Papers by Takeshi Kodaira
Japanese Journal of Clinical Oncology, Apr 5, 2022
It was not until around 2000 that human papillomavirus-related oropharyngeal carcinoma was recogn... more It was not until around 2000 that human papillomavirus-related oropharyngeal carcinoma was recognized as carcinoma with clinical presentations different from nonrelated head and neck carcinoma. Twenty years after and with the revision of the tumor–node–metastasis classification in 2017, various clinical trials focused on human papillomavirus-related oropharyngeal carcinoma to improve the prognosis and quality of life of patients with this disease. However, the incidence of human papillomavirus-related cancers is increasing, which is expected to be particularly prominent in Japan, where human papillomavirus vaccination is not widely available. In this review, we describe the current status of clinical trials (mainly focused on initial surgery and radiation dose reduction) for, primary and secondary prevention of, and the present status of human papillomavirus-related oropharyngeal carcinoma in Japan.
Japanese Journal of Clinical Oncology, Dec 9, 2020
Induction chemotherapy for LA-HNSCC chemotherapy for head and neck squamous cell carcinoma, based... more Induction chemotherapy for LA-HNSCC chemotherapy for head and neck squamous cell carcinoma, based on the evidence produced to date, and discusses the future prospects for this treatment.
Auris Nasus Larynx, Jul 1, 2023
Journal of Clinical Oncology, Jun 1, 2023
12104 Background: Cisplatin-induced acute kidney injury (C-AKI) is a common reason for treatment ... more 12104 Background: Cisplatin-induced acute kidney injury (C-AKI) is a common reason for treatment interruption in head and neck cancer patients who receive chemoradiotherapy (CRT). We developed a risk prediction model for C-AKI in patients from a randomized phase II/III trial of JCOG1008, which demonstrated that CRT with weekly cisplatin at 40 mg/m2 (weekly arm) was noninferior to 3-weekly cisplatin at 100 mg/m2 (3-weekly arm) in terms of overall survival for postoperative high-risk head and neck cancer ( J Clin Oncol 2022; 40: 1980-90). Methods: Two hundred fifty-one patients received RT with a total of 66 Gy/33 fr concurrently with 3-weekly or weekly cisplatin. AKI was defined using the AKI Network classification/staging system as an increase in serum creatinine of ≥0.3 mg/dL or a 1.5-fold or greater increase from baseline (≥ stage I) by 30 days after the completion of CRT. AKI risk prediction models were developed by combining explanatory variables which were expected to contribute, including age, sex, ECOG performance status, primary site, pathological stage, diabetes mellites, hypertension, main nutritional method, treatment arm, serum albumin, serum magnesium, and creatinine clearance (CCr) at registration. A logistic regression model with the Akaike information criterion was used to explore the optimal model. Results: Ninety-four of 251 (37.5%) patients developed C-AKI in this study. The optimal C-AKI risk prediction model was composed of four factors, including a primary site (hypopharynx/larynx or oral cavity/oropharynx, odds ratio [OR] 1.92 [95% CI, 1.10 to 3.30]), treatment arm (3-weekly arm or weekly arm, OR 1.75 [95% CI, 1.02 to 3.00]), serum albumin (≤ 3.5 g/dL or > 3.5 g/dL, OR 2.06 [95% CI, 1.11 to 3.87]) and CCr ( < 90 mL/min or ≥ 90 mL/min, OR 1.85 [95% CI, 1.05 to 3.26]). The incidence of C-AKI increased in accordance with a total count of the four factors (Table): with a total count of 0-1, 2 and 3-4, the incidence of clinically relevant stage II/III C-AKI was 2.9%, 11.5%, and 22.6%, respectively. When total count was ≤1, the positive and negative predictive values for stage II/III C-AKI development were 16.1% and 97.0%, respectively. Conclusions: We developed a risk prediction model for C-AKI in head and neck cancer patients who receive CRT using primary site, cisplatin administration method, serum albumin, and CCr. The high negative predictive value of this prediction model may help rule out the development of moderate to severe C-AKI. Clinical trial information: jRCTs031180135 . [Table: see text]
Journal of Clinical Oncology, Jun 1, 2023
