Treatment Related Acute Toxicities Between Treatment with 3D-CRT and IMRT in Localised Prostate Cancer.

OBJECTIVE:  To compare the acute toxicities of two radiation treatment techniques, intensity modulated radiation therapy (IMRT), and 3-dimensional conformal radiation therapy (3D-CRT) in localised prostate adenocarcinoma. STUDY DESIGN: Descriptive study. Place and Duration of the Study: Department of Oncology, Dr. Ziauddin Hospital, Karachi, Pakistan, from July 2016 to June 2022. METHODOLOGY: Patients with localised prostate adenocarcinoma who underwent treatment using two different advanced radiotherapy techniques i.e., IMRT and 3D-CRT were recruited during the study period. They were followed up for six months for acute gastrointestinal (GI) and genitourinary (GU) adverse events (acute toxicities) related to both treatment modalities according to Modified radiation therapy oncology group (RTOG) criteria. The acute toxicities were assessed at the 2nd, 4th, and 6th week during treatment and at the 3rd and 6th month after treatment. RESULTS:  There were 78 patients, with 39 patients in each group. The mean age was 68 ± 10 years in the 3D-CRT and 68 ± 07 years in the IMRT group. Patients in the IMRT group exhibited markedly lower treatment-related acute GI and GU effects at the end of 4th and 6th weeks for anorectal pain (p = 0.04) and (p = 0.01) and burning micturition (p = 0.003) and (p = 0.01), respectively. Furthermore, at 3 months anorectal pain (p = 0.02), loose stools (p = 0.005), and burning micturition (p = 0.01) were present and at 6 months anorectal pain was (p = 0.01) still present. CONCLUSION: Radiation therapy modalities 3D-CRT and IMRT both showed acceptable toxicity profile in the management of localised prostate cancer, while IMRT group exhibited significantly lower treatment-related acute GI and GU effects. KEY WORDS: 3D-CRT (3-Dimensional Conformal Radiation Therapy), IMRT (Intensity-Modulated Radiation Therapy), Radiation toxicity.

The impact of bolus on clinical outcomes for post-mastectomy breast cancer patients treated with IMRT: data from China.

PURPOSE: This study aims to investigate the effects of chest wall bolus in intensity-modulated radiotherapy (IMRT) technology on clinical outcomes for post-mastectomy breast cancer patients. MATERIALS AND METHODS: This retrospective study included patients with invasive carcinoma ((y)pT0-4, (y)pN0-3) who received photon IMRT after mastectomy at the Affiliated Hospital of Qingdao University from 2014 to 2019. The patients were divided into two groups based on whether they received daily bolus application or not, and the baseline characteristics were matched using propensity score matching (PSM). Cumulative incidence (CI) of local recurrence (LR), locoregional recurrence (LRR), overall survival (OS) and disease-free survival (DFS) were evaluated with a log-rank test. Acute skin toxicity and late radiation pneumonia was analyzed using chi-square test. RESULTS: A total of 529 patients were included in this study, among whom 254 (48%) patients received bolus application. The median follow-up time was 60 months. After matching, 175 well-paired patients were selected. The adjusted 5-year outcomes (95% confidence interval) in patients treated with and without bolus were, respectively: CI of LR 2.42% (0.04-4.74) versus 2.38% (0.05-4.65), CI of LRR 2.42% (0.04-4.74) versus 3.59% (0.73-6.37), DFS 88.12% (83.35-93.18) versus 84.69% (79.42-90.30), OS 94.21% (90.79-97.76) versus 95.86% (92.91-98.91). No correlation between bolus application and skin toxicity (P = 0.555) and late pneumonia (P = 0.333) was observed. CONCLUSIONS: The study revealed a low recurrence rate using IMRT technology. The daily used 5 mm chest wall bolus was not associated with improved clinical outcomes.

Comparison of Acute Toxicities, Overall Treatment Time and Quality of Life in Head and Neck Cancer Patients Treated with IMRT and Helical Tomotherapy.

