Protocol digest of a randomized phase III trial comparing S-1-based chemoradiotherapy with/without nivolumab for unresectable locally advanced or borderline resectable pancreatic cancer: JCOG1908E (PENETRATE).

Pancreatic cancer remains a highly lethal disease with a 5-year survival proportion of <10%. Chemoradiotherapy is a treatment option for unresectable locally advanced (UR-LA) or borderline resectable (BR) pancreatic cancer, but its efficacy is not sufficient. Induction of the synergistic effect of irradiation and immune checkpoint inhibitors can be an attractive strategy. An open-label randomized phase III trial has been conducted since October 2020 to confirm the superiority of nivolumab plus S-1-based chemoradiotherapy over S-1-based chemoradiotherapy alone in patients with UR-LA or BR pancreatic cancer. A total of 216 patients will be enrolled in 14 institutions within 3.5 years. The primary endpoint of the safety run-in part is dose-limiting toxicity, and that of the phase III part is overall survival. This trial was registered at the Japan Registry of Clinical Trials as jRCT2080225361 (https://jrct.niph.go.jp/latest-detail/jRCT2080225361).

Continuous and Early Progression of Carotid Intima-Media Thickness after Radiotherapy for Head and Neck Cancer: 5-Year Prospective Observational Study.

INTRODUCTION: Radiation-induced carotid artery stenosis (RI-CS) is known as one of long-term side effects of radiotherapy for head and neck cancer (HNC). However, the clinical time course after irradiation has been poorly understood. We aimed to investigate the natural history of radiation-induced carotid atherosclerosis, comparing the patients who received radiotherapy for HNC with the patients who were treated without radiotherapy. METHODS: The patients who received treatment of HNC at Department of Otolaryngology, Head and Neck Surgery of Kyoto University Hospital, from November 2012 to July 2015 were enrolled. The patients were assigned into the RT group and the control group, depending on whether radiotherapy was planned or not. Annual carotid ultrasound was performed from the enrollment to 5 years. The increase of mean intima-media thickness (IMT) at common carotid artery from the enrollment (Δmean IMT) was evaluated. RESULTS: Fifty-six patients in the RT group and 25 patients in the control group were enrolled. From 5-year follow-up data, the significant higher increase of Δmean IMT was consistently observed in the RT group than in the control group after 2 years. The RT group presented a 7.8-fold increase of mean IMT compared to the control group (0.060 mm per year in the RT group and 0.008 mm per year in the control group). Cumulative incidence curves obtained from the analysis of all vessels revealed that the RT group presented higher incidence of Δmean IMT ≥0.25 mm than the control group (p < 0.01). In the RT group, the patients with mean IMT ≥1.0 mm at enrollment exhibited significantly higher incidence of Δmean IMT ≥0.25 mm than the patients with mean IMT <1.0 mm (p < 0.01). DISCUSSION: Radiotherapy for HNC induces continuous carotid mean IMT progression. The irradiated carotid arteries with mean IMT ≥1.0 mm before radiotherapy presented earlier IMT progression than those with mean IMT <1.0 mm.

Multi-institutional phase II study of ultra-hypofractionated whole-breast irradiation after breast-conserving surgery for breast cancer in Japan: Kyoto Radiation Oncology Study Group (UPBEAT study).

PURPOSE: The UK-FAST-Forward study showed that ultra-hypofractionated whole-breast irradiation (ultra-HF-WBI) involving five fractions of 26 Gy radiation over 1 week was not inferior to HF-WBI. However, it is not used in Japan due to safety concerns. In April 2022, we commenced a multi-institutional, single-arm, phase II trial. Our aim is to confirm the safety of ultra-HF-WBI after breast-conserving surgery (BCS) for breast cancer in Japanese women. METHOD: We plan to enroll 98 patients from 13 institutions. The primary endpoint is the proportion of late adverse events of grades ≥2 within 3 years. DISCUSSION: We believe that this highly promising clinical study can positively impact the Japanese guidelines for breast cancer treatment. The results will help us decide whether or not ultra-HF-WBI can be used as a more convenient alternative to WBI. REGISTRATION NUMBER AND DATE: This trial was registered in the UMIN Clinical Trials Registry (UMIN000047080) on March 4, 2022.

The mutual relationship between the host immune system and radiotherapy: stimulating the action of immune cells by irradiation.

