Robust treatment planning in scanned carbon-ion radiotherapy for pancreatic cancer: Clinical verification using in-room computed tomography images.

Purpose: Carbon-ion beam (C-beam) has a sharp dose distribution called the Bragg peak. Carbon-ion radiation therapy, such as stereotactic body radiotherapy in photon radiotherapy, can be completed in a short period by concentrating the radiation dose on the tumor while minimizing the dose to organs at-risk. However, the stopping position of C-beam is sensitive to density variations along the beam path and such variations can lower the tumor dose as well as cause the delivery of an unexpectedly high dose to the organs at risk. We evaluated the clinical efficacy of a robust planning technique considering gastrointestinal gas (G-gas) to deliver accurate radiation doses in carbon-ion radiotherapy for pancreatic cancer. Materials and methods: We focused on the computed tomography (CT) value replacement method. Replacement signifies the overwriting of CT values in the CT images. The most effective replacement method for robust treatment planning was determined by verifying the effects of the three replacement patterns. We selected 10 consecutive patients. Pattern 1 replaces the CT value of the G-gas contours with the value of the region without G-gas (P1). This condition indicates a no-gas state. Pattern 2 replaces each gastrointestinal contour using the mean CT value of each contour (P2). The effect of G-gas was included in the replacement value. Pattern 3 indicates no replacement (P3). We analyzed variations in the target coverage (TC) and homogeneity index (HI) from the initial plan using in-room CT images. We then performed correlation analysis on the variations in G-gas, TC, and HI to evaluate the robustness against G-gas. Results: Analysis of variations in TC and HI revealed a significant difference between P1 and P3 and between P2 and P3. Although no statistically significant difference was observed between P1 and P2, variations, including the median, tended to be fewer in P2. The correlation analyses for G-gas, TC, and HI showed that P2 was less likely to be affected by G-gas. Conclusion: For a treatment plan that is robust to G-gas, P2 mean replacement method should be used. This method does not necessitate any particular software or equipment, and is convenient to implement in clinical practice.

Clinical Outcomes of Scanning Carbon-ion Radiotherapy for Soft Tissue Sarcoma of the Extremities.

BACKGROUND/AIM: Carbon-ion radiotherapy (CIRT) has been reported to obtain favorable results in the treatment of bone and soft tissue malignancies; however, studies on CIRT for soft tissue sarcomas (STS) of the extremities are limited. Here, we have retrospectively evaluated the therapeutic efficacy and adverse events associated with scanning CIRT (sCIRT) for STS of the extremities at our institution. PATIENTS AND METHODS: Thirteen consecutive patients with STS who underwent sCIRT between January 2017 and January 2020 were included in the study. The total dose of sCIRT was set at 67.2-70.4 Gy (RBE), which was provided in 16 fractions. Overall survival (OS), progression-free survival (PFS), and local control (LC) were estimated using the Kaplan-Meier method. Toxicity was evaluated using Common Terminology Criteria for Adverse Events v5.0. RESULTS: The cohort consisted of 10 males and 3 females with a median age of 69 years (range=38-95 years). Median duration of observation was 31.8 months (range=7.4-56.4 months). Tumors were localized to the upper extremity in 2 cases and to the lower extremity in 11 cases. Median maximum tumor diameter was 11.7 cm (range=3.0-36.6 cm), while 3-year OS, PFS, and LC were 61.5%, 44.9%, and 79.1%, respectively. Acute toxicity of grade 3 or higher was not observed. Late toxicity included grade 3 peripheral nerve palsy and decreased range of motion in 1 and 1 patient each. Late toxicity of Grade 4 or higher was not observed. CONCLUSION: sCIRT for STS of the extremities demonstrates favorable therapeutic results with acceptable toxicity.

Evaluation of Safety for Scanning Carbon-Ion Radiotherapy in Hemodialysis Patients With Prostate Cancer.

Background/Aim The efficacy and safety of carbon-ion radiotherapy (CIRT) for prostate cancer have already been demonstrated. The number of hemodialysis (HD) patients is increasing. Although the toxicity of CIRT in HD patients may be more severe, it has been insufficiently investigated. Therefore, we retrospectively analyzed the safety of CIRT for HD patients with prostate cancer in the present study. Materials and methods Five HD patients with prostate cancer who underwent CIRT at the Kanagawa Cancer Center during November 2015-2020 were included in this study. CIRT was delivered by the raster scanning method (sCIRT). Adverse events were assessed using the Common Terminology Criteria for Adverse Events version 5.0. The dose-volume histogram (DVH) parameters of the target volume and normal organs were evaluated between initial planning computed tomography (CT) and in-room CT images. Results In the acute phase, Grade 1 genitourinary toxicity was recorded in one patient. In the late phase, Grade 1 genitourinary toxicity was recorded in two patients. No gastrointestinal toxicities were noted during the follow-up period. In-room CT analysis revealed no significant differences among all DVH parameters of the target volume and normal organs when compared with the treatment plan dose. Conclusions The safety of sCIRT for prostate cancer in HD patients was investigated in the present study. In-room CT analysis suggested the robustness of the treatment plan. According to the present results, sCIRT for prostate cancer can be safely performed in HD patients.