INTRODUCTION: Technical innovations in radiation therapy treatment planning and delivery over the last two decades have changed the practice of radiation therapy dramatically. The benefit of improved dose homogeneity and better sparing of critical structures in helical tomotherapy compared with conventional linac-based IMRT has been reported. This study was conducted to compare acute toxicities (skin, mucous membrane, salivary gland and hematological) during treatment and overall treatment time in Head and Neck Cancer patients treated with IMRT and Helical Tomotherapy and to assess the quality of life of patients during treatment between two groups. MATERIALS AND METHODS: The study involved thirty patients with histologically proven Squamous cell carcinomas of Head and Neck. They were treated with concurrent chemoradiotherapy, to a dose of 60-70 Gray in 30-35 fractions. The study consists of 2 arms which are standard IMRT and Tomotherapy arm. Fifteen consecutive patients were treated under IMRT and 15 patients were treated under Helical tomotherapy, along with concurrent chemotherapy. After completion of planning, plans were evaluated and dose to the targets, organs at risk were tabulated. Patients were assessed weekly for acute toxicities (skin reactions, mucositis, xerostomia, haematological toxicities) during the course of the treatment as per RTOG criteria. Quality of life of patients were assessed using FACT/ NCCN HNSI questionnaire in local language at day 1, day 21 and at completion of radiotherapy. RESULTS: Grade 2-3 skin reactions, mucositis, anemia, leukopenia and thrombocytopenia were predominant in both arms. Treatment time from start of radiotherapy to completion of radiotherapy varied from 39 days to 68 days. Majority of patients completed radiotherapy within 50-56 days. Mean quality of life score did not show much difference between IMRT and tomotherapy arms. CONCLUSION: The study did not show any statistically significant difference in overall treatment time, acute toxicities- skin reactions, xerostomia, mucositis& hematological toxicities and quality of life of patients during radiotherapy between IMRT and Helical Tomotherapy. Dosimetric benefits of Tomotherapy over IMRT do not translate into clinical benefit in terms of reduced acute toxicities, lesser overall treatment time and better quality of life of patients. KEY WORDS: Head and Neck Carcinoma, IMRT, Tomotherapy, RTOG, toxicity, FACT/ NCCN HNSI, quality of life.

Osteonecrosis of the jaw after radiation followed by bevacizumab.

Osteonecrosis of the jaw is a recognized complication associated with bevacizumab. Here, we present a patient with squamous cell carcinoma of the tonsil who experienced minimal skin fibrosis following intensity-modulated radiation therapy. Subsequently, the patient developed rectal adenocarcinoma and encountered osteonecrosis of the jaw after receiving two cycles of bevacizumab. Close monitoring, accompanied by thorough examination to detect early signs of osteonecrosis of the jaw, should be considered for patients who have undergone radiation therapy in the head and neck region and are receiving bevacizumab or other medications known to be associated with osteonecrosis of the jaw.

[Concurrent simultaneous integrated boost radiotherapy and cetuximab in head and neck squamous cell cancer patients: is it feasible in daily clinical practice?] / Radioterapia a intensità modulata con boost simultaneo più cetuximab in pazienti con carcinoma a cellule squamose in stadio localmente avanzato del distretto testa collo: è fattibile nella pratica clinica quotidiana?

INTRODUCTION AND AIM: Locally advanced head and neck squamous cell carcinoma (LA-Hnscc) is a true therapeutical challenge in the modern era and the scientific community is trying to face this challenge with new therapeutical strategies, including combinations of monoclonal antibodies and radiation therapy. The aim of this study is to evaluate clinical outcomes in LA-Hnscc patients unfit to receive platinum-based chemotherapy, treated with concurrent simultaneous integrated boost-intensity modulated radiotherapy (Sib-Imrt) + cetuximab (Ctx) in daily clinical practice. METHODS: LA-Hnscc patients not included in other prospective studies treated in 4 Italian radiotherapy units (2 Messina, 1 Rome, and 1 Lecce) using Sib-Imrt and Ctx were included in this study. Acute and late toxicities and overall survival (OS) have been evaluated. RESULTS: Data regarding 27 patients with squamous tumour were collected and reviewed. The primary tumour sites were oropharynx in 14 patients (51.9%), oral cavity in 7 (25.9%), larynx in 3 (11%) and other sites in 3(11%). There were 20 (74%) patients had stage IV (16 IVa and 4 IVb). Complete remission was observed in 18 patients (66.7%), a partial remission in 4 (14.8%) whilst 4 had a progression disease (14.8%). After 3 year of follow-up 7/27 patients were deaths. The OS was 95.5%, 62.5% and 52.9% respectively at 1,2 and 3 years. Acute toxicities were observed in all treated patients (mucositis, dermatitis and dysphagia) while 66.7% of patients developed late toxicities. All observed toxicities were grade 1 to 3 and just 1 patient developed a G4 toxicity. CONCLUSION: The concurrent bio-radiotherapy of Sib-Imrt and cetuximab is feasible in real-life daily clinical practice for LA-Hnscc patients unfit for platinum-based chemoradiotherapy.