6079 Background: A randomized phase II/III trial of JCOG1008 demonstrated that chemoradiotherapy ... more 6079 Background: A randomized phase II/III trial of JCOG1008 demonstrated that chemoradiotherapy (CRT) with weekly cisplatin at 40 mg/m2 (Weekly arm) was noninferior to 3-weekly cisplatin at 100 mg/m2 (3-weekly arm) in terms of overall survival (OS) for postoperative high-risk head and neck cancer (hazard ratio [HR], 0.69 [99.1% CI, 0.37 to 1.27 < 1.32]; J Clin Oncol 2022; 40: 1980-90). Acute kidney injury (AKI) is a major dose-limiting toxicity of cisplatin. Here, we investigated the impact of AKI on OS in patients treated with CRT in JCOG1008. Methods: A total of 251 patients who were treated with CRT in JCOG1008 were analyzed. AKI was defined as an increase in serum creatinine of ≥0.3 mg/dL or a 1.5-fold or more increase from baseline (≥stage I) within 30 days after completion of CRT, based on the AKI Network classification/staging system. OS in the two arms was compared by the development of AKI using the log-rank test. Results: The total incidence of AKI in the weekly arm was lower than that in the 3-weekly arm (38 of 122 [31.1%] vs. 56 of 129 [43.4%]). The incidence of stage II/III AKI was also lower in the weekly arm (8 of 122 [6.6%] vs. 19 of 129 [14.7%]). Total cisplatin dose was similar in patients who did and did not develop AKI in the weekly arm, but was lower in patients who developed AKI in the 3-weekly arm (Table). Moreover, no difference in OS was observed between patients who did and did not develop AKI in the weekly arm (HR, 1.06 [95% CI, 0.53 to 2.10]), whereas patients who developed AKI in the 3-weekly arm had poorer OS than those who did not (HR, 1.83 [95% CI, 1.04 to 3.21]). Conclusions: In this supplementary analysis of JCOG1008, development of AKI impacted OS in the 3-weekly arm, but not in the weekly arm. Consistent exposure to cisplatin through weekly fractionated administration appears of greater clinical significance than cumulative dose, providing maintenance of treatment intensity and better kidney safety, and likely also improving outcomes. Clinical trial information: jRCTs031180135 . [Table: see text]
BJR|Open
Objective: To clarify the peripheral dose changes, especially in the eye lens and thyroid gland r... more Objective: To clarify the peripheral dose changes, especially in the eye lens and thyroid gland regions, using an acrylic-lead shield in cone-beam computed tomography (CBCT). Methods: The acrylic-lead shield consists of system walls and a system mat. The radiophotoluminescence glass dosemeter was set on the eye lens and thyroid gland regions on the RANDO phantom. The system mat was laid under the RANDO phantom ranging from the top of the head to the shoulders, and then, the system walls shielded the phantom’s head. Additionally, the phantom was covered anteriorly with a band that had the same shielding ability as the system mat to cover the thyroid gland region. Protocols for CBCT imaging of the thoracic or pelvic region in clinical practice were used. The measurement was performed with and without the acrylic-lead shield. Results: The dose to the eye lens region was reduced by 45% using the system wall. Conversely, the dose to the thyroid gland was unchanged. The use of the system ...
Radiation Oncology
Background This study aimed to investigate preoperative spirometry and BMI as early predictors of... more Background This study aimed to investigate preoperative spirometry and BMI as early predictors of the mean heart and lung dose (MHD, MLD) in deep inspiration breath-hold (DIBH) radiotherapy. Methods Left-sided breast cancer patients underwent breast-conserving surgery followed by DIBH radiotherapy enrolled. Patients who were not available for preoperative spirometry were excluded. One hundred eligible patients were performed free-breathing (FB-) CT and DIBH-CT for plan comparison. We completed the correlative and multivariate analysis to develop the linear regression models for dose prediction. The residuals were calculated to explore the unpreferable subgroups and compare the prediction accuracy. Results Among the parameters, vital capacity (VC) and BMI showed the strongest negative correlation with MHD (r = − 0.33) and MLD (r = − 0.34), respectively. They were also significant in multivariate analysis (P < 0.001). Elderly and less VC were independent predictors of increasing ab...
