 220 patients with resectable or borderline-resectable pancreatic cancers who had completed preoperative CRT between 2006 and 2011. The RFs associated with VCF were analyzed in a total of 1308 thoracolumbar vertebral bodies.Thirty-seven VCFs occurred in 25 patients (11%); the cumulative incidence at two years was 18.9%. Univariate analysis revealed female sex, age and high daily GEM concentration during radiotherapy as RFs for VCF. The multivariate mixed effects logistic regression model demonstrated that the most responsible factor was radiation dose (p0.001). We estimated the radiation condition resulting in a fracture incidence of ⩽5% by counting the patient's number of the three RFs. For patients with three factors, the mean vertebral dose was 22.0 Gy.The RFs for VCF after CRT were identified. The side effect of VCF might be avoided by regulating the radiation dose to neighboring vertebral bodies after considering the RFs.