The effects of irradiation on tumor tissue and the host immune system are interrelated. The antitumor effect of irradiation is attenuated in the immunocompromised hosts. In addition, radiation alone positively and negatively influences the host immune system. The positive effects of radiation are summarized by the ability to help induce and enhance tumor-antigen-specific immune responses. The cancer-immunity cycle is a multistep framework that illustrates how the tumor-antigen-specific immune responses are induced and how the induced antigen-specific immune cells exert their functions in tumor tissues. Irradiation affects each step of this cancer-immunity cycle, primarily in a positive manner. In contrast, radiation also has negative effects on the immune system. The first is that irradiation has the possibility to kill irradiated effector immune cells. The second is that irradiation upregulates immunosuppressive molecules in the tumor microenvironment, whereas the third is that irradiation to the tumor condenses immunosuppressor cells in the tumor microenvironment. When used in conjunction with radiotherapy, immune checkpoint inhibitors can further leverage the positive effects of radiation on the immune system and compensate for the negative effects of irradiation, which supports the rationale for the combination of radiotherapy and immune checkpoint inhibitors. In this review, we summarize the preclinical evidence for the reciprocal effects of radiation exposure and the immune system, and up-front topics of the combination therapy of immune checkpoint inhibitors and radiotherapy.

Potential utility of cone-beam CT-guided adaptive radiotherapy under end-exhalation breath-hold conditions for pancreatic cancer.

PURPOSE: The purpose of this study was to demonstrate the potential utility of cone-beam computed tomography (CBCT)-guided online adaptive radiotherapy (ART) under end-exhalation breath-hold (EE-BH) conditions for pancreatic cancer (PC). METHODS: Eleven PC patients who underwent 15-fraction volumetric-modulated arc therapy under EE-BH conditions were included. Planning CT images and daily 165 CBCT images were imported into a dedicated treatment planning system. The prescription dose was set to 48 Gy in 15 fractions. The reference plan was automatically generated along with predefined clinical goals. After segmentation was completed on CBCT images, two different plans were generated: One was an adapted (ADP) plan in which re-optimization was performed on the anatomy of the day, and the other was a scheduled (SCH) plan, which was the same as the reference plan. The dose distributions calculated using the synthetic CT created from both planning CT and CBCT were compared between the two plans. Independent calculation-based quality assurance was also performed for the ADP plans, with a gamma passing rate of 3%/3 mm. RESULTS: All clinical goals were successfully achieved during the reference plan generation. Of the 165 sessions, gross tumor volume D98% and clinical target volume D98% were higher in 100 (60.1%) and 122 (74.0%) ADP fractions. In each fraction, the V3 Gy  < 1 cm3 of the stomach and duodenum was violated in 47 (28.5%) and 48 (29.1%), respectively, of the SCH fractions, whereas no violations were observed in the ADP fractions. There were statistically significant differences in the dose-volume indices between the SCH and ADP fractions (p < 0.05). The gamma passing rates were above 95% in all ADP fractions. CONCLUSIONS: The CBCT-guided online ART under EE-BH conditions successfully reduced the dose to the stomach and duodenum while maintaining target coverage.

Impact of neoadjuvant intensity-modulated radiation therapy on borderline resectable pancreatic cancer with arterial abutment; a prospective, open-label, phase II study in a single institution.

