Efficacy and safety of FDG-PET for determining target volume during intensity-modulated radiotherapy for head and neck cancer involving the oral level.

PURPOSE: To determine the efficacy and safety of target volume determination by 18F-fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) for intensity-modulated radiation therapy (IMRT) for locally advanced head and neck squamous cell carcinoma (HNSCC) extending into the oral cavity or oropharynx. METHODS: We prospectively treated 10 consecutive consenting patients with HNSCC using IMRT, with target volumes determined by PET-CT. Gross tumor volume (GTV) and clinical target volume (CTV) at the oral level were determined by two radiation oncologists for CT, magnetic resonance imaging (MRI), and PET-CT. Differences in target volume (GTVPET, GTVCT, GTVMRI, CTVPET, CTVCT, and CTVMRI) for each modality and the interobserver variability of the target volume were evaluated using the Dice similarity coefficient and Hausdorff distance. Clinical outcomes, including acute adverse events (AEs) and local control were evaluated. RESULTS: The mean GTV was smallest for GTVPET, followed by GTVCT and GTVMRI. There was a significant difference between GTVPET and GTVMRI, but not between the other two groups. The interobserver variability of target volume with PET-CT was significantly less than that with CT or MRI for GTV and tended to be less for CTV, but there was no significant difference in CTV between the modalities. Grade ≤ 3 acute dermatitis, mucositis, and dysphagia occurred in 55%, 88%, and 22% of patients, respectively, but no grade 4 AEs were observed. There was no local recurrence at the oral level after a median follow-up period of 37 months (range, 15-55 months). CONCLUSIONS: The results suggest that the target volume determined by PET-CT could safely reduce GTV size and interobserver variability in patients with locally advanced HNSCC extending into the oral cavity or oropharynx undergoing IMRT. Trial registration UMIN, UMIN000033007. Registered 16 jun 2018, https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000037631.

Hands-on-training tailored in response to pre-questionnaire-based survey on image-guided brachytherapy effectively reduces anxiety about its implementation.

This study assessed the significance of hands-on-training (HoT) and questionnaire-based surveys on 3D image-guided brachytherapy (3D-IGBT) and a combination of intracavitary and interstitial brachytherapy, the so-called 'hybrid' BT (HBT), in uterine cervical cancer. In October 2023, 29 radiation oncologists, nurses, radiologic technologists and medical physicists from 10 Japanese facilities participated in an HoT on 3D-IGBT and HBT. Questionnaires were distributed to each participant before and after the HoT, and feedback was obtained through online channels. The questionnaire response rate was 83% (24/29), with at least one participant responding from each facility. 'Insertion of applicators and needles', 'human resource shortage' and 'pain relief and sedation' were the primary concerns of radiation oncologists. 'Applicator reconstruction', ' optimization of dwell positions', ' treatment planning' and ' human resource shortages ' were the primary concerns of radiological technologists and medical physicists. The HoT content was adjusted according to the results of preliminary surveys. The concerns expressed by the participants were addressed during the lectures and practical training. Significant reductions in anxiety were observed toward all items of the 10-point self-assessment after the HoT, regardless of the profession. The average score on satisfaction with the HoT (on a 10-point scale) was 9.52 (minimum of 8 and maximum of 10). In conclusion, HoT tailored in response to a pre-questionnaire-based survey effectively reduced participants' anxiety regarding the implementation of 3D-IGBT and HBT.

Safe dose escalation and reduction of the fraction number of uterine cervical brachytherapy using a gel spacer in the rectovaginal and vesicouterine septum: A planning study.

PURPOSE: To evaluate the possibility of dose escalation and reduction of fraction number in cervical brachytherapy using a gel spacer. MATERIAL AND METHODS: Twenty patients with uterine cervical cancer treated with image-guided adaptive brachytherapy (IGABT) were selected. Hyaluronic acid gel injection (HGI) was performed in the rectovaginal and vesicouterine septum for 10 patients. The other ten patients were not with HGI. Both groups were treated with IGABT involving tandem/ovoid or cylindrical applicators along with additional interstitial needles. Dose distributions approved by radiation oncologists were retrospectively analyzed, and a dose summation of 45 Gy/25 of external beam radiation therapy and IGABT was performed. Dose constraints for D2cc of bladder, rectum, and sigmoid were 80, 70, and 70 Gy, respectively. Equivalent dose in 2-Gy fractions calculations used α/ß = 10 Gy for high-risk clinical target volume (CTVHR) D90 and α/ß = 3 Gy for organs at risks (OARs). As a planning study, dose distribution rescaling was conducted to deliver as much dose to CTVHR D90 as possible within the dose constraint limitation for OARs when IGABT was performed for four, three, and two fractions in both groups. RESULTS: The median CTVHR D90 was >80 Gy in the non-HGI group and >85 Gy in the HGI group for virtual two and three fractions. Rectum D2cc was significantly lower in the HGI group for three fractions (p < 0.01). CONCLUSIONS: In the HGI group, adequate dose delivery to CTVHR could be achieved with a reduced IGABT fraction number while meeting the dose constraints of OARs.