Long-term follow-up of protective effects on salivary and swallowing structures and improvement of late xerostomia and dysphagia by level IIb optimisation in clinical target volume of nasopharyngeal carcinoma.

BACKGROUND: This study aimed to assess the long-term effect of level IIb clinical target volume (CTV) optimisation on survival, xerostomia, and dysphagia in patients with nasopharyngeal carcinoma (NPC). METHODS: Clinical data of 415 patients with NPC treated with intensity-modulated radiotherapy between December 2014 and October 2018 were retrospectively analysed. The patients were categorised into modified and comparison groups. Late xerostomia and dysphagia were evaluated using Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer scoring. Survival analysis was performed using the Kaplan-Meier method. Differences in late toxicity and dose parameters between both groups were compared. Prognostic factors for survival and late toxicity were assessed using regression analyses. RESULTS: Patients in the modified group developed late xerostomia and dysphagia less frequently than those in the comparison group did (P < 0.001). The mean dose (Dmean) and V26 of parotid glands; Dmean and V39 of submandibular glands; and Dmean of sublingual glands, oral cavity, larynx, and superior, middle, and lower pharyngeal constrictor muscles were lower in the modified group than those in the comparison group (all P < 0.001). Both groups had no significant differences in overall, local recurrence-free, distant metastasis-free, or progression-free survival. The Dmean of the parotid and sublingual glands was a risk factor for xerostomia. The Dmean of the parotid and sublingual glands and middle pharyngeal constrictor muscle was a risk factor for dysphagia. CONCLUSIONS: Level IIb optimisation in NPC patients who meet certain criteria specially the exclusion of positive retropharyngeal nodes treated with intensity-modulated radiotherapy has the potential to better protect the salivary and swallowing structures, decreasing the development of late radiation-induced xerostomia and dysphagia while maintaining long-term survival.

Sparing Swallowing-Related Structures Reduces Post-Radiotherapy Dysphagia in Oropharyngeal Cancer.

OBJECTIVE: To identify swallowing-related structures (SRSs) predicting post-radiotherapy dysphagia in oropharyngeal carcinoma patients. MATERIAL AND METHODS: Between September 2020 and October 2022, oropharyngeal cancer patients who had completed radiotherapy at least one year before without recurrence or residuals were selected. They underwent flexible endoscopic evaluation of swallowing (FEES) assessments and dysphagia grading. The mean radiation doses delivered to their SRSs were recalculated. The correlation between radiation doses to each SRS and FEES scores was analysed. RESULTS: Twenty-nine participants, aged 51-73 years, were enrolled. Six patients had received two-dimensional radiotherapy, eight had undergone three-dimensional conformal radiotherapy, and fifteen had received intensity-modulated radiation therapy. Radiation doses to the inferior pharyngeal constrictor, cricopharyngeus and glottic larynx significantly predicted dysphagia for both semisolids (p = 0.023, 0.030 and 0.001) and liquid diets (p = 0.021, 0.013 and 0.002). The esophageal inlet significantly predicted swallowing outcomes for only the liquid diet (p = 0.007). CONCLUSIONS: This study supports that SRS-sparing during radiotherapy for oropharyngeal cancers improves swallowing outcomes.

LymphoDose: a lymphocyte dose estimation framework-application to brain radiotherapy.