BACKGROUND: Borderline resectable pancreatic cancer (BRPC) is a category of pancreatic cancer that is anatomically widely spread, and curative resection is uncommon with upfront surgery. Intensity-modulated radiation therapy (IMRT) is a form of radiation therapy that delivers precise radiation to a tumor while minimizing the dose to surrounding normal tissues. Here, we conducted a phase 2 study to estimate the curability and efficacy of neoadjuvant chemoradiotherapy using IMRT (NACIMRT) for patients with BRPC with arterial abutment (BRPC-A). METHODS: A total of 49 BRPC-A patients were enrolled in this study and were treated at our hospital according to the study protocol between June 2013 and March 2021. The primary endpoint was microscopically margin-negative resection (R0) rates and we subsequently analyzed safety, histological effect of the treatment as well as survivals among patients with NACIMRT. RESULTS: Twenty-nine patients (59.2%) received pancreatectomy after NACIMRT. The R0 rate in resection patients was 93.1% and that in the whole cohort was 55.1%. No mortality was encountered. Local therapeutic effects as assessed by Evans classification showed good therapeutic effect (Grade 1, 3.4%; Grade 2a, 31.0%; Grade 2b, 48.3%; Grade 3, 3.4%; Grade 4, 3.4%). Median disease-free survival was 15.5 months. Median overall survival in the whole cohort was 35.1 months. The only independent prognostic pre-NACIMRT factor identified was serum carbohydrate antigen 19-9 (CA19-9) > 400 U/ml before NACIMRT. CONCLUSIONS: NACIMRT showed preferable outcome without significant operative morbidity for BRPC-A patients. NACIMRT contributes to good local tumor control, but a high initial serum CA19-9 implies poor prognosis even after neoadjuvant treatment. TRIAL REGISTRATION: UMIN-CTR Clinical Trial: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000011776 Registration number: UMIN000010113. Date of first registration: 01/03/2013.

Reducing variability among treatment machines using knowledge-based planning for head and neck, pancreatic, and rectal cancer.

PURPOSE: This study aimed to assess dosimetric indices of RapidPlan model-based plans for different energies (6, 8, 10, and 15 MV; 6- and 10-MV flattening filter-free), multileaf collimator (MLC) types (Millennium 120, High Definition 120, dual-layer MLC), and disease sites (head and neck, pancreatic, and rectal cancer) and compare these parameters with those of clinical plans. METHODS: RapidPlan models in the Eclipse version 15.6 were used with the data of 28, 42, and 20 patients with head and neck, pancreatic, and rectal cancer, respectively. RapidPlan models of head and neck, pancreatic, and rectal cancer were created for TrueBeam STx (High Definition 120) with 6 MV, TrueBeam STx with 10-MV flattening filter-free, and Clinac iX (Millennium 120) with 15 MV, respectively. The models were used to create volumetric-modulated arc therapy plans for a 10-patient test dataset using all energy and MLC types at all disease sites. The Holm test was used to compare multiple dosimetric indices in different treatment machines and energy types. RESULTS: The dosimetric indices for planning target volume and organs at risk in RapidPlan model-based plans were comparable to those in the clinical plan. Furthermore, no dose difference was observed among the RapidPlan models. The variability among RapidPlan models was consistent regardless of the treatment machines, MLC types, and energy. CONCLUSIONS: Dosimetric indices of RapidPlan model-based plans appear to be comparable to the ones based on clinical plans regardless of energies, MLC types, and disease sites. The results suggest that the RapidPlan model can generate treatment plans independent of the type of treatment machine.

A phase II study of adaptive two-step intensity-modulated radiation therapy (IMRT) with chemotherapy for loco-regionally advanced nasopharyngeal cancer (JCOG1015).

BACKGROUND: A phase II study of adaptive two-step intensity-modulated radiotherapy (IMRT) with chemotherapy for nasopharyngeal cancer (NPC) (JCOG1015) was conducted to evaluate the efficacy and safety. METHODS: Patients aged 20-75 years with stages II-IVB NPC were enrolled. As adaptive two-step IMRT, computed tomography planning was performed twice before IMRT for the initial plan of 46 Gy/23 fractions and during treatment for the boost plan of 24 Gy/12 fractions with a total dose of 70 Gy. Chemotherapy (cisplatin 80 mg/m2/3-weeks × 3 courses) was administered concurrently with IMRT, followed by adjuvant chemotherapy (cisplatin at 70 mg/m2 with 5-FU 700 at mg/m2 for 5 days/4 weeks × 3 courses). RESULTS: Between 2011 and 2014, 75 patients were enrolled from 12 institutions. The 3-year overall survival (OS) for the 75 patients was 88%, and the upper and lower limits of the 95% CI of 78%-94% were higher than the expected 3-year OS of 75% for the target population adjusted by the actual proportion of stage II:III:IV = 21%:44%:35%. The 3-year progression-free survival (PFS) and loco-regional PFS were 71% [59-80%] and 77% [66-85%], respectively. Although no grade 4-5 late toxicities were observed, 15 patients (20%) developed grade 3 late toxicities. Grade 2 xerostomia was noted in 26%, 12%, and 9% at 1, 2, and 3 years after starting IMRT, respectively. CONCLUSIONS: Adaptive two-step IMRT for NPC demonstrated an excellent 3-year OS with acceptable toxicities. This method may be one treatment option for locally advanced NPC.