Dosimetric comparison of four-dimensional computed tomography based internal target volume against variations in respiratory motion during treatment between volumetric modulated arc therapy and three-dimensional conformal radiotherapy in lung stereotactic body radiotherapy.

This study focused on the dosimetric impact of variations in respiratory motion during lung stereotactic body radiotherapy (SBRT). Dosimetric comparisons between volumetric modulated arc therapy (VMAT) and three-dimensional conformal radiotherapy (3DCRT) were performed using four-dimensional computed tomography (4DCT)-based internal target volumes (ITV). We created retrospective plans for ten patients with lung cancer who underwent SBRT using 3DCRT and VMAT techniques. A Delta4 Phantom + (ScandiDos, Uppsala, Sweden) was used to evaluate the dosimetric robustness of 4DCT-based ITV against variations in respiratory motion during treatment. We analyzed respiratory motion during treatment. Dose-volume histogram parameters were evaluated for the 95% dose (D95%) to the planning target volume (PTV) contoured on CT images obtained under free breathing. The correlations between patient respiratory parameters and dosimetric errors were also evaluated. In the phantom study, the average PTV D95% dose differences for all fractions were - 2.9 ± 4.4% (- 16.0 - 1.2%) and - 2.0 ± 2.8% (- 11.2 - 0.7%) for 3DCRT and VMAT, respectively. The average dose difference was < 3% for both 3DCRT and VMAT; however, in 5 out of 42 fractions in 3DCRT, the difference in PTV D95% was > 10%. Dosimetric errors were correlated with respiratory amplitude and velocity, and differences in respiratory amplitude between 4DCT and treatment days were the main factors causing dosimetric errors. The overall average dose error of the PTV D95% was small; however, both 3DCRT and VMAT cases exceeding 10% error were observed. Larger errors occurred with amplitude variation or baseline drift, indicating limited robustness of 4DCT-based ITV.

MucoUp® as a spacer in brachytherapy for uterine cervical cancer: A first-in-human experience.

We first used MucoUp®, a hyaluronic acid used in endoscopic resection, as a spacer in brachytherapy. In five cervical cancer patients, MucoUp® insertion increased a 90% dose of the high-risk CTV to over 80 Gy while decreasing the dose of organs at risk. No related adverse events were observed.

Palliative Radiotherapy Induced Severe Tumor Lysis Syndrome in a Patient With Multiple Myeloma With Skin Involvement: A Case Report and Review of Literature.

BACKGROUND/AIM: Radiotherapy (RT) has been rarely reported as a cause of tumor lysis syndrome (TLS). Therefore, the patient characteristics and details of RT-induced TLS remain unclear, which may delay diagnosis. Herein, we report a case of palliative RT-induced severe TLS in a patient with multiple myeloma (MM) with skin involvement along with literature review. CASE REPORT: A 75-year-old female with MM was referred to our department in February 2021 because of swelling and pruritus of the bulky tumor on her right breast and severe left leg pain. She had received chemotherapies and autologous peripheral blood stem cell transplantations since October 2012. We administered palliative RT (a single 8 Gy fraction) to the right breast, left tibia, and femur. On day 7 after RT, a shrinkage effect was observed on the right breast lesion, and left leg pain was relieved. Her laboratory results showed hyperuricemia, hyperphosphatemia, and hypercreatininemia. Initially, we considered acute renal failure (ARF) due to MM progression and planned for a follow-up after 1 week. On day 14 after RT completion, she experienced vomiting and anorexia. Her laboratory results became worse. She was admitted with the diagnosis of TLS and received intravenous fluid hydration and allopurinol. Unfortunately, the evolution was marked by severe clinical deterioration with anuria and coma, leading to death on day 35 after RT. CONCLUSION: It is important to determine whether ARF is due to MM progression or TLS. The occurrence of TLS should be considered in the case of a rapidly shrinking bulky tumor while receiving palliative RT.

Development of deep-inspiration breath-hold system that monitors the position of the chest wall using infrared rangefinder.

