RESUMEN

Multi-modal therapies for gynecological cancers management may determine a wide range of side effects which depend on therapy-related factors and patient characteristics and comorbidities. Curative or adjuvant pelvic radiotherapy is linked with acute and late toxicity due to irradiation of organs at risk, as small and large bowel, rectum, bladder, pelvic bone, vagina and bone marrow. Successful toxicity management varies with its severity, Radiation Centre practice and experience and skills of radiation oncologists. This position paper was designed by the Italian Association of Radiation and Clinical Oncology Gynecology Study Group to provide radiation oncologists with evidence-based strategies to prevent and manage acute and late toxicities and follow-up recommendations for gynecological cancer patients submitted radiotherapy. Six workgroups of radiation oncologists with over 5 years of experience in gynecologic cancers were setup to investigate radiotherapy-related toxicities. For each topic, PubMed database was searched for relevant English language papers from January 2005 to December 2022. Titles and abstracts of results were checked to verify suitability for the document. Reference lists of selected studies and review papers were added if pertinent. Data on incidence, etiopathogenesis, prevention, treatment and follow-up of acute and late side effects for each organ at risk are presented and discussed.

Asunto(s)

RESUMEN

Background and Objectives: This study aimed to investigate the clinical course and characteristics of late toxicity over time following the completion of definitive radiotherapy (RT) in patients with cervical cancer. Materials and Methods: We retrospectively reviewed the medical records of 60 patients with cervical cancer who underwent pelvic external beam radiotherapy followed by intracavitary brachytherapy. Late toxicity was assessed for the lower gastrointestinal (GI) tract and bladder organ at 6, 12, 24, 36, and >36 months post-RT. We examined the onset and prevalence of late toxicity at each time point. Clinical remission and interventions for managing late toxicity were also investigated. Results: The peak onset of lower GI toxicity occurred 12 months after RT completion, with a median symptom duration of 9.9 months (range, 0.1-26.3 months), and exhibited its highest prevalence rate of 15.5% at 24 months post-RT. Most GI toxicities developed and resolved within three years post-RT, with a prevalence rate of 8.1% at three years, followed by a decreasing trend. Bladder toxicity first peaked at 24 months post-RT and continued to occur beyond 36 months, showing the re-increasing pattern in the prevalence rate after 36 months (23.5%). In terms of clinical remission, 66.7% of lower GI toxicities (12 of 18 patients) and 60% of bladder toxicities (9 of 15 patients) achieved complete remission by the last follow-up date. Conclusions: Late toxicities of the GI and bladder following definitive RT in cervical cancer are partially reversible and exhibit distinct patterns of onset and prevalence over time. A systematic follow-up strategy should be established for the early detection and timely intervention of late toxicity by understanding these clinical courses.

Asunto(s)

RESUMEN

INTRODUCTION: The aim of this study was to evaluate the systemic sequelae, as well as the dental and craniofacial development, of patients with rhabdomyosarcoma in relation to the treatment received and clinical-pathological variables. MATERIALS AND METHODS: A retrospective cross-sectional study was performed. All individuals diagnosed with RMS between 1990 and 2022 were considered eligible. Cases who survived the primary tumor were included. Data were collected from medical records, and patients were called for clinical and radiographic examinations. RESULTS: Thirty-eight patients were assessed, with a mean disease-free survival of 216.68 months (±84.99). The primary location of the tumor was mainly the head and neck region (57.9 %). All patients received chemotherapy, and 30 (78.9 %) also underwent radiotherapy. The most frequently observed sequela was sensory impairment, which was significantly associated with tumors in the head and neck (p < 0.05), as well as with the use of radiotherapy (p = 0.034). Root formation failure was observed in 60 % of cases, microdontia in 50 %, and delayed tooth eruption in 40 %. A convex profile was predominant (80 %), along with maxillary (50 %) and mandibular (80 %) retrusion and a skeletal class II diagnosis (60 %). CONCLUSIONS: Late systemic, dental, and craniofacial developmental sequelae are observed in pediatric rhabdomyosarcoma survivors, especially in patients who underwent radiotherapy in the head and neck region. Younger individuals at the time of treatment are at greater risk of late sequelae.