Impact of interfractional anatomical variation and setup correction methods on interfractional dose variation in IMPT and VMAT plans for pancreatic cancer patients: A planning study.

PURPOSE: To investigate the impact of interfractional anatomical changes and setup correction methods on dose distributions in pancreatic cancer patients under breath-hold conditions. METHODS: Three intensity-modulated proton therapy (IMPT) plans with different beam arrangements and one volumetric-modulated arc therapy (VMAT) plan prescribing 54 Gy in 30 fractions were created for 10 patients who underwent three additional CT scans performed at an interval of 1-2 weeks. The additional CT sets were rigidly registered to the simulation CT set using both bone-matching (BM) and organ-matching (OM) methods in each patient. Recalculated dose distributions and dose-volume indices on the additional CT sets using either the BM or the OM method were compared with the simulation values. RESULTS: Differences in the gross tumor volume D98% value from the simulation sets ranged from -0.8 to -5.9% on average. In addition, the variations were larger with OM compared with BM for two IMPT plans. Meanwhile, differences in the D98% value in the region isotropically enlarged by 5 mm from the gross tumor volume were significantly improved with OM on two IMPT plans and the VMAT plan. Among the organs at risk, the dose-volume indices were significantly improved with OM only in the duodenum on all plans. CONCLUSION: Organ-matching may be a better setup correction technique than BM for both photon therapy and IMPT plans. However, in some beam arrangements of IMPT, the dose distribution may be somewhat worse using OM, due to interfractional anatomical variation. Therefore, it is important to choose beam angles that are less likely to be influenced by changes in the gastrointestinal gas volume, especially in IMPT plans.

Analyses of integrated EPID images for on-treatment quality assurance to account for interfractional variations in volumetric modulated arc therapy.

PURPOSE: To investigate the effects of interfractional variation, such as anatomical changes and setup errors, on dose delivery during treatment for prostate cancer (PC) and head and neck cancer (HNC) by courses of volumetric modulated arc therapy (VMAT) aided by on-treatment electronic portal imaging device (EPID) images. METHODS: Seven patients with PC and 20 patients with HNC who had received VMAT participated in this study. After obtaining photon fluence at the position of the EPID for each treatment arc from on-treatment integrated EPID images, we calculated the differences between the fluence for the first fraction and each subsequent fraction for each arc. The passing rates were investigated based on a tolerance level of 3% of the maximum fluence during the treatment courses and the correlations between the passing rates and anatomical changes. RESULTS: In PC, the median and lowest passing rates were 99.8% and 95.2%, respectively. No correlations between passing rates and interfractional variation were found. In HNC, the median passing rate of all fractions was 93.0%, and the lowest passing rate was 79.6% during the 35th fraction. Spearman's correlation coefficients between the passing rates and changes in weight or neck volume were - 0.77 and - 0.74, respectively. CONCLUSIONS: Analyses of the on-treatment EPID images facilitates estimates of the interfractional anatomical variation in HNC patients during VMAT and thus improves assessments of the need for re-planning or adaptive strategies and the timing thereof.

Factors associated with a preference for disclosure of life expectancy information from physicians: a cross-sectional survey of cancer patients undergoing radiation therapy.

PURPOSE: This study aimed to investigate experiences and preferences for disclosure of life expectancy, agreement between them, and the factors associated with preferences for disclosure of life expectancy with physicians among cancer patients undergoing radiation therapy. METHODS: Cancer patients aged 20 years or older were consecutively sampled when they started radiation therapy at two university hospitals. Patients completed self-administered questionnaires concerning their experiences of and preferences for disclosure of life expectancy, treatment decision-making, psychological distress, physical symptoms, sociodemographic and medical factors, physician's communication style, and provision of psychological, physical, and practical support. RESULTS: Among the 226 respondents (response rate: 58%) who responded, 54% experienced disclosure of life expectancy, and 45% preferred it. The agreement is 65%. Eighty-five percent recognized their aim of radiation therapy as curative. A univariate analysis indicated that having a full/part-time job and wishing to leave treatment decisions to doctors were significantly associated with preference for disclosure of life expectancy, but psychological distress was not. A multiple regression analysis revealed that having a full-time/part-time job was significantly associated with preference of communication about life expectancy. CONCLUSIONS: Fifty-four percent of the patients experienced and 45% of the patients preferred disclosure of life expectancy. The agreement is moderate. Our results show that there was a significant association between employment status and patient's preference for disclosure of life expectancy with physicians. Communication of prognosis is difficult but whether a patient continues to work or not may be an indicator of preference.