We conducted a prospective study to quantitatively evaluate the movement of the chest wall to establish the simple and reproducible deep-inspiration breath-hold (DIBH) method. The left nipple position was monitored to confirm the inspiratory state. Planning computed tomography (CT) was performed under DIBH and free-breath. We conducted radiation plans with DIBH and free-breath CT and evaluated organ at risk (OAR) and target doses according to two different plans. The relationship between positioning errors of the chest wall and patient factors was evaluated using univariate analysis and fixed-effects models. Twenty-three patients aged ≤ 60 years were enrolled during January-August 2021; 358 daily radiation treatments were evaluated. The median time of treatment room occupancy was 16 minutes (interquartile range, 14-20). The area of the planning target volume (PTV) surrounded by the 95% isodose line was more extensive in DIBH than in free breathing (71.6% vs 69.5%, P < 0.01), whereas the cardiac and left anterior descending (LAD) artery doses were lower (both P < 0.01). In the fixed-effects model analysis, the occupation time of the treatment room was correlated with positioning error. The difference between the planned and irradiated dose was the largest in the LAD branch of the coronary artery (-2.5 Gy), although the OAR dose decreased owing to positional error. The current DIBH method, wherein a single point on the chest wall is monitored to confirm that the patient is in an inspiratory state, allows radiation to be performed in a short time with a small dose error.

Clinical outcomes of definitive radiotherapy for patients with cT1aN0M0 esophageal cancer unsuitable for endoscopic resection and surgery.

Background: Studies on the clinical outcomes of radiotherapy for clinical (c)T1aN0M0 (UICC-TNM Classification, Eighth Edition) esophageal cancer (EC) are limited. Therefore, this retrospective study aimed to clarify the clinical outcomes of definitive radiotherapy (RT) or chemoradiotherapy (CRT) for cT1aN0M0 EC unsuitable for endoscopic resection and surgery. Methods: Patients with cT1aN0M0 esophageal squamous cell carcinoma who underwent definitive RT or CRT between January 2009 and December 2020 were retrospectively reviewed. The initial response, toxicities, survival rates, recurrence patterns, and salvage treatments of the patients were evaluated. Initial response was measured using the Response Evaluation Criteria in Solid Tumors guideline. Toxicity was assessed and documented following the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Survival rates from the date of initiation of treatment were measured using the Kaplan-Meier method. Results: Twenty patients treated with definitive RT or CRT were included in the study. The median follow-up duration was 55 months (range, 13-131 months). All patients achieved complete response to the initial treatment. Grade 3 acute toxicities observed esophagitis (10%), pneumonitis (5%), and leukopenia (5%). Late toxicities higher than grade 3 were not observed. The 1-, 3-, and 5-year overall and disease-specific survival rates were 100% and 100%, 83% and 100%, and 67% and 100%, respectively. No treatment-related deaths occurred. Among the 20 patients, 6 showed local recurrence and 2 showed metachronous recurrence. Seven patients underwent salvage endoscopic submucosal dissection (ESD), and one underwent argon plasma coagulation treatment. After the endoscopic treatment, no recurrences were observed. Conclusions: Definitive RT or CRT was considered an alternative initial treatment for patients with cT1aN0M0 EC who were unsuitable for endoscopic resection and surgery.

Radiologic criteria of retropharyngeal lymph node metastasis in maxillary sinus cancer.

OBJECTIVE: To determine the most appropriate radiologic criteria of metastatic retropharyngeal lymph nodes (RLNs) in patients with maxillary sinus cancer (MSC). MATERIALS AND METHODS: We retrospectively evaluated 16 consecutive patients who underwent magnetic resonance imaging (MRI) before and after the treatment of locally advanced squamous cell carcinoma of the maxillary sinus. The minimal and maximal diameters of all RLNS were recorded. RLNs were classified as metastatic on the basis of the MRI follow-up (f/u). RLNs were considered non-metastatic if stable disease continued until the final MRI f/u and metastatic in cases with different evaluations (complete response, partial response, progressive disease) determined using Response Evaluation Criteria in Solid Tumours (RECIST) ver. 1.1. The receiver operating characteristic curve (ROC) and area under the curve (AUC) were used to assess the accuracy of various criteria in the diagnosis of metastatic RLNs. RESULTS: Of the 34 RLNs in 16 cases observed on pretreatment MRI, 7 were classified as metastatic RLNs and 27 as non-metastatic RLNs. Using the radiologic criteria, metastatic RLNs tended to be diagnosed more accurately with the minimal axial diameter than with the maximal axial diameter (AUC; 0.97 vs. 0.73, p = 0.06). The most accurate size criterion of metastatic RLNs was a minimal axial diameter of 5 mm or larger, with an accuracy of 94.1% (32 of 34). CONCLUSIONS: The most appropriate radiologic criterion of metastatic RLNs in MSC is a minimal axial diameter of 5 mm or longer.