RESUMEN

Purpose: Rectal toxicity after prostate cancer (PCa) radiation therapy (RT) may be greater with protons compared with photon intensity-modulated RT, perhaps due to lateral penumbra and end-of-range uncertainty. Rectal spacers (RSs) have been shown to mitigate RT-associated acute/late rectal toxicity in men treated with photons. The relative benefit of RS in men treated with protons versus photons is unknown. We hypothesize that RS will confer greater bowel toxicity benefits in PCa treated with protons versus photons. Materials and Methods: We conducted a single institution, retrospective review of men receiving photon intensity-modulated RT or pencil-beam scanning proton RT for localized PCa. Four cohorts were compared: photon with or without RS, and proton with or without RS. Acute (<3 months), late (≥3 months), and most recent toxicity were compared among the 4 cohorts. The cumulative incidence of physician-reported grade 1 to 2 gastrointestinal (GI) toxicity (common terminology criteria for adverse events V5.0) was compared using χ2 or Fisher exact test. Patient-reported toxicity was evaluated using the International Prostate Expanded Prostate Composite Index-Clinical Practice and compared using linear mixed modeling. Results: In total, 164 patients were eligible for analysis: 38 photons without RS, 50 photons with RS, 26 protons without RS, and 50 protons with RS. The median follow-up was 17.6 months. In proton patients, acute (6.12% vs 30.77%, P = .009) and most recent (4.26% vs 26.09%, P = .01) G1-2 GI toxicity was lower with versus without RS. In photon patients, there were no significant differences in toxicity with versus without RS. No significant differences in patient-reported outcomes were observed with versus without RS in photon or proton groups. Conclusion: The rectal spacer was associated with lower G1-2 acute and most recent GI toxicity in men treated with protons; this difference was not observed in men treated with photons. While this study is limited by sample size, a relatively greater benefit of RS with proton versus photon therapy was observed.

RESUMEN

Objective: A favorable effect of ultra-high dose rate (FLASH) radiation on normal tissue-sparing has been indicated in several preclinical studies. In these studies, the adverse effects of radiation damage were reduced without compromising tumor control. Most studies of proton FLASH investigate these effects within the entrance of a proton beam. However, the real advantage of proton therapy lies in the Spread-out Bragg Peak (SOBP), which allows for giving a high dose to a target with a limited dose to healthy tissue at the entrance of the beam. Therefore, a clinically relevant investigation of the FLASH effect would be of healthy tissues within a SOBP. Our study quantified the tissue-sparing effect of FLASH radiation on acute and late toxicity within an SOBP in a murine model. Material/Methods: Radiation-induced damage was assessed for acute and late toxicity in the same mice following irradiation with FLASH (Field dose rate of 60 Gy/s) or conventional (CONV, 0.34 Gy/s) dose rates. The right hindleg of unanesthetized female CDF1 mice was irradiated with single-fraction doses between 19.9-49.7 Gy for CONV and 30.4-65.9 Gy for FLASH with 5-8 mice per dose. The leg was placed in the middle of a 5 cm SOBP generated from a mono-energetic beam using a 2D range modulator. Acute skin toxicity quantified by hair loss, moist desquamation and toe separation was monitored daily within 29 days post-treatment. Late toxicity of fibrotic development measured by leg extendibility was monitored biweekly until 30 weeks post-treatment. Results: Comparison of acute skin toxicity following radiation indicated a tissue-sparing effect of FLASH compared to conventional single-fraction radiation with a mean protection ratio of 1.40 (1.35-1.46). Fibrotic development similarly indicated normal tissue sparing with a 1.18 (1.17-1.18) protection ratio. The acute skin toxicity tissue sparing was similar to data from entrance-beam irradiations of Sørensen et al. (4). Conclusion: Full dose-response curves for acute and late toxicity after CONV and FLASH radiation were obtained. Radiation within the SOBP retains the normal-tissue-sparing effect of FLASH with a dose-modifying factor of 40% for acute skin damage and 18% for fibrotic development.