A cross-sectional study of agreement between the Hospital Anxiety and Depression Scale and patient- and radiation oncologist-reported single-item assessment of depression and anxiety.

OBJECTIVE: To describe among radiation oncology patients: (1) the proportion likely to be experiencing symptoms of depression and anxiety as identified by (a) the Hospital Anxiety and Depression Scale (HADS; standardised tool), (b) patient-reported single items (ultrashort tool), and (c) radiation oncologist-reported single items (clinician judgement); (2) preferences for being offered psychological support; and (3) agreement between single-item measures and the HADS. METHODS: Adult cancer patients (n = 152; consent rate 58%) receiving radiotherapy completed a touchscreen tablet survey assessing symptoms of anxiety and depression (HADS and a single-item tool) and support preferences. Each participant's treating radiation oncologist completed a survey assessing his or her perception of whether the patient was anxious or depressed. RESULTS: Prevalence estimates for likely depression (6.9-18%) and anxiety (17-33%) overlapped across the 3 measures. Overall, only 9.9% of patients (95% CI, 5.6%-16%) wanted to be offered psychological support. For depression, agreement between the HADS and ultrashort tool was fair (κ = 0.37, P < 0.0001); agreement between the HADS and clinician judgement was slight (κ = 0.14, P < 0.05). For anxiety, agreement between the HADS and clinician judgement was not significantly greater than chance alone (κ = 0.04, P = 0.33), and agreement between the HADS and ultrashort tool was moderate (κ = 0.49, P < 0.0001). CONCLUSIONS: These findings highlight the important role that oncology consultations play in interpreting assessment tool results and responding to individual patient's history and preferences for psychological support.

Personalization of loco-regional care for primary breast cancer patients (part 1).

ABSTRACT Kyoto Breast Cancer Consensus Conference, Kyoto, Japan, 18-20 February 2014 The loco-regional management of breast cancer is increasingly complex with application of primary systemic therapies, oncoplastic techniques and genetic testing for breast cancer susceptibility. Personalization of loco-regional treatment is integral to optimization of breast cancer care. Clinical and pathological tumor stage, biological features and host factors influence loco-regional treatment strategies and extent of surgical procedures. Key issues including axillary staging, axillary treatment, radiation therapy, primary systemic therapy (PST), preoperative hormonal therapy and genetic predisposition were identified and discussed at the Kyoto Breast Cancer Consensus Conference (KBCCC2014). In the first of a two part conference scene, consensus recommendations for axillary management are presented and focus on the following topics: indications for completion axillary lymph node dissection in primary surgical patients with ≤2 macrometastases or any sentinel nodal deposits after PST; the timing of sentinel lymph node biopsy in the context of PST; use of axillary irradiation as a component of primary treatment plans and the role of intraoperative node assessment in the post-Z0011 era.

Personalization of loco-regional care for primary breast cancer patients (part 2).

Kyoto Breast Cancer Consensus Conference, Kyoto, Japan, 18-20 February 2014 The loco-regional management of breast cancer is increasingly complex with application of primary systemic therapies, oncoplastic techniques and genetic testing for breast cancer susceptibility. Personalization of loco-regional treatment is integral to optimization of breast cancer care. Clinical and pathological tumor stage, biological features and host factors influence loco-regional treatment strategies and extent of surgical procedures. Key issues including axillary staging, axillary treatment, radiation therapy, primary systemic therapy (PST), preoperative hormonal therapy and genetic predisposition were identified and discussed at the Kyoto Breast Cancer Consensus Conference (KBCCC2014). In the second of a two part conference scene, consensus recommendations for radiation treatment, primary systemic therapies and management of genetic predisposition are reported and focus on the following topics: influence of both clinical response to PST and stage at presentation on recommendations for postmastectomy radiotherapy; use of regional nodal irradiation in selected node-positive patients and those with adverse pathological factors; extent of surgical resection following downstaging of tumors with PST; use of preoperative hormonal therapy in premenopausal women with larger, node-negative luminal A-like tumors and managing increasing demands for contralateral prophylactic mastectomy in patients with a unilateral sporadic breast cancer.

