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Background: In advanced head and neck cancer (HNC) patients, 50–60% experience loco-regional relapse and distant metastasis. Boron neutron capture therapy (BNCT) has shown remarkable therapeutic response in recurrent HNC, but there is still a 70% chance of local recurrence. This study aimed to identify a suitable liquid biomarker to assess patient response following BNCT. Myeloid-derived suppressor cells (MDSCs) are immune-suppressive cells that inhibit cytotoxic T cells. Circulating MDSC levels have been linked to the clinical stage and prognosis in HNSCC. Methods: Five patients with recurrent head and neck cancer underwent a treatment regimen that commenced with BNCT, followed by fractionated image-guided intensity-modulated radiotherapy (IG-IMRT). Liquid biopsy analysis via flow cytometry and tumor volume analysis by clinical imaging were conducted at three stages: before BNCT, before the first fraction of IG-IMRT, and one month after the last fraction of IG-IMRT. Results: Compared to other MDSC subtypes, monocytic MDSCs (M-MDSCs) exhibited a notable correlation with tumor volume. This strong correlation was observed at all testing time points except one month after BNCT treatment. Conclusions: This case series highlights a strong link between tumor size and circulating M-MDSC levels before BNCT and one month after the last IG-IMRT treatment in recurrent head and neck cancer patients. These results suggest that the level of circulating M-MDSCs could be a marker for monitoring tumor progression in recurrent HNC patients following radiation therapy, including BNCT. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to assess the toxicity profile and clinical outcome in patients with locally advanced cervical cancer (LACC) treated with a combination of image-guided intensity-modulated radiation therapy (IG-IMRT) and image-guided brachytherapy (IGBT). Material and methods: 25 LACC patients were recruited in this single-arm prospective study. Whole pelvis IG-IMRT was delivered (45 Gy with simultaneously integrated nodal boost of 55 Gy in 25 fractions), with concurrent weekly cisplatin (40 mg/m2). Patients received IGBT of 7 Gy each in 4 fractions to high-risk clinical target volume (HR-CTV). First fraction was done under MRI, and subsequent fractions were performed under CT guidance. Primary endpoint was acute toxicity, and secondary endpoints were 2-year loco-regional control and late toxicity. Results: The median age was 52 years, and FIGO 2018 stage distribution was IIA2, IIB, IIIB, and IIIC1 in 12%, 40%, 20%, and 28% patients, respectively. All patients received concurrent chemotherapy with median number of 5 cycles (range, 4-5 cycles). Grade 1 and 2 diarrhea, and grade 1 cystitis was reported in 4 (16%), 3 (12%), and 2 (8%) patients, respectively. Grade 1 and 2 anemia, and grade 1 and 2 dermatitis were observed in 3 (12%) and 2 (8%), and 3 (12%) and 3 (12%) patients, respectively. No patient reported grade 3-4 acute toxicity. At median follow-up of 29.5 months (range, 25-37 months), late grade 1 bladder toxicity was observed in 1 (4%) patient. Loco-regional control at 1 and 2 years were 96% and 92%, respectively. Conclusions: The combination of IG-IMRT and IGBT yielded excellent outcomes in terms of acute toxicity and loco-regional control. [ABSTRACT FROM AUTHOR]

Condensed abstract: No large-scale, well-designed randomized study with a long-term follow-up has evaluated the survival effect of pretreatment 18-fluorodeoxyglucose positron emission tomography-computed tomography (18FDG-PET-CT) on patients with stage IB-IVA cervical cancer receiving imageguided intensity-modulated radiation therapy (IG-IMRT). This is the first head-tohead propensity score-matched, nationwide population-based cohort study evaluating this survival effect. The results revealed that pretreatment 18FDGPET- CT might be associated with longer survival in patients with stage IB-IVA cervical cancer receiving radiotherapy or concurrent