RESUMEN

BACKGROUND AIMS: There are few descriptions of the epidemiology of chronic liver disease (CLD) after allogeneic hematopoietic stem cell transplantation (allo-HCT). Among those transplanted before 2000, viral hepatitis was the dominant cause of CLD. Recently, the prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD, previously known as nonalcoholic fatty liver disease) is increasing in the general population. In addition, survivors of allo-HCT are known to be at increased risk of metabolic syndrome. We set out to describe the epidemiology of CLD in a modern cohort of allo-HCT recipients. We hypothesized that MASLD would be the most common cause of CLD in the cohort. METHODS: We undertook a retrospective cohort and nested case-control study of 2-year survivors of allo-HCT in Alberta transplanted between 2008 and 2018. RESULTS: Among 392 2-year survivors of allo-HCT between 2008 and 2018, the prevalence of CLD was 41.8% and MASLD was identified in 56% of those with CLD, followed by iron overload in 47% of those with CLD. The prevalence of MASLD among the entire cohort was 46%. Although most patients developed CLD before 2 years post-transplant, there was a 13% cumulative incidence of new CLD after 2 years posttransplant. Grade 2-4 acute graft-versus-host disease and/or moderate-to-severe chronic graft-versus-host disease and pretransplant CLD were strongly associated with CLD. In the case-control study examining the association between cardiovascular risk factors and CLD, type 2 diabetes was associated with CLD. Cirrhosis developed in 1.5% of survivors, and MASLD was an underlying etiology in one half of these cases. There was no difference in overall survival and non-relapse mortality between those who did and did not develop CLD. CONCLUSIONS: MASLD is the main cause of CLD in recent long-term survivors of allo-HCT and may be associated with post-transplant corticosteroid exposure and type 2 diabetes. We note a shift in the underlying etiology of CLD post-HCT: previous studies describe viral hepatitis as the most common cause of CLD. The high prevalence of MASLD in allo-HCT recipients has important implications for survivorship care.

RESUMEN

The usefulness of moderately hypofractionated radiotherapy for localized prostate cancer has been extensively reported, but there are limited studies on proton beam therapy (PBT) using similar hypofractionation schedules. The aim of this prospective phase II study is to confirm the safety of a shortened PBT course using 70 Gy relative biological effectiveness (RBE) in 28 fractions. From May 2013 to June 2015, 102 men with localized prostate cancer were enrolled. Androgen deprivation therapy was administered according to risk classification. Toxicity was assessed using Common Terminology Criteria for Adverse Events version 4.0. Of the 100 patients ultimately evaluated, 15 were classified as low risk, 43 as intermediate risk, and 42 as high risk. The median follow-up time of the surviving patients was 96 months (range: 60-119 months). The 5-year cumulative incidences of grade 2 gastrointestinal/genitourinary adverse events were 1% (95% CI: 0.1-6.9) and 4% (95% CI: 1.5-10.3), respectively; no grade ≥ 3 gastrointestinal/genitourinary adverse events were observed. The current study revealed a low incidence of late adverse events in prostate cancer patients treated with moderately hypofractionated PBT of 70 Gy (RBE) in 28 fractions, indicating the safety of this schedule.

Asunto(s)

RESUMEN

PURPOSE: Radiotherapy (RT) with concomitant cisplatin (CRT) or cetuximab (ERT) are accepted treatment options for locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN). Long-term adverse events (AEs) have a vast impact on patients' quality of life. This study explored tissue biomarkers which could help predict late toxicity. METHODS/PATIENTS: Single-institution prospective study including patients aged ≥ 18 with histologically confirmed newly diagnosed LA-SCCHN treated with RT and either concomitant cisplatin q3w or weekly cetuximab, according to institutional protocols. All patients underwent pre- and post-treatment skin biopsies of neck regions included in the clinical target volume. Angiogenesis, macrophages, and extracellular matrix (ECM) markers were evaluated by immunohistochemistry (IHC). RESULTS: From April 15, 2016, to December 11, 2017; 31 patients were evaluated [CRT = 12 (38.7%) and ERT = 19 (61.3%)]. 27 patients (87%) had received induction chemotherapy. All patients finished RT as planned. IHC expression of vasculature (CD34) and collagen (Masson's Trichrome) did not differ significantly between and within CRT and ERT arms. Conversely, an increased CD68 and CD163 macrophage infiltration expression was observed after treatment, without significant impact of treatment modality. Patients with higher late toxicity showed lower expression of macrophage markers in pre-treatment samples compared with those with lower late toxicity, with statistically significant differences for CD68. CONCLUSIONS: Angiogenesis and ECM biomarkers did not differ significantly between CRT and ERT. Macrophage markers increased after both treatments and deserve further investigation as predictors of late toxicity in LA-SCCHN patients. [Protocol code: TOX-TTCC-2015-01/Spanish registry of clinical studies (REec): 2015-003012-21/Date of registration: 27/01/2016].