Objective. Severe radiation-induced lymphopenia occurs in 40% of patients treated for primary brain tumors and is an independent risk factor of poor survival outcomes. We developed anin-silicoframework that estimates the radiation doses received by lymphocytes during volumetric modulated arc therapy brain irradiation.Approach. We implemented a simulation consisting of two interconnected compartmental models describing the slow recirculation of lymphocytes between lymphoid organs (M1) and the bloodstream (M2). We used dosimetry data from 33 patients treated with chemo-radiation for glioblastoma to compare three cases of the model, corresponding to different physical and biological scenarios: (H1) lymphocytes circulation only in the bloodstream i.e. circulation inM2only; (H2) lymphocytes recirculation between lymphoid organs i.e. circulation inM1andM2interconnected; (H3) lymphocytes recirculation between lymphoid organs and deep-learning computed out-of-field (OOF) dose to head and neck (H&N) lymphoid structures. A sensitivity analysis of the model's parameters was also performed.Main results. For H1, H2 and H3 cases respectively, the irradiated fraction of lymphocytes was 99.8 ± 0.7%, 40.4 ± 10.2% et 97.6 ± 2.5%, and the average dose to irradiated pool was 309.9 ± 74.7 mGy, 52.6 ± 21.1 mGy and 265.6 ± 48.5 mGy. The recirculation process considered in the H2 case implied that irradiated lymphocytes were irradiated in the field only 1.58 ± 0.91 times on average after treatment. The OOF irradiation of H&N lymphoid structures considered in H3 was an important contribution to lymphocytes dose. In all cases, the estimated doses are low compared with lymphocytes radiosensitivity, and other mechanisms could explain high prevalence of RIL in patients with brain tumors.Significance. Our framework is the first to take into account OOF doses and recirculation in lymphocyte dose assessment during brain irradiation. Our results demonstrate the need to clarify the indirect effects of irradiation on lymphopenia, in order to potentiate the combination of radio-immunotherapy or the abscopal effect.

High-tailored Anal Canal Radiotherapy (HIT-ART): Outcomes of a 10-Year Single Center Clinical Experience.

BACKGROUND/AIM: The current standard for anal cancer treatment is essentially a 'one size fits all' approach where the dose of radiotherapy is similar whether the tumor is very small or very large. Trials are ongoing to evaluate dose de-escalation or escalation in localized disease depending on tumor size. The aim of the study was to assess results of a personalized approach involving dose stratification by stage and boost dose adjusted according to tumor early response. PATIENTS AND METHODS: We retrospectively reviewed squamous cell anal cancer (SCAC) patients treated between 2011 and 2021 by long-course intensity-modulated radiotherapy (IMRT) and concomitant chemotherapy (CT); a sequential boost could be administered by IMRT or interventional radiotherapy (IRT) to obtain a total equivalent dose in 2 Gy (EQD2) of 54-60 Gy. RESULTS: We analyzed 110 patients (61% T3-4 stage, 71% node-positive). A total of 68.2% of patients received a sequential boost, mainly by IRT; median total EQD2 to primary site was 59.3 Gy. Acute ≥G3 toxicity rate was 36.4%. Median follow-up (FUP) was 35.4 months. A total of 83% of patients achieved clinical complete response (cCR); locoregional recurrence (LRR) occurred in 20.9% and distant metastases in 6.4% of cases. A total of 12.7% patients underwent salvage surgery. A total of 25.5% of patients reported ≥G2 and 4.5% ≥G3 late toxicity. The estimated 3-year overall survival, disease-free survival and colostomy-free survival were 92%, 72% and 84% respectively; 3-year-LRR was 22%. Nodal stage was associated with poorer cCR probability and higher LRR (p<0.05). CONCLUSION: Our results on a large cohort of patients with locally advanced SCAC and long FUP time confirmed the efficacy of IMRT; high local control and manageable toxicity also suggest IRT as a promising method in treatment personalization.

Could nutrition status predict fatigue one week before in patients with nasopharynx cancer undergoing radiotherapy?

BACKGROUND: Patients with nasopharyngeal carcinoma (NPC) undergoing radiotherapy experience significant fatigue, which is frequently underestimated due to the lack of objective indicators for its evaluation. This study aimed to explore the longitudinal association between fatigue and nutrition status 1 week in advance. METHODS: From January 2021 to June 2022, a total of 105 NPC patients who received intensity-modulated radiation therapy were enrolled in the observational longitudinal study. The significant outcomes, including the Piper Fatigue Scale-12 (PFS-12), the Scored Patient-Generated Subjective Global Assessment (PG-SGA), four body composition indices, and the Hospital Anxiety and Depression Scale (HADS), were assessed weekly from pre-treatment until the completion of radiotherapy (T0-T7) to explore their relationship. RESULTS: The trajectories of PFS-12 and all dimensions for 105 participants reached a peak during the fifth week. Sensory fatigue consistently received the highest scores (T0 = 1.60 ± 2.20, T5 = 6.15 ± 1.57), whereas behavior fatigue exhibited the fastest increase over time (T0 = 1.11 ± 1.86, T5 = 5.47 ± 1.70). Higher PG-SGA scores were found to be weakly explainable for aggravating fatigue (ß = 0.02 ~ 0.04). Unlike generalized additive mixed models, marginal structural models (MSM) produced larger effect values (ß = 0.12 ~ 0.21). Additionally, body composition indices showed weakly negative relationships with fatigue in MSMs one week in advance. CONCLUSIONS: The PG-SGA may be a more accurate predictor of future-week fatigue than individual body composition indicators, particularly when HADS is controlled for as a time-dependent confounder.