chemoradiotherapy, especially in the IG-IMRT era. Purpose: No large-scale, well-designed randomized study with a long-term follow-up has evaluated the survival effect of pretreatment 18-fluorodeoxyglucose positron emission tomography-computed tomography (18FDG-PET-CT) on patients with stage IB-IVA cervical cancer receiving imageguided intensity-modulated radiation therapy (IG-IMRT). Therefore, in this propensity score-matched, population-based cohort study, we investigated these survival effects. Patients and methods: We included 4167 patients with stage IB-IVA cervical cancer receiving radiotherapy (RT) or concurrent chemoradiotherapy (CCRT) through the IG-IMRT technique. The patients were categorized into two 1:2 propensity score-matched groups depending on whether they underwent pretreatment 18FDG-PET-CT, and their outcomes were compared. Results: We included 2778 and 1389 patients with cervical cancer in the nonpretreatment and pretreatment PET-CT groups, respectively. Univariable and multivariable analyses revealed an association between pretreatment PET-CT and improved survival in the patients (in the adjusted model, the adjusted hazard ratio [aHR] was 0.88; 95% confidence interval [CI], 0.80-0.97: P = 0.010). Regardless of the cancer stage (early or advanced), pretreatment PET-CT was significantly superior to nonpretreatment PET-CT in terms of all-cause death (aHR, 0.78; 95% CI, 0.60-0.92; P = 0.013 and aHR, 0.90; 95% CI, 0.81-0.99; P = 0.039 for the early [IB-IIA] and advanced stages [IIB-IVA], respectively). Conclusions: Pretreatment 18FDG-PET-CT might be associated with longer survival in patients with stage IB-IVA cervical cancer receiving RT or CCRT, especially in the era of IG-IMRT. [ABSTRACT FROM AUTHOR]

Background: To investigate the efficacy, toxicity and prognosis of image-guided intensity-modulated radiotherapy (IG-IMRT) in patients with FIGO IIIC1 cervical cancer. Methods: We retrospectively reviewed clinical records of patients with FIGO IIIC1 cervical cancer treated with definitive IG-IMRT in our institute from January 2008 to December 2017. A dose of 50.4Gy in 28 fractions was prescribed to at least 95% of PCTV, the positive pelvic lymph nodes received a dose of 56-61.6Gy in 28 fractions with simultaneous integrated boost (SIB). Weekly cone beam compute tomography (CBCT) and daily megavoltage CT (MVCT) was performed before treatment. Both 2D brachytherapy and 3D brachytherapy were allowed in our study. Weekly Cisplatin (30-40mg/m2) was the first line regimen for concurrent chemotherapy. Overall survival (OS), disease free survival (DFS), local control (LC) and local regional control (LRC) was calculated with Kaplan-Meier method. Cox proportional hazard model was used to perform univariate and multivariate analyses. Results: A total of 502 patients were enrolled in this study. The median follow-up duration was 42.1 months (range: 2.3-137.3 months). The 3-year and 5-year estimated OS, DFS, LC, LRC were 81.7% and 75.5%, 71.4% and 68.6%, 89.9% and 89.9%, 86.1% and 84.3%, respectively. The incidences of chronic grade 3 or greater gastrointestinal and genitourinary toxicities were 2.7 % and 0.8%, respectively. Pelvic lymph nodes recurrence occurred in 21 patients (4.2%). Advanced T stage was identified as adverse factor for OS and LC. More positive lymph nodes (≥2) were associated with worse OS, DFS and LRC. The cycles of concurrent chemotherapy significantly affected OS, DFS and LRC. Conclusion: For patients with FIGO IIIC1 cervical cancer, IG-IMRT was well tolerated with excellent survivals. T stage and number of positive lymph nodes significantly influenced the survivals indicating the heterogeneity of stage IIIC1 cervical cancer patients. Adequate cycles of chemotherapy (≥4 cycles) was of great value for this group of patients., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Condensed Abstract: No large-scale, well-designed randomized study with a long-term follow-up has evaluated the survival effect of pretreatment 18-fluorodeoxyglucose