Dosimetric evaluation of the Acuros XB algorithm for a 4 MV photon beam in head and neck intensity-modulated radiation therapy.

In this study, we assessed the differences in the dose distribution of a 4 MV photon beam among different calculation algorithms: the Acuros XB (AXB) algorithm, the analytic anisotropic algorithm (AAA), and the pencil beam convolution (PBC) algorithm (ver. 11.0.31), in phantoms and in clinical intensity-modulated radiation therapy (IMRT) plans. Homogeneous and heterogeneous, including middle-, low-, and high-density, phantoms were combined to assess the percentage depth dose and lateral dose profiles among AXB, AAA, and PBC. For the phantom containing the low-density area, AXB was in agreement with measurement within 0.5%, while the greatest differences between the AAA and PBC calculations and measurement were 2.7% and 3.6%, respectively. AXB showed agreement with measurement within 2.5% at the high-density area, while AAA and PBC overestimated the dose by more than 4.5% and 4.0%, respectively. Furthermore, 15 IMRT plans, calculated using AXB, for oropharyngeal, hypopharyngeal, and laryngeal carcinomas were analyzed. The dose prescription was 70 Gy to 50% of the planning target volume (PTV70). Subsequently, each plan was recalculated using AAA and PBC while maintaining the AXB-calculated monitor units, leaf motion, and beam arrangement. Additionally, nine hypopharyngeal and laryngeal cancer patients were analyzed in terms of PTV70 for cartilaginous structures (PTV(70_cartilage)). The doses covering 50% to PTV70 calculated by AAA and PBC were 2.1% ± 1.0% and 3.7% ± 0.8% significantly higher than those using AXB, respectively (p < 0.01). The increases in doses to PTV(70_cartilage) calculated by AAA and PBC relative to AXB were 3.9% and 5.3% on average, respectively, and were relatively greater than those in the entire PTV70. AXB was found to be in better agreement with measurement in phantoms in heterogeneous areas for the 4 MV photon beam. Considering AXB as the standard, AAA and PBC overestimated the IMRT dose for head and neck cancer. The dosimetric differences should not be ignored, particularly with cartilaginous structures in PTV.

Radiotherapy for patients with isolated local recurrence of primary resected pancreatic cancer. Prolonged disease-free interval associated with favorable prognosis.

BACKGROUND AND PURPOSE: To evaluate the treatment outcomes of radiotherapy and prognostic factors for recurrent pancreatic cancer. PATIENTS AND METHODS: The study comprised 30 patients who developed a locoregional recurrence of primarily resected pancreatic cancer and received radiotherapy between 2000 and 2013 with a median dose of 54 Gy (range, 39-60 Gy). Concurrent chemotherapy included gemcitabine for 18 patients and S-1 for seven patients. The treatment outcomes and prognostic factors were retrospectively analyzed. RESULTS: The median follow-up after radiotherapy was 14.6 months. The 1-year overall survival, local control, and progression-free survival rates were 69%, 67%, and 32%, respectively. The median overall survival and progression-free survival rates were 15.9 and 6.9 months, respectively. Tumor marker reduction and ≥ 50% reduction were observed in 18 and two patients, respectively. Of the seven patients who exhibited pain symptoms, four and two patients were partly and completely relieved, respectively. Late grade 3 ileus and gastroduodenal bleeding were observed in one patient each. Among the clinicopathological factors evaluated, only a disease-free interval of greater than 18.9 months exhibited a significant association with improved overall survival (p = 0.017). CONCLUSIONS: Radiotherapy for isolated locally recurrent pancreatic cancer resulted in encouraging local control, overall survival, and palliative effects with mild toxicity, particularly in patients with a prolonged disease-free interval. This treatment strategy should be prospectively evaluated.

[Use of surgical clips to verify positional accuracy in image-guided accelerated partial breast irradiation].