Three cases of retroperitoneal sarcoma in which bioabsorbable spacers (bioabsorbable polyglycolic acid spacers) were inserted prior to carbon ion radiotherapy.

From August 2019 to August 2020, we inserted polyglycolic acid (PGA) spacers and administered carbon ion radiotherapy (CIRT) to three cases of retroperitoneal sarcoma at our hospital. We aimed to investigate its utility and safety for retroperitoneal sarcoma. We analyzed changes in PGA spacer volume and corresponding computed tomography (CT) values in addition to the dose distribution using in-room CT images that were obtained during treatment. We assessed adverse events and investigated the suitability, safety and effectivity of PGA spacer insertion. During treatment, changes in PGA spacer volumes and CT values were confirmed. Volumes increased in patients with a folded PGA spacer, and it increased 1.6-fold by the end of irradiation compared with planning CT. The CT values decreased by 20-50 Hounsfield units at the end of irradiation compared to the planning CT. Dose distribution evaluation showed that the dose to the gastrointestinal tract adjacent to the tumor was maintained below the tolerable dose, and a sufficient dose was delivered to the target by PGA spacer insertion. One case of subileus caused during abdominal surgery for PGA spacer insertion occurred. No other adverse events, such as digestive disorders, were observed. CIRT with PGA spacer insertion for retroperitoneal sarcomas is safe and effective. For cases in which there is no option but to perform irradiation using a PGA spacer, precautionary measures such as verification of dose distributions using CT images are necessary.

Transitional changes of spacer materials used in carbon-ion radiation therapy.

PURPOSE: To evaluate the imaging findings and transitional changes in spacer materials used in carbon-ion radiation therapy MATERIALS: Medical records were retrospectively reviewed, and the maximum thickness, volume, and CT value of spacers were calculated from CT scans. Procedure-related complications were recorded. RESULTS: A spacer was surgically placed in six patients in retroperitoneal, presacral, or peritoneal sites. The spacer material was polyglycolic acid (PGA) in four patients and expanded polytetrafluoroethylene (ePTFE) in two patients. The thickness of PGA spacers showed no changes in any patients within 4 weeks, but increased within 6 weeks in one patient and was unchanged or decreased in the remaining patients. PGA spacer volume decreased gradually after placement in three of four patients; this was observed at 4 months in two patients and at 6 months in one patient. The mean CT value of PGA spacers was 83 HU just after placement, and decreased gradually thereafter. Air was seen in the PGA spacers of two patients. Neither ePTFE spacer showed volume changes over time, and the mean CT value was low (mean, -53.7 HU) just after placement but increased rapidly to 145 HU at 2 months. CONCLUSION: Spacer imaging findings may vary according to type and may change over time. Familiarity with these features is beneficial for diagnostic radiologists.

Comparison of Clinical Outcomes of Definitive and Postoperative Radiotherapy for Adenoid Cystic Carcinoma of the Head and Neck: Can Definitive Radiotherapy Be a Treatment Option?

BACKGROUND: The standard treatment for adenoid cystic carcinoma of the head and neck is surgical resection followed by postoperative radiotherapy (PORT). Currently, definitive radiotherapy (defRT) is considered an inadequate treatment; however, its data are based on studies using classical radiotherapy techniques. Therefore, the therapeutic effects of current radiotherapy techniques have not been adequately evaluated, and it may have underestimated the efficacy of defRT. METHODS: We retrospectively analyzed 44 adenoid cystic carcinoma patients treated with radiotherapy based on modern treatment techniques from 1993 to 2017. RESULTS: Twenty-four patients underwent PORT and 20 patients underwent defRT. The 5-year overall survival rates for patients treated with PORT and defRT were 85.3% and 79.7%, respectively. The 5-year local control rates were 82.5% and 83.1%, respectively. There were no statistically significant differences in the overall survival and local control of patients treated with PORT and defRT (p = 0.4392 and p = 0.0904, respectively). CONCLUSION: Our results show that defRT is comparable to surgical resection followed by PORT with respect to overall survival and local control. The results suggest that defRT can be an effective treatment option for adenoid cystic carcinoma of the head and neck.