A prospective feasibility study of a 1-mm bolus for postmastectomy radiotherapy.

BACKGROUND: The optimal chest wall bolus regimen for postmastectomy radiotherapy (PMRT) remains unknown. We aimed to prospectively evaluate the use of a 1-mm-thick daily tissue-equivalent bolus in patients who received PMRT using thermoluminescent dosimeters (TLDs) and skin toxicity assessment. METHODS: Patients with a 1-mm-thick daily bolus during PMRT were prospectively enrolled at The Juntendo University Hospital. The surface dose was measured in vivo under the 1-mm-thick bolus on the chest wall. We assessed the acute skin toxicity weekly during PMRT, and 1, 2, 4, and 12 weeks after the completion of PMRT. RESULTS: A total of 19 patients aged 32-79 years old received PMRT from July 2019 to January 2020. All patients completed the protocol treatment without interruptions, and the median follow-up was 32 weeks. In vivo dosimetry analysis revealed surface doses between 77 and 113% of the prescribed dose, with a mean of 92% of the prescribed radiation dose, and a standard deviation of 7% being delivered. Grade 2 dermatitis was found in 10 patients (53%), and Grade 3 dermatitis was found in one patient (5%). All cases of Grade 2 and 3 dermatitis were improved 4 weeks after PMRT. There were no cases of Grade 4 dermatitis and no chest wall recurrences during the treatment or follow-up period. CONCLUSIONS: Results confirmed the feasibility of using a 1-mm-thick daily bolus for PMRT, exhibiting an appropriate dose buildup and acceptable skin toxicity without treatment interruptions. TRIAL REGISTRATION: The University Hospital Medical Information Network Clinical Trials Registry, UMIN000035773 . Registered 1 July 2019.

Invasion of the pterygoid plates: an indicator for regional lymph node failure in maxillary sinus cancer.

BACKGROUND: The aim of this study was to evaluate the long-term treatment results of combined superselective intraarterial chemotherapy and radiation therapy for advanced maxillary sinus cancer (MSC) and the incidence of regional lymph node failure, and to reveal the clinical and anatomical predictive factors for metastasis. METHODS: We retrospectively evaluated 55 consecutive patients with locally advanced squamous cell carcinoma of the maxillary sinus who were treated with external radiotherapy and superselective intraarterial chemotherapy. Elective nodal irradiation (ENI) was performed only in the clinical node-positive (cN+) cases and not in the clinical node-negative (cN0) cases. RESULTS: Thirty-eight patients were cN0, and 17 were cN+ at diagnosis. Regional lymph node metastases occurred in 7 of 38 patients with cN0, and 2 of 17 with cN+ during the median follow-up period of 36 months. There were more cases of high-grade (3 or 4) late adverse events in the ENI group than in the non-ENI group (13% vs. 41%, respectively; p = 0.03). In cN0 cases without ENI, invasion of the pterygoid plates (57% vs. 90%; p < 0.01) and oral cavity (35% vs. 92%, with invasion vs without invasion, respectively; p = 0.02) was significantly correlated with a low 5-year regional recurrence-free rate. CONCLUSIONS: Patients with MCS and invasion of the pterygoid plates and oral cavity can be considered appropriate candidates for ENI.

Dosimetric assessment of bolus for postmastectomy radiotherapy.

There remains wide variation in the use of chest wall boluses for postmastectomy radiotherapy, which may result from the need for 2 treatment plans with the commonly used half-time tissue-equivalent 5-mm-thick bolus to achieve a full surface dose. To establish a bolus method requiring one treatment plan, we assessed the surface dose of a thinner daily bolus for all treatment fractions and compared it against the half-time 5-mm-thick bolus. In this basic study, we specifically investigated dosage achieved when using the following: (1) the existing bolus protocol, a half-time 5-mm-thick tissue-equivalent Clearfit bolus (Fujidenolo Inc., Aichi, JP); (2) no bolus; and (3) daily 1-, 2-, and 3-mm-thick Clearfit boluses at 4 and 6 MV photons. Dosimetric measurements were then taken in an anthropomorphic phantom to study the effect of each regimen on the surface doses, and the mean surface doses of the daily thinner boluses were compared with the existing bolus protocol by the Welch 2-sample t test. The mean surface doses for the existing bolus protocol, no bolus, and daily 1-, 2-, and 3-mm-thick boluses were 68% (range, 59% to 77%), 53% (41% to 66%), 73% (60% to 83%), 77% (66% to 87%), and 82% (75% to 91%) of the prescription dose at 4 MV, respectively; the corresponding values at 6 MV were 71% (63% to 79%), 50% (39% to 60%), 72% (56% to 83%), 81% (68% to 90%), and 89% (80 to 97%) of the prescription dose. The mean surface doses were comparable between the existing bolus protocol and the 1-mm-thick daily bolus at 4 and 6 MV. In conclusion, the mean surface dose of a 1-mm-thick bolus approximate that of a half-time 5-mm-thick bolus at 4 and 6 MV. As such, we have started a prospective clinical study on the safety and efficacy of a 1-mm-thick bolus for postmastectomy radiotherapy.