The purpose of this study was to evaluate the accuracy of positional verification during overall radiation treatment periods in accelerated partial breast irradiation using one or more surgical clips. We first investigated the appropriate computed tomography (CT) slice thickness and detectability of clips for a matching criterion in a phantom study. Next, clinical investigations were carried on 12 patients with multiple clips positioned around the lumpectomy cavity. During radiation treatment planning, a 5-mm region of interest (5-mm ROI) was defined by adding a three dimentional (3D) margin of 5 mm to each clip. During treatment, the clips on two orthogonal kilovoltage X-ray images acquired were moved so as to be included in the corresponding 5-mm ROI on digitally reconstructed radiographs (DRRs). Positional accuracy was calculated using the displacement of each clip in the verification images. The displacements of each clip acquired in all setups were then calculated throughout the overall radiation treatment period and the factors affecting the displacement of clips were investigated. Positional accuracy was also investigated in setups using skin marks and in setups using the bone structure around the thorax. We demonstrated in a phantom study that a CT slice thickness of 2.5 mm was appropriate. In our clinical investigations, 91% of the clips were included in the 5-mm ROI. The interfractional displacement of clips was large, with a long distance between the isocenter and each clip at the time of radiation treatment planning.

Long-term outcomes of stimulated salivary flow and xerostomia after definitive intensity-modulated radiation therapy for patients with head and neck cancer†.

This retrospective study aimed to evaluate the time to recovery from xerostomia and analyze its predictors, along with long-term outcomes of stimulated salivary flow after intensity-modulated radiation therapy (IMRT) for head and neck cancer (HNC). We evaluated patients with HNC who had received IMRT with curative intent between 2012 and 2018 at our institution. The salivary recovery ratio (SRR) was defined as '(the stimulated salivary flow)/(pre-treatment salivary flow)'. The cutoff value of SRR in salivary recovery was estimated via the relationship between SRR and xerostomia grades. The salivary recovery time was defined as the time for SRR to exceed cutoff values from the end of radiotherapy. Fifty-seven patients were analyzed, with a 48-month median follow-up period of stimulated salivary flow. The cutoff value for SRR was 44.8%, and patients with a higher grade of xerostomia had a lower SRR (P < 0.001). The median salivary recovery time was 12 months. The cumulative incidence rates of salivary recovery at two and four years were 84 (95% confidence interval [CI]: 53-79) and 92% (95% CI: 82-97), respectively, and these were significantly lower in patients with a higher mean parotid gland dose, mean oral cavity dose and stimulated salivary flow per parotid gland volume. Stimulated salivary flow and xerostomia recover over a long period after radiotherapy.

Population-based asymmetric margins for moving targets in real-time tumor tracking.

BACKGROUND: Both geometric and dosimetric components are commonly considered when determining the margin for planning target volume (PTV). As dose distribution is shaped by controlling beam aperture in peripheral dose prescription and dose-escalated simultaneously integrated boost techniques, adjusting the margin by incorporating the variable dosimetric component into the PTV margin is inappropriate; therefore, geometric components should be accurately estimated for margin calculations. PURPOSE: We introduced an asymmetric margin-calculation theory using the guide to the expression of uncertainty in measurement (GUM) and intra-fractional motion. The margins in fiducial marker-based real-time tumor tracking (RTTT) for lung, liver, and pancreatic cancers were calculated and were then evaluated using Monte Carlo (MC) simulations. METHODS: A total of 74 705, 73 235, and 164 968 sets of intra- and inter-fractional positional data were analyzed for 48 lung, 48 liver, and 25 pancreatic cancer patients, respectively, in RTTT clinical trials. The 2.5th and 97.5th percentiles of the positional error were considered representative values of each fraction of the disease site. The population-based statistics of the probability distributions of these representative positional errors (PD-RPEs) were calculated in six directions. A margin covering 95% of the population was calculated using the proposed formula. The content rate in which the clinical target volume (CTV) was included in the PTV was calculated through MC simulations using the PD-RPEs. RESULTS: The margins required for RTTT were at most 6.2, 4.6, and 3.9 mm for lung, liver, and pancreatic cancer, respectively. MC simulations revealed that the median content rates using the proposed margins satisfied 95% for lung and liver cancers and 93% for pancreatic cancer, closer to the expected rates than the margins according to van Herk's formula. CONCLUSIONS: Our proposed formula based on the GUM and motion probability distributions (MPD) accurately calculated the practical margin size for fiducial marker-based RTTT. This was verified through MC simulations.