International Journal of Radiation Oncology Biology Physics, 2012
Japanese Journal of Clinical Oncology, 2022
Salivary gland malignancies are rare neoplasms that have a broad histological spectrum and a vari... more Salivary gland malignancies are rare neoplasms that have a broad histological spectrum and a variety of biologic behaviors. Salivary gland malignancies are known as chemo-resistant tumors, which render optimal treatment challenging. This review summarizes the role of systemic therapy for salivary gland malignancies. To date, the advantage of adding concurrent chemotherapy has remained undefined for both postoperative and inoperable locally advanced salivary gland malignancy patients undergoing radiotherapy. For recurrent/metastatic disease, local and/or systemic treatment options should be discussed in a multidisciplinary setting with consideration to both patient needs and tumor factors. For symptomatic patients or those who may compromise organ function, palliative systemic therapy can be a reasonable option based on the results of phase II studies. Platinum combination regimens as first-line therapy have been widely accepted. Personalized therapies have become established options...
International Journal of Radiation Oncology*Biology*Physics, 2020
Pain relief is a major concern in the radiation therapy for symptomatic bone metastases. There ar... more Pain relief is a major concern in the radiation therapy for symptomatic bone metastases. There are previous studies about investigating the association between pain relief and clinical features. Materials/Methods: This retrospective study enrolled a total of 40 patients with painful spine metastasis who received palliative radiation therapy from 2018 to 2019. Exclusion criteria were: (1) NRS 0-1; (2) reirradiation; (3) treated with SBRT; (4) metal artifacts close to target spine and (5) other extraspinal metastases apart from target spine in radiation field. Pain response defined by international consensus criteria. The 5 clinical predictive factors referred from previous study included NRS, primary tumor sites, performance status (PS), and added biologically effective dose (BED10) in this analysis. As for radiomic features, 321 features were extracted from three specified models by CT scans, which was categorizes as spinal canal model (SC model), spine model (S model), spine and surrounding tissues model (SS model), respectively. Recursive Feature Elimination and the importance score which provided by random forest method were applied to features for feature selection. A random forest model was designed to use the six selected features. The predictive performance of Random Forest models built on six radiomic features was compared with two other models, such as clinical features model, and a combined model with three clinical and three radiomic features. Internal validation was performed using 'leave-one-out' cross-validation method. Area under the curve (AUC) was used as predictive performance metrics. Results: Overall 29 patients (72.5%) showed a response. The three radiomic features were extracted from SS (MajorAxisLength, Run-LengthNonUniformity). The random forest models built on clinical features, radiomic features, and combination features achieved AUC of 0.47 (95%-CI 0.27-0.68), 0.70 (95%-CI 0.51-0.88), 0.77(95%-CI 0.60-0.93). Conclusion: We evaluate our CT-based radiomic model for prediction of response in palliative radiation therapy to spinal metastasis, and found that the combination features model seemed to be useful compared to other models.
Cancer Management and Research, 2021
Durvalumab (anti-programmed cell death ligand-1) administration after concurrent chemoradiotherap... more Durvalumab (anti-programmed cell death ligand-1) administration after concurrent chemoradiotherapy (cCRT) has improved the survival of patients with unresectable, locally advanced (LA) stage III non-small cell lung cancer (NSCLC). Some patients are unable to complete cCRT and cannot receive immunotherapy due to poor performance status based on adverse events after cCRT. Immunotherapy plays an important role in anti-programmed cell death ligand-1 (PD-L1)-positive advanced NSCLC and is replacing chemotherapy. In addition, radiotherapy and immunotherapy have been reported to have a synergistic effect. This Phase II, multicenter study (DOLPHIN, WJOG11619L, JapicCTI-194840) is designed to assess the efficacy and safety of durvalumab plus concurrent curative radiation therapy for PD-L1-positive unresectable LA-NSCLC without chemotherapy. Unresectable LA stage III NSCLC patients aged 20 years or older with a World Health Organization/Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 and PD-L1 positivity are enrolled. The patients will receive curative radiation therapy (60 Gy) plus durvalumab 10 mg/kg every 2 weeks (q2w) for up to 12 months until there is evidence of disease progression (PD) or unacceptable toxicity. The primary endpoint is the 12-month progression-free survival rate as assessed by an independent central review. The secondary endpoints are progression-free survival, overall survival, objective response rate, treatment completion rate, and safety. Recruitment began in September 2019.