RESUMEN

Purpose: This study aimed to evaluate 5-year outcomes and the late toxicity profile of chrono-chemotherapy with different infusion rates in patients with locally advanced nasopharyngeal carcinoma (NPC). Methods and materials: Our retrospective analysis included 70 patients with locally advanced NPC stages III and IVB (according to the 2010 American Joint Committee on Cancer staging system). Patients were treated with two cycles of induction chemotherapy (IC) before concurrent chemoradiotherapy (CCRT) at Guizhou Cancer Hospital. The IC with docetaxel, cisplatin (DDP) and fluorouracil regimen. Patients were divided into two groups during CCRT. Using a "MELODIE" multi-channel programmed pump, DDP (100 mg/m2) was administered for 12 hours from 10:00 am to 10:00 pm and repeated every 3 weeks for 2-3 cycles. DDP was administered at the peak period of 4:00 pm in the sinusoidal chrono-modulated infusion group (Arm A, n=35). The patients in Arm B received a constant rate of infusion. Both arms received radiotherapy through the same technique and dose fraction. The long-term survival and disease progression were observed. Results: After a median follow-up of 82.8 months, the 5-year progression-free survival rate was 81.3% in Arm A and 79.6% in Arm B (P = 0.85). The 5-year overall survival rate was not significantly different between Arm A and Arm B (79.6% vs 85.3%, P = 0.79). The 5-year distant metastasis-free survival rate was 83.6% in Arm A and 84.6% in Arm B (P = 0.75). The 5-year local recurrence-free survival rate was 88.2% in Arm A and 85.3% in Arm B (P = 0.16). There were no late toxicities of grade 3-4 in either group. Both groups had grade 1-2 late toxicities. Dry mouth was the most common late toxic side effect, followed by hearing loss and difficulty in swallowing. There was no statistically significant difference between Arm A and Arm B in terms of side effects. Conclusion: Long-term analysis confirmed that in CCRT, cisplatin administration with sinusoidal chrono-modulated infusion was not superior to the constant infusion rate in terms of long-term toxicity and prognosis.

RESUMEN

Radiation toxicities may be underestimated after treatment of transitional cell carcinoma in dogs' lower urinary tract. Assessing acute and late toxicities and differentiating them from progressive disease (PD) impacts further therapeutic approach. We retrospectively assessed dogs treated with definitive-intent chemoradiotherapy (12 × 3.8 Gy, various first-line chemotherapeutics). Local tumour control, radiation toxicities and survival were evaluated. We classified radiation toxicities according to the previously published radiation toxicity scheme "VRTOG" as well as the updated version, "VRTOG_v2.0". Fourteen dogs with transitional cell carcinoma of bladder ± urethra (n = 8), +prostate (n = 3) or solely urethra (n = 3), were included. Median follow-up was 298 days (range 185-1798 days), median overall survival 305 days (95%CI = 209;402) and 28.6% deaths were tumour-progression-related. Acute radiation toxicity was mild and self-limiting with both classification systems: In VRTOG, 5 dogs showed grade 1, and 1 dog grade 2 toxicity. In VRTOG_v2.0, 2 dogs showed grade 1, 3 dogs grade 2, and 3 dogs grade 3 toxicity. Late toxicity was noted in 14.2% of dogs (2/14) with the VRTOG, both with grade 3 toxicity. With VRTOG_v2.0, a larger proportion of 42.9% of dogs (6/14) showed late toxicities: Four dogs grade 3 (persistent incontinence), 2 dogs grade 5 (urethral obstructions without PD resulting in euthanasia). At time of death, 5 dogs underwent further workup and only 3 were confirmed to have PD. With the updated VRTOG_v2.0 classification system, more dogs with probable late toxicity are registered, but it is ultimately difficult to distinguish these from disease progression as restaging remains to be the most robust determinant.