Reducing Salivary Toxicity with Adaptive Radiotherapy (ReSTART): A Randomized Controlled Trial Comparing Conventional IMRT to Adaptive IMRT in Head and Neck Squamous Cell Carcinomas.

BACKGROUND: The utility of Adaptive Radiotherapy (ART) in Head and Neck Squamous Cell Carcinoma (HNSCC) remains to be ascertained. While multiple retrospective and single-arm prospective studies have demonstrated its efficacy in decreasing parotid doses and reducing xerostomia, adequate randomized evidence is lacking. METHODS AND ANALYSIS: ReSTART (Reducing Salivary Toxicity with Adaptive Radiotherapy) is an ongoing phase III randomized trial of patients with previously untreated, locally advanced HNSCC of the oropharynx, larynx, and hypopharynx. Patients are randomized in a 1:1 ratio to the standard Intensity Modulated Radiotherapy (IMRT) arm {Planning Target Volume (PTV) margin 5 mm} vs. Adaptive Radiotherapy arm (standard IMRT with a PTV margin 3 mm, two planned adaptive planning at 10th and 20th fractions). The stratification factors include the primary site and nodal stage. The RT dose prescribed is 66Gy in 30 fractions for high-risk PTV and 54Gy in 30 fractions for low-risk PTV over six weeks, along with concurrent chemotherapy. The primary endpoint is to compare salivary toxicity between arms using salivary scintigraphy 12 months' post-radiation. To detect a 25% improvement in the primary endpoint at 12 months in the ART arm with a two-sided 5% alpha value and a power of 80% (and 10% attrition ratio), a sample size of 130 patients is required (65 patients in each arm). The secondary endpoints include acute and late toxicities, locoregional control, disease-free survival, overall survival, quality of life, and xerostomia scores between the two arms. DISCUSSION: The ReSTART trial aims to answer an important question in Radiation Therapy for HNSCC, particularly in a resource-limited setting. The uniqueness of this trial, compared to other ongoing randomized trials, includes the PTV margins and the xerostomia assessment by scintigraphy at 12 months as the primary endpoint.

A Japanese multi-institutional phase II study of moderate hypofractionated intensity-modulated radiotherapy with image-guided technique for prostate cancer.

BACKGROUND: The aim of this multi-institutional phase II study was to confirm the safety and the potential efficacy of moderately hypofractionated intensity-modulated radiotherapy (IMRT) with prostate-based image-guidance for Japanese patients. METHODS: Patients with low- or intermediate-risk localized prostate cancer were eligible. Patients with a part of high risk (having only one of the following factors, cT3a, 20 < PSA ≤ 30, or GS = 8 or 9) were also included. Hypofractionated IMRT using daily image-guided technique with prostate matching was performed with a total dose of 70 Gy in 28 fractions. Neoadjuvant hormonal therapy for 4-8 months was mandatory for patients with intermediate or high-risk prostate cancer. RESULTS: From 20 institutions, 134 patients enrolled. The median follow-up was 5.16 years (range, 1.43-6.47 years). The number of patients with low, intermediate, and high-risk prostate cancer was 20, 80, and 34, respectively. The 5-year overall, biochemical failure-free, and clinical failure-free survival was 94.5%, 96.0%, and 99.2%, respectively. The 5-year biochemical failure-free survival for patients with low-, intermediate-, and high-risk disease was 94.1%, 97.4%, and 93.9%, respectively. The incidences of grade 2 gastrointestinal (GI) and genitourinary (GU) late toxicities at 5 years were 5.3% and 5.3%, respectively. There are no acute or late toxicities ≥ grade 3. Of 124 patients who were followed for up to 5 years, the grade 2 late GU or GI toxicities were 10.5% (90% confidence intervals, 6.3-16.2%, p = 0.0958). CONCLUSION: The safety and efficacy of moderately hypofractionated IMRT with prostate-based image-guidance was confirmed among Japanese patients with prostate cancer.

Dosimetric evaluation of different planning strategies for hypofractionated whole-breast irradiation technique.