positron emission tomography-computed tomography ( 18 FDG-PET-CT) on patients with stage IB-IVA cervical cancer receiving image-guided intensity-modulated radiation therapy (IG-IMRT). This is the first head-to-head propensity score-matched, nationwide population-based cohort study evaluating this survival effect. The results revealed that pretreatment 18 FDG-PET-CT might be associated with longer survival in patients with stage IB-IVA cervical cancer receiving radiotherapy or concurrent chemoradiotherapy, especially in the IG-IMRT era., Purpose: No large-scale, well-designed randomized study with a long-term follow-up has evaluated the survival effect of pretreatment 18-fluorodeoxyglucose positron emission tomography-computed tomography ( 18 FDG-PET-CT) on patients with stage IB-IVA cervical cancer receiving image-guided intensity-modulated radiation therapy (IG-IMRT). Therefore, in this propensity score-matched, population-based cohort study, we investigated these survival effects., Patients and Methods: We included 4167 patients with stage IB-IVA cervical cancer receiving radiotherapy (RT) or concurrent chemoradiotherapy (CCRT) through the IG-IMRT technique. The patients were categorized into two 1:2 propensity score-matched groups depending on whether they underwent pretreatment 18 FDG-PET-CT, and their outcomes were compared., Results: We included 2778 and 1389 patients with cervical cancer in the nonpretreatment and pretreatment PET-CT groups, respectively. Univariable and multivariable analyses revealed an association between pretreatment PET-CT and improved survival in the patients (in the adjusted model, the adjusted hazard ratio [aHR] was 0.88; 95% confidence interval [CI], 0.80-0.97: P = 0.010). Regardless of the cancer stage (early or advanced), pretreatment PET-CT was significantly superior to nonpretreatment PET-CT in terms of all-cause death (aHR, 0.78; 95% CI, 0.60-0.92; P = 0.013 and aHR, 0.90; 95% CI, 0.81-0.99; P = 0.039 for the early [IB-IIA] and advanced stages [IIB-IVA], respectively)., Conclusions: Pretreatment 18 FDG-PET-CT might be associated with longer survival in patients with stage IB-IVA cervical cancer receiving RT or CCRT, especially in the era of IG-IMRT., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Su, Chen, Chen, Shia and Wu.)

Purpose: Re-irradiation (re-RT) is considered a treatment option for inoperable locoregionally recurrent head and neck cancer (HNC) after prior radiotherapy. We evaluated the efficacy and safety of re-RT using Helical Tomotherapy as image-guided intensity-modulated radiotherapy in recurrent HNC. Materials and Methods: Patients diagnosed with recurrent HNC and received re-RT were retrospectively reviewed. Primary endpoint was overall survival (OS) and secondary endpoints were locoregional control and toxicities. Results: The median follow-up period of total 9 patients was 18.7 months (range, 4.1 to 76 months) and that of 3 alive patients was 49 months (range, 47 to 76 months). Median dose of first radiotherapy and re-RT was 64.8 and 47.5 Gy10. Median cumulative dose of the two courses of radiotherapy was 116.3 Gy10 (range, 91.8 to 128.9 Gy10) while the median interval between the two courses of radiation was 25 months (range, 4 to 137 months). The response rate after re-RT of the evaluated 8 patients was 75% (complete response, 4; partial response, 2). Median locoregional relapse-free survival after re-RT was 11.9 months (range, 3.4 to 75.1 months) and 5 patients eventually presented with treatment failure (in-field failure, 2; in- and out-field failure, 2; out-field failure, 1). Median OS of the 8 patients was 20.3 months (range, 4.1 to 75.1 months). One- and two-year OS rates were 62.5% and 50%, respectively. Grade 3 leucopenia developed in one patient as acute toxicity, and grade 2 osteonecrosis and trismus as chronic toxicity in another patient. Conclusion: Re-RT using Helical Tomotherapy for previously irradiated patients with unresectable locoregionally recurrent HNC may be a feasible treatment option with long-term survival and acceptable toxicities. [ABSTRACT FROM AUTHOR]