Comparison of Dose Distribution Between VMAT-SBRT and Scanning Carbon-ion Radiotherapy for Early-stage NSCLC.

BACKGROUND/AIM: The purpose of this study was to compare the dose distribution between scanning carbon-ion radiotherapy (sCIRT) and volumetric-modulated arc therapy with stereotactic body radiation therapy (VMAT-SBRT) for stage I non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Fifteen patients with early-stage NSCLC who underwent sCIRT at Kanagawa Cancer Center between 2018-2020 were enrolled. Dose-volume histogram parameters of the planned target volume and normal organs for sCIRT and VMAT-SBRT were evaluated. RESULTS: The homogeneity index of the target volume of sCIRT was significantly lower than that of VMAT-SBRT. The dose of sCIRT was significantly lower than that of VMAT-SBRT at low volumes in the lung, heart, spinal cord, and esophagus. CONCLUSION: The dose distribution of sCIRT for early-stage NSCLC was better than that of VMAT-SBRT.

Interfractional robustness of scanning carbon ion radiotherapy for prostate cancer: An analysis based on dose distribution from daily in-room CT images.

PURPOSE: We analyzed interfractional robustness of scanning carbon ion radiotherapy (CIRT) for prostate cancer based on the dose distribution using daily in-room computed tomography (CT) images. MATERIALS AND METHODS: We analyzed 11 consecutive patients treated with scanning CIRT for localized prostate cancer in our hospital between December 2015 and January 2016. In-room CT images were taken under treatment conditions in every treatment session. The dose distribution on each in-room CT image was recalculated, while retaining the pencil beam arrangement of the initial treatment plan. Then, the dose-volume histogram (DVH) parameters including the percentage of the clinical target volume (CTV) with 95% and 90% of the prescribed dose area (V95% of CTV, V90% of CTV) and V80% of rectum were calculated. The acceptance criteria for the CTV and rectum were set at V95% of CTV ≥95%, V90% of CTV ≥98%, and V80% of rectum < 10 ml. RESULTS: V95% of CTV, V90% of CTV, and V80% of rectum for the reproduced plans were 98.8 ± 3.49%, 99.5 ± 2.15%, and 4.39 ± 3.96 ml, respectively. Acceptance of V95% of CTV, V90% of CTV, and V80% of rectum was obtained in 123 (94%), 125 (95%) and 117 sessions (89%), respectively. Acceptance of the mean dose of V95% of CTV, V90% of CTV, and V80% of rectum for each patient was obtained in 10 (91%), 10 (91%), and 11 patients (100%), respectively. CONCLUSIONS: We demonstrated acceptable interfractional robustness based on the dose distribution in scanning CIRT for prostate cancer.

Dosimetric Comparison of Radiation Therapy Using Hybrid-VMAT Technique for Stage I Esophageal Cancer.

BACKGROUND/AIM: This study focused on the hybrid-volumetric modulated arc therapy (hVMAT) for stage I esophageal cancer and compared the effects on dose distribution induced by changes in the ratio of three-dimensional conformal radiotherapy (3DCRT) to VMAT. PATIENTS AND METHODS: Fifteen patients who underwent 3DCRT for cT1bN0M0 esophageal cancer at Kanagawa Cancer Center from January 2014 to April 2019 were included in the study. The dose-volume histogram (DVH) parameters of the target volume and normal organs were evaluated in the 3DCRT, hVMAT, and VMAT treatment plans. RESULTS: The homogeneity index of the target volume was significantly lower for hVMAT. In hVMAT, as the ratio of VMAT increased, the volume of low-dose region in the heart and lung increased, whereas the volume of the middle- to high-dose region decreased. As the ratio of VMAT increased, the mean dose in the heart decreased, whereas the mean dose in the lung increased. CONCLUSION: Favorable dose concentration was obtained for the target volume in hVMAT for stage I esophageal cancer. Altering the ratio of VMAT significantly changed the DVH parameters in normal organs.

Dosimetric Comparison Between Carbon-ion Radiotherapy and Photon Radiotherapy for Stage I Esophageal Cancer.