Purpose.The dose hotspot areas in hypofractionated whole-breast irradiation (WBI) greatly increase the risk of acute skin toxicity because of the anatomical peculiarities of the breast. In this study, we presented several novel planning strategies that integrate multiple sub-planning target volumes (sub-PTVs), field secondary placement, and RapidPlan models for right-sided hypofractionated WBI.Methods.A total of 35 cases of WBI with a dose of 42.5 Gy for PTVs using tangential intensity-modulated radiotherapy (IMRT) were selected. Both PTVs were planned for simultaneous treatment using the original manual multiple sub-PTV plan (OMMP) and the original manual single-PTV plan (OMSP). The manual field secondary placement multiple sub-PTV plan (m-FSMP) with multiple objects on the original PTV and the manual field secondary placement single-objective plan (m-FSSP) were initially planned, which were distribution-based of V105 (volume receiving 105% of the prescription dose). In addition, two RapidPlan-based plans were developed, including the RapidPlan-based multiple sub-PTVs plan (r-FSMP) and the RapidPlan-based single-PTV plan (r-FSSP). Dosimetric parameters of the plans were compared, and V105 was evaluated using multivariate analysis to determine how it was related to the volume of PTV and the interval of lateral beam angles (ILBA).Results.The lowest mean V105 (5.64 ± 6.5%) of PTV was observed in m-FSMP compared to other manual plans. Upon validation, r-FSSP demonstrated superior dosimetric quality for OAR compared to the two other manual planning methods, except for V5(the volume of ipsilateral lung receiving 5 Gy) of the ipsilateral lung. While r-FSMP showed no significant difference (p = 0.06) compared to r-FSSP, it achieved the lowest V105 value (4.3 ± 4.5%), albeit with a slight increase in the dose to some OARs. Multivariate GEE linear regression showed that V105 is significantly correlated with target volume and ILBA.Conclusions.m-FSMP and r-FSMP can substantially enhance the homogeneity index (HI) and reduce V105, thereby minimizing the risk of acute skin toxicities, even though there may be a slight dose compromise for certain OARs.

The influence of Gleason score ≤ 6 histology on the outcome of high-risk localized prostate cancer after modern radiotherapy.

We aimed to retrospectively review outcomes in patients with high-risk prostate cancer and a Gleason score ≤ 6 following modern radiotherapy. We analyzed the outcomes of 1374 patients who had undergone modern radiotherapy, comprising a high-risk low grade [HRLG] group (Gleason score ≤ 6; n = 94) and a high-risk high grade [HRHG] group (Gleason score ≥ 7, n = 1125). We included 955 patients who received brachytherapy with or without external beam radio-therapy (EBRT) and 264 who received modern EBRT (intensity-modulated radiotherapy [IMRT] or stereotactic body radiotherapy [SBRT]). At a median follow-up of 60 (2-177) months, actuarial 5-year biochemical failure-free survival rates were 97.8 and 91.8% (p = 0.017), respectively. The frequency of clinical failure in the HRLG group was less than that in the HRHG group (0% vs 5.4%, p = 0.012). The HRLG group had a better 5-year distant metastasis-free survival than the HRHG group (100% vs 96.0%, p = 0.035). As the HRLG group exhibited no clinical failure and better outcomes than the HRHG group, the HRLG group might potentially be classified as a lower-risk group.

Salvage prostate intensity modulated radiation therapy after cryotherapy failure.

Cryotherapy is an ablative therapy that can be used to treat localized prostate cancer. In case of recurrence, treatment options are not well-defined, and their outcomes are unknown. We therefore collected all patients treated with radiotherapy after cryotherapy for prostate cancer recurrence in Nantes (France) between 2012 and 2019. We identified ten patients. After a median follow-up of 5 years, two patients presented late grade 3 toxicities; one patient presented a grade 3 rectal hemorrhage, and one had a grade 3 hematuria. Two patients relapsed at 61 and 62 months, and three patients died of other causes. Radiotherapy to treat local prostate cancer recurrence after cryotherapy seems feasible and effective in local control. These results do not allow us to recommend this technique in current practice but are encouraging for the conduct of prospective trials.

A machine learning approach for predicting radiation-induced hypothyroidism in patients with nasopharyngeal carcinoma undergoing tomotherapy.