Journal of Radiation Research, 2021
The present study aimed to reduce the parotid gland dose in the hippocampus avoidance with whole-... more The present study aimed to reduce the parotid gland dose in the hippocampus avoidance with whole-brain radiotherapy (HA-WBRT) using the helical tomotherapy (HT). Ten patients who had previously undergone WBRT were randomly selected and enrolled in this study. During the treatment planning, two different techniques to the jaw were applied for each patient, namely, 1.0 cm fixed jaw and 2.5 cm dynamic jaw. To efficiently reduce the dose in the bilateral parotid glands, directional block (DB) mode was set. The DB is a function of a treatment planning system for the dose reduction in organs at risk. The standard HA-WBRT plan which did not reduce the parotid gland dose was also designed to compare the plan quality. Compared with the standard HA-WBRT plan, the parotid gland dose could be reduced by approximately 70% without extending the delivery time by adding the parotid gland on the DB mode to the dose constraint. In addition, the differences in dosimetric parameters observed between th...
Scientific Reports, 2021
This study aimed to develop a poly-ε-caprolactone (PCL) material that has a low melting point whi... more This study aimed to develop a poly-ε-caprolactone (PCL) material that has a low melting point while maintaining the deformation ability. The new PCL (abbreviated as 4b45/2b20) was fabricated by mixing two types of PCL with different molecular weights, numbers of branches, and physical properties. To investigate the melting point, crystallization temperature, elastic modulus, and elongation at break for 4b45/2b20 and three commercially available masks, differential scanning calorimetry and tensile tests were performed. The melting point of 4b45/2b20 was 46.0 °C, and that of the commercially available masks was approximately 56.0 °C (55.7 °C–56.5 °C). The elastic modulus at 60 °C of 4b45/2b20 was significantly lower than the commercially available masks (1.1 ± 0.3 MPa and 46.3 ± 5.4 MPa, p = 0.0357). In addition, the elongation at break of 4b45/2b20 were significantly larger than the commercially available masks (275.2 ± 25.0% and 216.0 ± 15.2%, p = 0.0347). The crystallization temper...
Japanese Journal of Clinical Oncology, 2020
Squamous cell carcinoma of the head and neck is characterized by an immunosuppressive environment... more Squamous cell carcinoma of the head and neck is characterized by an immunosuppressive environment and evades immune responses through multiple resistance mechanisms. A breakthrough in cancer immunotherapy employing immune checkpoint inhibitors has evolved into a number of clinical trials with antibodies against programmed cell death 1 (PD-1), its ligand PD-L1 and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) for patients with squamous cell carcinoma of the head and neck. CheckMate141 and KEYNOTE-048 were practice-changing randomized phase 3 trials for patients with platinum-refractory and platinum-sensitive recurrent or metastatic squamous cell carcinoma of the head and neck, respectively. Furthermore, many combination therapies using anti-CTLA-4 inhibitors, tyrosine kinase inhibitors and immune accelerators are currently under investigation. Thus, the treatment strategy of recurrent or metastatic squamous cell carcinoma of the head and neck is becoming more heterogeneous and...
International Journal of Radiation Oncology*Biology*Physics, 2019
To evaluate the safety and efficacy of thermotherapy combined radical radiotherapy concurrent che... more To evaluate the safety and efficacy of thermotherapy combined radical radiotherapy concurrent chemotherapy for Ib2, IIa and local advanced cervical cancer. Materials/Methods: 30 patients diagnosed with cervical cancer from Jan 1, 2016 to Dec 31, 2017 were retrospectively studied. Among the patients, 1 pathologic diagnosed adenocarcinoma and 29 of squamous cell carcinoma; FIGO stage Ib2 10 patients and IIa-IVa 20 patients. All patients underwent radical chemotherapy concurrent radiotherapy (CCRT). Radiation composed of pelvic external beam radiation (EBRT) (50.4Gy/1.8Gy/ 28f 5f/w, EQD2Z45Gy) and brachytherapy (6Gy/f 5f 2f/w, EQD2Z40Gy) concurrent chemotherapy of DDP 40mg/m 2 weekly, 6 weeks, total 55 days of treatment procedure. Hyperthermia (SR 1000 RF applicator, Xianke medical equipment co. LTD, Shenzhen ,China) were applied for these group of patients during the CCRT. Deep heating through the thermode to the tumor location 40.5～41 C 60 minutes twice a week, longer than 72hours interval. The temperature were read by the sensor which placed into the vagina. Objective response rate (ORR), time to progression (TTP) and side effects were analyzed. Results: 30 patients median age 53 years old (39-83y). Median follow up time was 16.5 months (9-28ms). Mean maximum tumor diameter of primary cervical cancer was 4.37AE0.28cm (2-8.3cm). ORR of end of EBRT before brachytherapy is 73% (CR+PR,22/30) and 4 patients CR; ORR of 1 months later after completion of CCRT is 96% (CR+PR,29/30) and 17 patients CR; ORR of 6 months later after completion of CCRT is 96% (CR+PR,29/30) and 20 patients CR. Mean local control time is 24.2AE1.54 months (95% Confidence Interval 21.2ms-27.3ms), Median TTP was 15 months (3-28ms), 1y and 2y local control rate was 83.3%. By the end of follow-up, 5 patients relapse in pelvic, 2 patients died because of distant metastasis. Early side effects of grade 1/2 myelosuppression was seen in 28 patients (93%), grade 4 myelosuppression was seen in 2 patients (7%). There were no grade 3/4 rectitis and grade 3/4 urethritis were observed. Conclusion: Thermotherapy Combined Radical CCRT for bulky Local Advanced Cervical Cancer is safe and effective and still need further investigation.