Asunto(s)

RESUMEN

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) after curative treatment for testicular germ cell tumors (GCTs) has been previously reported. It has been shown that CIPN can contribute to impaired quality of life (QOL) in cancer survivors. Herein, we aimed to evaluate CIPN in association with QOL in GCT survivors. PATIENTS AND METHODS: European Organization for Research and Treatment of Cancer (EORTC) Quality of Life - Chemotherapy-Induced Peripheral Neuropathy questionnaire (QLQ-CIPN20) and Quality of Life Questionnaire (QLQ-C30) were prospectively completed by GCT survivors (N = 151) at National Cancer Institute in Slovakia during their annual follow-up. The median follow-up was 10 years (range 4-30). Upon obtaining the scores from each questionnaire, each score from QLQ-C30 was correlated with CIPN defined as high or low (above and below median) as obtained from CIPN20. RESULTS: GCT survivors with high overall CIPN score reported impaired QOL in QLQ-C30. The global health status was lower in survivors with high CIPN versus low CIPN (mean score ± SEM: 67.17 ± 2.00 vs. 86.18 ± 1.76, P < .00001). Survivors with high CIPN reported worse physical, role, emotional, cognitive, and social functioning compared to survivors with low CIPN (all P < .00001). CIPN high survivors perceived more fatigue, nausea, pain, dyspnea, sleeping disorders, and appetite loss compared to CIPN low survivors (all P < .004). Higher burden of CIPN was associated with more financial problems vs CIPN low (mean score ± SEM: 19.70 ± 2.64 vs. 6.67 ± 2.32, P = .00025). Spearman analysis has confirmed negative correlation of overall CIPN20 score with QLQ-C30 global health status (R = -0.53, P < .0001). CONCLUSION: CIPN is a strong predictor of impairment in QOL among GCT survivors. Molecular mechanisms of neurotoxicity should be intensively studied to find preventive and therapeutic strategies.

Asunto(s)

RESUMEN

BACKGROUND: Radiation therapy is often indicated as part of the treatment for breast cancer and is therefore used frequently worldwide. Vasculopathy is a general term used to describe any condition that affects blood vessels. We present a case report of a patient who presented with vasculopathy as a rare late side effect of radiation therapy to the breast. CASE PRESENTATION: This 66-year-old woman was initially treated with breast-conserving surgery for early-stage receptor-positive left breast carcinoma. She received postoperative radiation therapy and hormonal treatment with tamoxifen. She developed sudden spontaneous painless ecchymosis spread over the whole irradiated area 1.5 years after finishing her radiation therapy. Tumor relapse was excluded. There was no associated vasculitis. The cause was presumed to be multifactorial. She had a history of smoking and was known to have hyperlipidemia. She had undergone several surgical treatments at the left breast one year after her initial breast-conserving treatment and was taking tamoxifen. Anti-inflammatory medicine and treatments increasing local blood flow were prescribed. The ecchymosis resolved completely within one month. CONCLUSIONS: Vasculopathy can occur as a rare late side effect of radiation therapy. It can be reversible. Prevention begins with carefully treating precipitating factors.