The purpose of this study was to establish an integrated predictive model that combines clinical features, DVH, radiomics, and dosiomics features to predict RIHT in patients receiving tomotherapy for nasopharyngeal carcinoma. Data from 219 patients with nasopharyngeal carcinoma were randomly divided into a training cohort (n = 175) and a test cohort (n = 44) in an 8:2 ratio. RIHT is defined as serum thyroid-stimulating hormone (TSH) greater than 5.6 µU/mL, with or without a decrease in free thyroxine (FT4). Clinical features, 27 DVH features, 107 radiomics features and 107 dosiomics features were extracted for each case and included in the model construction. The least absolute shrinkage and selection operator (LASSO) regression method was used to select the most relevant features. The eXtreme Gradient Boosting (XGBoost) was then employed to train separate models using the selected features from clinical, DVH, radiomics and dosiomics data. Finally, a combined model incorporating all features was developed. The models were evaluated using receiver operating characteristic (ROC) curves and decision curve analysis. In the test cohort, the area under the receiver operating characteristic curve (AUC) for the clinical, DVH, radiomics, dosiomics and combined models were 0.798 (95% confidence interval [CI], 0.656-0.941), 0.673 (0.512-0.834), 0.714 (0.555-0.873), 0.698 (0.530-0.848) and 0.842 (0.724-0.960), respectively. The combined model exhibited higher AUC values compared to other models. The decision curve analysis demonstrated that the combined model had superior clinical utility within the threshold probability range of 1% to 79% when compared to the other models. This study has successfully developed a predictive model that combines multiple features. The performance of the combined model is superior to that of single-feature models, allowing for early prediction of RIHT in patients with nasopharyngeal carcinoma after tomotherapy.

Quality of life in patients with nasopharyngeal carcinoma receiving IMRT vs IMPT: a multicenter prospective longitudinal study.

PURPOSE: Nasopharyngeal carcinoma (NPC) patients may experience symptom distress and depression during and after radiation therapy, which negatively impacts quality of life (QOL). We sought to identify trajectories of symptom distress, depression, social support, and QOL in patients with NPC receiving intensity-modulated radiation therapy (IMRT) vs intensity-modulated proton therapy (IMPT). METHODS: A multicenter prospective longitudinal study recruited NPC patients from two leading medical centers in Taiwan. The 121 NPC patients were followed from before RT (T0), at 4 weeks after beginning RT (T1), at 6 weeks of RT or the end of treatment (T2), and at 4 weeks post-RT (T3). Generalized estimating equation analysis was used to identify the factors related to QOL. RESULTS: Patients' symptom distress and depression increased from T0, peaked at T2, and decreased at T3. Physical-QOL and psychosocial-QOL decreased from T0 to T2, then increased by T3. Patients who had early-stage cancer, received a lower RT dose, had less symptom distress, and had less depression were more likely to have better QOL. Greater physical-QOL was associated with IMPT receipt, higher education level, early cancer stage, lower radiation dose, less symptom distress, and less depression. Patients who had good physical performance, received a lower radiation dose, had less symptom distress, and had less depression were more likely to have better psychosocial-QOL. CONCLUSION: Radiation dose, symptom distress, and depression were the most important factors affecting QOL in patients with NPC. Understanding the factors associated with the trajectory of QOL can guide care during radiation treatment.

Deletion of concurrent chemotherapy on the basis of sequential chemoradiotherapy for non-metastatic stage T4 nasopharyngeal carcinoma in IMRT era.

PURPOSE: Intensity-modulated radiotherapy (IMRT) combined with concurrent chemotherapy is deemed as the mainstay treatment in locoregionally advanced nasopharyngeal carcinoma (NPC). Nevertheless, the tolerance of severe acute toxicity of concurrent chemotherapy was unsatisfied. In addition, T4 is the predicting factor of poor prognosis for NPC patients. In this retrospective analysis, the long-term outcomes IMRT combined by induction chemotherapy deleting concurrent chemotherapy with or without adjuvant chemotherapy for T4 non-metastatic NPC were analyzed. MATERIALS AND METHODS: From January 2005 to November 2016, a total of 145 biopsy-proven non-metastatic T4 NPC was treated with IMRT combined by induction chemotherapy with or without adjuvant chemotherapy. The survival and side effects of the patients were analyzed. RESULTS: Median follow-up time was 74 months (ranges, 8-186 months). 10.0%, 61.3%, 27.3%, and 1.3% developed grade 1, 2, 3, and 4 mucositis during IMRT, respectively. 5.5% and 2.0% patients experienced grade 1 and 2 nausea and vomiting; no patients developed grade 3 or 4 nausea and vomiting. Of 145 patients enrolled, 5-year and 10-year overall survival(OS) rates were 73.7% and 53.9%, local progression-free survival(LPFS) rates were 86.1% and 71.6%, regional progression-free survival(RPFS) rates were 96.7% and 92.8%, distant metastasis-free survival (DMFS) rates were 86.7%, 78.2%, respectively. At the last follow-up, five patients developed cranial nerve injury, one patient developed mandibular bone necrosis, four patients developed temporal lobe injury, four patients developed nasopharyngeal massive hemorrhage (three cases after recurrence and one case without recurrence), and five patients developed second primary tumor. CONCLUSION: The survival outcomes of treating T4 NPC IMRT combined by induction chemotherapy deleting concurrent chemotherapy with or without adjuvant chemotherapy are encouraging. Moreover, mucosal reaction, nausea, and vomiting reaction were reduced during IMRT.