BACKGROUND/AIM: The present study aimed to compare the radiation dose distribution of carbon-ion radiotherapy (CIRT) for stage I esophageal cancer with three-dimensional conformal radiotherapy (3DCRT) and volumetric modulated arc therapy (VMAT). PATIENTS AND METHODS: Fifteen patients with cT1bN0M0 esophageal cancer who received 3DCRT at Kanagawa Cancer Center between January 2014 and April 2019 were enrolled. The dose-volume histogram parameters of the target volume and normal organs planned with CIRT, 3DCRT, and VMAT were evaluated. RESULTS: The homogeneity index for the target volume of CIRT was significantly lower than that of 3DCRT and VMAT. In addition, the radiation dose of CIRT to the heart, lungs, spinal cord, and skin was significantly lower than that of 3DCRT and VMAT. CONCLUSION: Favorable dose distributions with CIRT were demonstrated compared with 3DCRT and VMAT for esophageal cancer.

Prostate-specific antigen dynamics after neoadjuvant androgen-deprivation therapy and carbon ion radiotherapy for prostate cancer.

BACKGROUND: This study aimed to explain the dynamics of prostate-specific antigen (PSA) levels in patients with prostate cancer who were treated with carbon ion radiotherapy (CIRT) and neoadjuvant androgen-deprivation therapy (ADT). METHODS: Eighty-five patients with intermediate-risk prostate cancer who received CIRT and neoadjuvant ADT from December 2015 to December 2017 were analyzed in the present study. The total dose of CIRT was set at 51.6 Gy (relative biological effectiveness) delivered in 12 fractions over 3 weeks. The PSA bounce was defined as a ≥0.4 ng/ml increase of PSA levels from the nadir, followed by any decrease. PSA failure was defined using the Phoenix criteria. RESULTS: The median patient age was 68 (range, 48-81) years. The median follow-up duration was 33 (range, 20-48) months. The clinical T stage was T1c, T2a, and T2b in 27, 44, and 14 patients, respectively. The Gleason score was 6 in 3 patients and 7 in 82 patients. The median pretreatment PSA level was 7.37 (range, 3.33-19.0) ng/ml. All patients received neoadjuvant ADT for a median of 6 (range, 2-117) months. PSA bounces were observed in 39 patients (45.9%), occurring a median of 12 (range, 6-30) months after CIRT. PSA failure was observed in eight patients (9.4%), occurring a median of 21 (range, 15-33) months after CIRT. The 3-year PSA failure-free survival rate was 88.5%. No clinical recurrence was observed during the follow-up period. Younger age and lower T stage were significant predictors of PSA bounce. Younger age was a significant predictor of PSA failure. CONCLUSIONS: In this study, we identified the significant predictors of the occurrence of PSA bounce and failure. Further follow-up is needed to reveal the clinical significance of PSA dynamics.

Preliminary result of carbon-ion radiotherapy using the spot scanning method for prostate cancer.

BACKGROUND: Carbon-ion radiotherapy (CIRT) for prostate cancer was initiated at Kanagawa Cancer Center in 2015. The present study analyzed the preliminary clinical outcomes of CIRT for prostate cancer. METHODS: The clinical outcomes of 253 patients with prostate cancer who were treated with CIRT delivered using the spot scanning method between December 2015 and December 2017 were retrospectively analyzed. The irradiation dose was set at 51.6 Gy (relative biological effectiveness) delivered in 12 fractions over 3 weeks. Biochemical relapse was defined using the Phoenix definition. Toxicities were assessed according to CTCAE version 4.0. RESULTS: The median patient age was 70 (47-86) years. The median follow-up duration was 35.3 (4.1-52.9) months. According to the D'Amico classification system, 8, 88, and 157 patients were classified as having low, intermediate, and high risks, respectively. Androgen deprivation therapy was administered in 244 patients. The biochemical relapse-free rate in the low-, intermediate-, and high-risk groups at 3 years was 87.5, 88.0, and 97.5%, respectively (P = 0.036). Grade 2 acute urinary toxicity was observed in 12 (4.7%) patients. Grade 2 acute rectal toxicity was not observed. Grade 2 late urinary toxicity and grade 2 late rectal toxicity were observed in 17 (6.7%) and 3 patients (1.2%), respectively. Previous transurethral resection of the prostate was significantly associated with late grade 2 toxicity in univariate analysis. The predictive factor for late rectal toxicity was not detected. CONCLUSION: The present study demonstrated that CIRT using the spot scanning method for prostate cancer produces favorable outcomes.

Effect of carbon ion radiotherapy for sacral chordoma: results of Phase I-II and Phase II clinical trials.