Asunto(s)

RESUMEN

BACKGROUND AND PURPOSE: To quantify patient-reported 2-year intestinal toxicity (IT) from pelvic nodal irradiation (PNI) for prostate cancer. The association between baseline/acute symptoms and 2-year worsening was investigated. MATERIALS AND METHODS: Patient-reported IT was prospectively assessed through the Inflammatory Bowel Disease Questionnaire (IBDQ), filled in at baseline, radiotherapy mid-point and end, at 3 and 6 months and every 6 months until 5 years. Two-year deterioration of IBDQ scores relative to the Bowel Domain was investigated for 400 patients with no severe baseline symptoms and with questionnaires available at baseline, 2 years, RT mid-point and/or end and at least three follow-ups between 3 and 18 months. The significance of the 2-year differences from baseline was tested. The association between baseline values and ΔAcute (the worst decline between baseline and RT mid-point/end) was investigated. RESULTS: In the IBDQ lower scores indicate worse symptoms. A significant (p < 0.0001) 2-year mean worsening, mostly in the range of -0.2/-0.4 points on a 1-7 scale, emerged excepting one question (IBDQ29, "nausea/feeling sick"). This decline was independent of treatment intent while baseline values were associated with 2-year absolute scores. The ΔAcute largely modulated 2-year worsening: patients with ΔAcute greater than the first quartile (Q1) and ΔAcute less or equal than Q1 showed no/minimal and highly significant (p < 0.0001) deterioration, respectively. Rectal incontinence, urgency, frequency and abdominal pain showed the largest mean changes (-0.5/-1): risk of severe worsening (deemed to be of clinical significance if ≤ 2) was 3-5 fold higher in the ΔAcute ≤ Q1 vs ΔAcute > Q1 group (p < 0.0001). CONCLUSION: A modest but significant deterioration of two-year patient-reported intestinal symptoms from PNI compared to baseline was found. Patients experiencing more severe acute symptoms are at higher risk of symptom persistence at 2 years, with a much larger prevalence of clinically significant symptoms.

Asunto(s)

RESUMEN

BACKGROUND/PURPOSE: The long-term clinical impact of prostate position-based image-guided radiotherapy (IGRT) for localized prostate cancer remains unclear. MATERIALS AND METHODS: We retrospectively compared clinical outcomes following intensity-modulated radiation therapy (IMRT) with cone-beam computed tomography-based prostate position-based IGRT (P-IGRT) or without P-IGRT (non-P-IGRT). From June 2011, we applied P-IGRT in IMRT for intermediate-risk (IR) prostate cancer (PCa) (D'Amico risk classification) (76 Gy in 38 fractions, with smaller margins). Clinical outcomes of patients who received P-IGRT between June 2011 and June 2019 were retrospectively compared with those of patients with IR PCa who received IMRT without P-IGRT between October 2002 and May 2011 in our institution (74 Gy in 37 fractions). RESULTS: A total of 222 consecutive patients were analyzed: 114 in the P-IGRT cohort and 108 in the non-P-IGRT cohort. The median follow-up period after IMRT was 7.1 years for the P-IGRT cohort and 10.8 years for the non-P-IGRT cohort. The biochemical failure-free rate was significantly better in the P-IGRT cohort (94.9% for the P-IGRT cohort vs 82.7% for the non-P-IGRT cohort at 10 years, p = 0.041). The rate of rectal bleeding which needs intervention including the use of suppositories was significantly lower in the P-IGRT cohort (p < 0.001). CONCLUSIONS: The use of P-IGRT with higher doses and smaller margins was correlated with significantly better biochemical control, and a lower incidence of rectal bleeding in IMRT for intermediate-risk prostate cancer. The enhanced accuracy using P-IGRT has the potential to independently improve disease control and reduce late rectal bleeding.

Asunto(s)