Abstract: Use of image guided (IG) intensity modulated radiotherapy (IMRT) is increasing, and helical tomotherapy provides an effective, integrated solution. Practical experience of implementation, shared at a recent UK TomoTherapy Users' meeting, may help centres introducing these techniques using TomoTherapy or other platforms. Seven centres participated, with data shared from 6, varying from 2500 - 4800 new patients per year. Case selection of patients “most likely” to benefit from IG-IMRT was managed in all centres by multi-professional groups comprising clinical oncologists, physicists, treatment planners and radiographers. Radical treatments ranged from 94% to 100%. The proportions of tumour types varied substantially: head and neck: range 0%–100% (mean of centres 50%), prostate: 3%–96% (mean of centres 28%). Head and neck cases were considered most likely to benefit from IMRT, prostate cases from IGRT, or IG-IMRT if pelvic nodes were being treated. IMRT was also selected for complex target volumes, to avoid field junctions, for technical treatment difficulties, and retreatments. Across the centres, every patient was imaged every day, with positional correction before treatment. In one centre, for prostate patients including pelvic treatment, the pelvis was also imaged weekly. All centres had designed a ‘ramp up’ of patient numbers, which was similar in 5. One centre, treating 96% prostate patients, started with 3 and increased to 36 patients per day within 3 months. The variation in case mix implies wide applicability of IG-IMRT. Daily on-line IGRT with IMRT can be routinely implemented into busy departments. [Copyright &y& Elsevier]

The influence of androgen deprivation therapy (ADT) on other-cause of mortality (OCM) was investigated in patients with localized prostate cancer treated with modern high-dose radiotherapy. A retrospective review was conducted on 1125 patients with localized prostate cancer treated with high-dose radiotherapy, including image-guided, intensity-modulated radiotherapy or brachytherapy with a median follow-up of 80.7 months. Overall survival rate was no different between ADT (+) and ADT (−) group in high-, intermediate-, and low-risk groups. OCM was found in 71 patients, consisting of 4% (10/258) in the ADT (−) group and 7% (61/858) in the ADT (+) group (p = 0.0422). The 10-year OCM-free survival rate (OCMFS), if divided by the duration of ADT (ADT naïve (ADT (−)), ADT <2-year, and ADT ≥2-year groups), showed statistical significance, and was 90.7%, 88.2%, and 78.6% (p = 0.0039) for the ADT (−), ADT <2-year, and ADT ≥2-year groups, respectively. In patients aged ≥75 years, 10-year OCMFS for ADT (−), ADT <2-, and ADT ≥2-year groups was 93.5% (at 115.6 months), 85.6%, and 60.7% (p = 0.0189), respectively, whereas it was 90.7%, 89.9%, and 89.0% (p = 0.4716), respectively, in their younger counterparts. In localized prostate cancer patients, treatment with longer ADT for ≥2 years potentially increases the risk of OCM, especially in patients aged ≥75 years. [ABSTRACT FROM AUTHOR]

We compared radiotherapy outcomes between 241 elderly patients aged ≥75 years and 867 younger controls (age <75 years) with clinically localized prostate cancer. The elderly group showed an equivalent actuarial seven-year biochemical failure-free survival rate (7y-bNED) (94.9%) to the younger control group (96.4%, p = 0.593). The incidence of late genitourinary (GU) and gastrointestinal (GI) toxicities grade ≥2 was also similar between the elderly and younger cohorts, while no grade ≥4 adverse events occurred. We also examined the role of brachytherapy (BT) in the elderly group, in comparison with image-guided intensity-modulated radiotherapy (IG-IMRT). BT showed superior 7y-bNED (94.1%) than IG-IMRT (84.6%, p = 0.0183) in elderly patients, which was 100% (100% for BT and 100% for IG-IMRT, p > 0.999) for the low-risk group, 94.6% (92.8% and 100%, p = 0.203) for the intermediate-risk group, and 80.5% (91.2% and 73.6%, p = 0.0195) for the high-risk group. BT showed higher GU toxicity and equivalent GI toxicity to IG-IMRT. In conclusion, elderly patients showed bNED and toxicity that were equivalent to those observed in younger controls, and BT is a plausible option also for healthy elderly with potential to improve bNED, with higher but acceptable GU toxicity. [ABSTRACT FROM AUTHOR]