PURPOSE: To summarize the results of treatment for sacral chordoma in Phase I-II and Phase II carbon ion radiotherapy trials for bone and soft-tissue sarcomas. PATIENTS AND METHODS: We performed a retrospective analysis of 38 patients with medically unresectable sacral chordomas treated with the Heavy Ion Medical Accelerator in Chiba, Japan between 1996 and 2003. Of the 38 patients, 30 had not received previous treatment and 8 had locally recurrent tumor after previous resection. The applied carbon ion dose was 52.8-73.6 Gray equivalents (median, 70.4) in a total of 16 fixed fractions within 4 weeks. RESULTS: The median patient age was 66 years. The cranial tumor extension was S2 or greater in 31 patients. The median clinical target volume was 523 cm(3). The median follow-up period was 80 months. The 5-year overall survival rate was 86%, and the 5-year local control rate was 89%. After treatment, 27 of 30 patients with primary tumor remained ambulatory with or without supportive devices. Two patients experienced severe skin or soft-tissue complications requiring skin grafts. CONCLUSION: Carbon ion radiotherapy appears effective and safe in the treatment of patients with sacral chordoma and offers a promising alternative to surgery.

Dose-volume histogram and dose-surface histogram analysis for skin reactions to carbon ion radiotherapy for bone and soft tissue sarcoma.

BACKGROUND AND PURPOSE: To evaluate the usefulness of the dose-volume histogram (DVH) and dose-surface histogram (DSH) as clinically relevant and available parameters that helped to identify bone and soft tissue sarcoma patients at risk of developing late skin reactions, including ulceration, when treated with carbon ion radiotherapy. MATERIALS AND METHODS: Thirty-five patients with bone and soft tissue sarcoma treated with carbon ion beams were studied. The clinical skin reactions were evaluated. Some pretreatment variables were compared with the grade of late skin reactions. RESULTS: Average DVH and DSH were established in accordance with the grading of the skin reactions. Prescribed dose, the difference in depths between the skin surface and the proximal extent of the tumor, and some DVH/DSH parameters were correlated with late skin reaction (> or = grade 3) according to univariate analysis. Furthermore, the area irradiated with over 60 GyE (S(60)>20 cm(2)) on DSH was the most important factor by multivariate analysis. CONCLUSIONS: The area irradiated with over 60 GyE (S(60)>20 cm(2)) on DSH was found to be a parameter for use as a predictor of late skin reactions.

Changes in tumor volume of sacral chordoma after carbon ion radiotherapy.

OBJECTIVE: We evaluated changes in tumor volume in cases of sacral chordoma after carbon ion radiotherapy. METHODS: Thirty-four patients with sacral chordoma underwent carbon ion radiotherapy between June 1996 and June 2003. We assessed 23 patients without previous surgery using T2-weighted magnetic resonance imaging. The tumor volume was calculated semiautomatically. RESULTS: Two cases showed local recurrence. The median interval of this examination was 46 months. At the end of the treatment, the tumor showed an enlargement larger than 10% of its volume in 13 of the 23 cases, no change in 4 cases, and regression in 6 cases. At the last examination, 20 cases showed a reduction in tumor volume, and the median ratio, determined as the tumor volume at the last examination divided by that before the treatment, was 0.36. CONCLUSIONS: An increase in tumor volume at the end of the treatment does not indicate the ineffectiveness of carbon ion radiotherapy.

Carbon ion radiotherapy for unresectable retroperitoneal sarcomas.

PURPOSE: To evaluate the applicability of carbon ion radiotherapy (CIRT) for unresectable retroperitoneal sarcomas with regard to normal tissue morbidity and local tumor control. METHODS AND MATERIALS: From May 1997 to February 2006, 24 patients (17 male and 7 female) with unresectable retroperitoneal sarcoma received CIRT. Age ranged from 16 to 77 years (median, 48.6 years). Of the patients, 16 had primary disease and 8 recurrent disease. Histologic diagnoses were as follows: malignant fibrous histiocytoma in 6, liposarcoma in 3, malignant peripheral nerve sheath tumor in 3, Ewing/primitive neuroectodermal tumor (PNET) in 2, and miscellaneous in 10 patients. The histologic grades were as follows: Grade 3 in 15, Grade 2-3 in 2, Grade 2 in 3, and unknown in 4. Clinical target volumes ranged between 57 cm(3) and 1,194 cm(3) (median 525 cm(3)). The delivered carbon ion dose ranged from 52.8 to 73.6 GyE in 16 fixed fractions over 4 weeks. RESULTS: The median follow-up was 36 months (range, 6-143 months). The overall survival rates at 2 and 5 years were 75% and 50%, respectively. The local control rates at 2 and 5 years were 77% and 69%. No complications of the gastrointestinal tract were encountered. No other toxicity greater than Grade 2 was observed. CONCLUSIONS: Use of CIRT is suggested to be effective and safe for retroperitoneal sarcomas. The results obtained with CIRT were a good overall survival rate and local control, notwithstanding the fact that most patients were not eligible for surgical resection and had high-grade sarcomas.