Radiotherapy and Oncology, 2019
Stereotactic radiosurgery for large brain metastases (BM) not amenable to surgical resection is a... more Stereotactic radiosurgery for large brain metastases (BM) not amenable to surgical resection is associated with limited local control and neurotoxicity, while hypofractionated stereotactic radiotherapy (HFSRT) has emerged as a promising option. We retrospectively evaluated 61 patients with BM larger than 2 cm in the maximum diameter, who were treated with HFSRT (mainly 35 Gy/5 fractions) in our center between 2006-2016, focusing on the effect of BM size on outcomes. Eligible patients were divided according to the maximum BM diameter (group A [23 patients]: ≥3 cm, group B [22 patients]: <3 cm) to assess the relationship between tumor size and prognosis or safety. The primary outcome was the local control rate (LCR), and secondary outcomes were the response rate (RR), brain progression-free survival (BPFS), median survival time (MST), and radionecrosis (RN). Univariate and multivariate analyses for LCR were conducted using Cox's proportional hazards model. In the 45 eligible patients (58 lesions) enrolled in this study, the RR was 86.4% with an overall LCR of 64.7% at 12 months (67.1% for group A and 61.5% for group B [p = 0.45]). The median BPFS and MST were 11.6 and 14.2 months, respectively. Univariate analyses revealed that female patients and gynecological cancer patients had poorer LCR, but they were not significantly independent prognostic factors (p = 0.06, 0.09, respectively). Two patients (4.4%) experienced RN that was detected more than 4 years after HFSRT. We conclude that HFSRT is safe for large BM but further studies are needed to determine optimal doses and fractions.
Japanese Journal of Clinical Oncology, 2019
A number of major modifications were made to the classification of head and neck carcinomas in th... more A number of major modifications were made to the classification of head and neck carcinomas in the eighth edition of the American Joint Committee on Cancer, Cancer Staging Manual and Union for International Cancer Control TNM classification of Malignant Tumors. These modifications were aimed at improving the prognosis prediction accuracy of the system. In this article, we review the new edition of the TNM classification system. Among the several changes in the new system, a separate algorithm for p16-positive oropharyngeal carcinoma was included, as were new chapters on ‘Head and Neck Skin Carcinoma’ and ‘Unknown Primary Carcinoma—Cervical Nodes.’ Changes to Tumor (T) classification were made by introducing the depth of invasion of oral carcinoma, whereas changes to Node (N) classification were made by adding extra-nodal extension. It is believed that these changes will help improve the accuracy of the system in the prediction of prognosis. However, it is necessary to verify their v...