Probability of normal tissue complications for hematologic and gastrointestinal toxicity in postoperative whole pelvic radiotherapy for gynecologic malignancies using intensity-modulated proton therapy with robust optimization.

This retrospective treatment-planning study was conducted to determine whether intensity-modulated proton therapy with robust optimization (ro-IMPT) reduces the risk of acute hematologic toxicity (H-T) and acute and late gastrointestinal toxicity (GI-T) in postoperative whole pelvic radiotherapy for gynecologic malignancies when compared with three-dimensional conformal radiation therapy (3D-CRT), intensity-modulated X-ray (IMXT) and single-field optimization proton beam (SFO-PBT) therapies. All plans were created for 13 gynecologic-malignancy patients. The prescribed dose was 45 GyE in 25 fractions for 95% planning target volume in 3D-CRT, IMXT and SFO-PBT plans and for 99% clinical target volume (CTV) in ro-IMPT plans. The normal tissue complication probability (NTCP) of each toxicity was used as an in silico surrogate marker. Median estimated NTCP values for acute H-T and acute and late GI-T were 0.20, 0.94 and 0.58 × 10-1 in 3D-CRT; 0.19, 0.65 and 0.24 × 10-1 in IMXT; 0.04, 0.74 and 0.19 × 10-1 in SFO-PBT; and 0.06, 0.66 and 0.15 × 10-1 in ro-IMPT, respectively. Compared with 3D-CRT and IMXT plans, the ro-IMPT plan demonstrated significant reduction in acute H-T and late GI-T. The risk of acute GI-T in ro-IMPT plan is equivalent with IMXT plan. The ro-IMPT plan demonstrated potential clinical benefits for reducing the risk of acute H-T and late GI-T in the treatment of gynecologic malignances by reducing the dose to the bone marrow and bowel bag while maintaining adequate dose coverage to the CTV. Our results indicated that ro-IMPT may reduce acute H-T and late GI-T risk with potentially improving outcomes for postoperative gynecologic-malignancy patients with concurrent chemotherapy.

[Prevention, diagnosis and management of osteoradionecrosis: Where do we stand?] / Prévention, diagnostic et prise en charge de l'ostéoradionécrose : où en est-on ?

Osteoradionecrosis (ORN) is a late secondary iatrogenic complication of external radiotherapy for cancers of the upper aero-digestive tract. Despite the systematization of intensity-modulated radiotherapy and its potential for preserving salivary secretion and limiting the dose delivered to the supporting bone, ORN remains a feared and frequent complication. The objective of this literature review was to provide an overview of the management of ORN and to determine the key points that would make it possible to improve patient care. The diagnosis of ORN requires to eliminate tumor recurrence then is based on clinical arguments and imaging by CT or Cone Beam evolving in a chronic mode (more than 3-6 months). The harmonization of its classifications aims to offer comprehensive and multidisciplinary care as early as possible. Primary prevention is based on pre-therapeutic oral and dental preparation, then associated with fluoroprophylaxis if salivary recovery is insufficient and requires supervision of invasive dental care and prosthetic rehabilitation. Semi-automatic contouring tools make it possible to identify doses delivered to dental sectors and guide dental care with personalized dosimetric mapping. Conservative medical treatment is offered at an early stage where innovative medical treatments, highlighted by early studies, could be of interest in the future. In the event of advanced ORN, a non-conservative treatment is then proposed and frequently consists of interruptive mandibulectomy associated with reconstruction by bony free flap, the conditions of implantation remaining to be defined with the support of prospective clinical trials.