Aim: To investigate the correlation between frequency of action level of interfractional rectal displacement requiring repeated precaution in patients with prostate cancer and late toxicity from image-guided intensity-modulated radiation therapy (IG-IMRT) using helical tomotherapy., Patients and Methods: We examined 264 patients who underwent IG-IMRT during 2007-2011. Megavoltage computed tomographic (MVCT) images were acquired before radiation therapy and was examined with soft-tissue matching by comparing treatment planning images within 9,345 fractions. Displacement of the anterior rectal region larger than 5 mm, requiring repeated precaution, was defined as the level of rectal displacement requiring action (ARD)., Results: ARD was identified in 815 (7.7%) out of 9,345 fractions and at least once in 82% (216/264) of patients. The highest incidence of ARD (11%) was found during the initial week of treatment (first five and next five fractions), after which the incidence decreased to 6% (p<0.0001). Patients with lean body (lower body mass index (BMI) tended to have a higher incidence of ARD. We identified 16 (6%) cases of gastrointestinal toxicity and 12 (4.5%) genitourinary toxicities as a late adverse reaction (3 months or later after IG-IMRT). There was no correlation between ARD and late toxicity. Prostate-specific antigen (PSA) control was also similar (p=0.12) between those with ARD (96% at 5 year) and those without ARD (88%)., Conclusion: ARD occurred predominantly in lean patients, during the initial week of treatment and became less likely over time. ARD was not correlated to late toxicity and PSA control, therefore, IG-IMRT technique was able to adequately control error due to interfractional prostate and rectal motion., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: Re-irradiation (re-RT) is considered a treatment option for inoperable locoregionally recurrent head and neck cancer (HNC) after prior radiotherapy. We evaluated the efficacy and safety of re-RT using Helical Tomotherapy as image-guided intensity-modulated radiotherapy in recurrent HNC., Materials and Methods: Patients diagnosed with recurrent HNC and received re-RT were retrospectively reviewed. Primary endpoint was overall survival (OS) and secondary endpoints were locoregional control and toxicities., Results: The median follow-up period of total 9 patients was 18.7 months (range, 4.1 to 76 months) and that of 3 alive patients was 49 months (range, 47 to 76 months). Median dose of first radiotherapy and re-RT was 64.8 and 47.5 Gy10. Median cumulative dose of the two courses of radiotherapy was 116.3 Gy10 (range, 91.8 to 128.9 Gy10) while the median interval between the two courses of radiation was 25 months (range, 4 to 137 months). The response rate after re-RT of the evaluated 8 patients was 75% (complete response, 4; partial response, 2). Median locoregional relapse-free survival after re-RT was 11.9 months (range, 3.4 to 75.1 months) and 5 patients eventually presented with treatment failure (in-field failure, 2; in- and out-field failure, 2; out-field failure, 1). Median OS of the 8 patients was 20.3 months (range, 4.1 to 75.1 months). One- and two-year OS rates were 62.5% and 50%, respectively. Grade 3 leucopenia developed in one patient as acute toxicity, and grade 2 osteonecrosis and trismus as chronic toxicity in another patient., Conclusion: Re-RT using Helical Tomotherapy for previously irradiated patients with unresectable locoregionally recurrent HNC may be a feasible treatment option with long-term survival and acceptable toxicities.