Focal low-dose-rate prostate brachytherapy for low- and intermediate-risk prostate cancer.

PURPOSE: To prospectively investigate the efficacy and feasibility of focal low-dose-rate (LDR) prostate brachytherapy for low- and intermediate-risk prostate cancer. MATERIAL AND METHODS: Between October 2014 and May 2019, nineteen low- and intermediate-risk prostate cancer patients who presented with abnormality on both diffusion-weighted and T2-weighted magnetic resonance imaging (MRI) underwent focal LDR brachytherapy at our institution. Focal gross tumor volume (F-GTV) was delineated on transrectal ultrasound, based on abnormality seen on fused T2-weighted MRI. F-GTV was expanded by 5 mm, as a safety margin, to create focal clinical target volume (F-CTV). Prescribed dose to F-CTV was 145 Gy. Biochemical recurrence (BCR) was determined using Phoenix criterion (prostate specific antigen nadir + 2 ng/ml). Pre- and post-implant dosimetry data were compared using non-parametric Wilcoxon's rank sum test. Treatment-related toxicities were evaluated using common terminology criteria for adverse events. RESULTS: Mean F-CTV D90% was significantly lower in the post-implant evaluation than in intraoperative planning (p = 0.004). On post-implant dosimetry, the mean D90% for F-GTV and mean V100% for the entire prostate were 222 Gy and 35%, respectively. Median follow-up time for all patients was 31 months. BCR occurred in one patient after 23 months. Kaplan-Meier 2-year BCR-free rate was 92.9% (95% confidence interval [CI]: 79.4-100%). No patients had grade 1 or greater gastrointestinal toxicity. Three patients who were taking α-blockers to treat benign prostatic hyperplasia (present before brachytherapy), experienced no treatment-related genitourinary toxicities. Two patients suffered from temporary grade 2 urinary frequency. None of the remaining patients experienced grade 2 or higher genitourinary toxicity. CONCLUSIONS: Focal LDR prostate brachytherapy appears acceptable for MRI-based index tumors, with a low cumulative incidence of BCR. Such brachytherapy might offer a feasible minimally invasive therapeutic option for localized prostate cancer.

Safety of radiotherapy with concurrent docetaxel in older patients with esophageal cancer.

OBJECTIVES: Considering that therapeutic strategies for older adult patients with esophageal cancer (EC) remain controversial, we aimed to assess the safety of radiotherapy with concurrent docetaxel (DOC-RT) among older adult patients with EC. MATERIALS AND METHODS: Eligible patients included those aged ≥76 years who were diagnosed with esophageal squamous cell carcinoma. Patients received radiotherapy (60 Gy in 30 fractions) and concurrent docetaxel (10 mg/m2 weekly for six cycles). Survival, toxicity, and treatment completion rates were retrospectively evaluated. RESULTS: Among 84 older adult patients receiving radical radiotherapy or chemoradiotherapy, 73 receiving DOC-RT were studied. Median follow-up duration was 14 months (range, 2-101 months). The 1-, 3-, and 5-year overall survival rates were 63%, 33%, and 13%, respectively, with a median survival time of 21 months. Grade 3 acute toxicities included esophagitis (7%), esophageal fistula (3%), pneumonitis (1%), leukopenia (10%), and anemia (8%). Grade 3 late toxicities included esophageal stenosis (4%), pleural effusion (3%), pericardial effusion (1%), and pneumonitis (1%). Grade 4 and 5 toxicities were not observed. DOC-RT was discontinued due to deterioration in the general condition (6%), esophageal fistula (3%), pneumonia (1%), and pain (1%), resulting in a DOC-RT completion rate of 89% (65/73 patients). The non-completion group comprised a higher proportion of older adults (age ≥ 80 years) and undernourished [geriatric nutritional risk index (GNRI <92)] patients than the completion group. CONCLUSION: DOC-RT can be a safe regimen for older adult patients with EC. Nonetheless, old age (≥80 years) and undernourishment (GNRI <92) should be considered prior to DOC-RT administration.