Journal of Clinical Oncology, 2014
7558 Background: Concurrent chemoradiation therapy (CRT) is the current standard of care for pati... more 7558 Background: Concurrent chemoradiation therapy (CRT) is the current standard of care for patients with locally advanced lung adenocarcinoma, however little has been reported about the impact of EGFR mutation to CRT efficacy. Methods: From 2005-2012, we retrospectively screened 73 unresectable stage III adenocarcinoma patients who were examined EGFR mutation status and received definitive concurrent CRT consisting of platinum doublet in first-line setting, and compared the clinical outcomes and recurrence patterns according to mutation status. Results: Among 73 patients, EGFR mutation was detected in 21 (28.8%). Overall response rate did not differ between EGFR-mutant and wild-type patients (66.7% vs. 74.0%, p=0.362). Median recurrence-free survival (RFS) in concurrent CRT was significantly shorter in EGFR-mutated patients than wild-type patients (8.7 [95%CI: 6.7-10.8] vs. 13.5 [95%CI: 11.0-18.3] months, p=0.022). The 2 year recurrence-free survival rate was 5.6% and 23.8% in EGFR-mutant and wild-type ...
The British Journal of Radiology, 2001
An applicator enabling simultaneous intraluminal radiotherapy and intraluminal hyperthermia deliv... more An applicator enabling simultaneous intraluminal radiotherapy and intraluminal hyperthermia delivery was developed to improve the treatment results for locally advanced oesophageal carcinoma. Eight inoperable cases were treated by this method. Six cases received 40 Gy external irradiation followed by simultaneous intraluminal hyperthermia and radiotherapy (3 Gy and 4 Gy in three cases each) once weekly for 3 weeks; the remaining two cases received 50 Gy external irradiation followed by simultaneous intraluminal hyperthermia and radiotherapy (4 Gy) once weekly for 2 weeks. Hyperthermia was delivered by a radiofrequency current thermotherapy instrument for 30 min at an output that raised the oesophageal mucosal surface temperature to 42-43 degrees C. Intraluminal radiotherapy was delivered with a microSelectron to a submucosal depth of 5 mm after the first 15 min of hyperthermia. Four cases achieved complete response, with all demonstrating local control. Partial response was obtained in four cases, and three of these patients died of local recurrence. There were no significant adverse side effects apart from fistula in one case. In conclusion, simultaneous intraluminal radiotherapy and hyperthermia may improve the current treatment results for locally advanced oesophageal carcinoma.
International Journal of Radiation Oncology*Biology*Physics, 2016
Purpose/Objective(s): Intensity Modulated Radiation Therapy (IMRT) is increasingly used to spare ... more Purpose/Objective(s): Intensity Modulated Radiation Therapy (IMRT) is increasingly used to spare organs at risk in definitive treatment of anal cancer, however, treatment continues to result in significant hematologic toxicity. In a cooperative trial assessing IMRT (RTOG 0529), the rate of grade 2+ and grade 3+ hematologic toxicity was 73% and 58% respectively. During IMRT planning, sparing of the bone marrow compartment is often sacrificed in favor of small bowel sparing or PTV coverage. The mean bone marrow dose can predict for grade 3+ hematologic toxicity. Intensity Modulated Proton Therapy (IMPT) may reduce acute toxicity by decreasing the integral bone marrow dose and dose to other organs at risk (OARs). Materials/Methods: CT datasets of 9 patients with anal cancer previously treated with IMRT, VMAT, or 3DCRT at our institution were used for comparison. Both VMAT and IMPT plans were created for each patient. The IMPT plans were created using a Multi-Field Optimized (MFO), splittarget technique. Planning constraints for RTOG 0529 as well as bone marrow (mean <22 Gy, V10 <90%, and V40 <37%) were used for treatment planning. The dose to OARs including the bone marrow, bladder, small bowel, large bowel, femoral heads, and genitalia were compared with a paired t-test. Results: IMPT provided similar PTV coverage as VMAT plans (99% vs 98%, P Z 0.0381). The mean bone marrow dose with IMPT and VMAT plans was 17.42 Gy and 30.76 Gy respectively (P<0.0001). Based on the NTCP modeling for bone marrow toxicity IMPT should reduce the rate of grade III or higher hematologic events from 40% to <5%. IMPT also showed significant sparing of other organs at risk including the small and large bowel, femoral heads, and genitalia. Mean results of the OARs are included in Table 1 below. Conclusion: Dosimetric sparing of the bone marrow and other OARs using IMPT may reduce hematologic toxicity and improve acute tolerance of therapy. Reduction in acute toxicity should reduce treatment breaks, and in return potentially improve local control. Prospective studies assessing proton therapy for anal cancer are ongoing and in development to evaluate these potential improvements in acute toxicity.
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Papers by Takeshi Kodaira