RESUMEN

BACKGROUND: Breast cancer is the most common cancer in women. Radiotherapy is an important part of breast cancer treatment after surgery. Breast cancer radiotherapy is usually delivered in 3-5 weeks. This is a long duration for women with breast cancer to stay away from the family and work. We wanted to reduce this duration so that the wages loss and the logistics can be minimised for these patients. Hypofractionation, i.e. high dose per fraction, is delivered in a smaller number of days. In this study, we will compare a 1-week schedule of hypofractionated adjuvant whole breast/chest wall and/or regional nodal radiotherapy against 2 weeks for locoregional disease control, toxicities, quality of life (QoL), survival and second cancers after primary surgery in patients with breast cancer. METHODS: Eligible patients with breast cancer after mastectomy or breast conserving surgery (BCS) will be treated with a radiotherapy dose of 26 Gy in 5 fractions over 1 week in the study arm and 34 Gy in 10 fractions over 2 weeks in the control arm. The primary endpoint of this noninferiority study will be locoregional tumour control. Secondary endpoints will be early and late radiation toxicities, quality of life, contralateral primary tumours, regional and distant metastases, survival and second cancers. A total of 1018 patients will be randomised (1:1) to receive 1 week or 2 weeks of radiotherapy. An event-driven analysis will be performed after at least 94 patients have documented locoregional recurrences. Acute radiation toxicity will be assessed and scaled according to the RTOG grading system. Late radiation toxicity will be assessed with the Radiation Therapy Oncology Group and the European Organisation for Research and Treatment of Cancer late radiation morbidity scale. Cosmetic assessment will be done using Harvard/NSABP/RTOG breast cosmesis grading scale at baseline and 3 and 5 years. QoL will be assessed with EORTC QLQ-30 and EORTC QLQ-BR 23 at baseline and 3 and 5 years. DISCUSSION: Hypofractionation reduces treatment time to half while maintaining breast cosmesis and gives control rates equal to conventional fractionation. This is possible because breast tissue can tolerate high dose per fraction. In this study, we presume that 1-week radiotherapy will be non-inferior to 2 week radiotherapy, i.e. disease control will be similar with both the schedules without additional side effects, and QoL of these patients will be maintained. If we are able to achieve these outcomes, then patients will be able to complete their radiotherapy in less duration. There is not much data on regional nodal irradiation with hypofraction in breast cancer. We have used hypofraction for regional nodal irradiation in the past and not encountered any safety issue. If we are able to prove that late-term effects are comparable in the two schedules, it will make the radiation oncologist confident about hypofractionation in breast cancer. As breast cancer is a leading cancer in females and radiation therapy is an integral part of its local management, hypofractionation will help radiation centres worldwide to meet the growing need for radiation treatment in breast cancer, particularly in developing countries where resources are limited. It will also reduce the financial burden on the patient and family. Since we will treat these patients with both simple and complex radiotherapy techniques, it will also be possible for the low-income countries to follow this trial without needing a high-end or expensive radiotherapy equipment as the planning and treatment process will be very simple. TRIAL REGISTRATION: The trial is registered with ClinicalTrials.gov ID NCT04472845 and CTRI with REF/2020/09/037050.

Asunto(s)

RESUMEN

Despite advances in head and neck cancer treatment, virtually all patients experience chemoradiation-induced toxicities. Oral mucositis (OM) and dysphagia are among the most prevalent and have a systemic impact on patients, hampering treatment outcome and harming quality of life. Accurate prediction of severe cases is crucial for improving management strategies and, ultimately, patient outcomes. This scoping review comprehensively maps the reported predictors and critically evaluates the performance, methodology, and reporting of predictive models for these conditions. A total of 174 studies were identified from database searches, with 73 reporting OM predictors, 97 reporting dysphagia predictors, and 4 reporting both OM and dysphagia predictors. These predictors included patient demographics, tumor classification, chemoradiotherapy regimen, radiation dose to organs-at-risk, genetic factors, and results of clinical laboratory tests. Notably, many studies only conducted univariate analysis or focused exclusively on certain predictor types. Among the included studies, numerous predictive models were reported: eight for acute OM, five for acute dysphagia, and nine for late dysphagia. The area under the receiver operating characteristic curve (AUC) ranged between 0.65 and 0.81, 0.60 and 0.82, and 0.70 and 0.85 for acute oral mucositis, acute dysphagia, and late dysphagia predictive models, respectively. Several areas for improvement were identified, including the need for external validation with sufficiently large sample sizes, further standardization of predictor and outcome definitions, and more comprehensive reporting to facilitate reproducibility.

RESUMEN

Radiation can induce DNA double-stranded breaks, which are typically detected by the fluorescence of phosphorylated histone H2AX. In this study, we examined the usefulness of the dynamics of radiation-induced gamma-H2AX foci of peripheral blood lymphocytes (PBLs), as a marker of DNA repair ability, in predicting late adverse events from radiotherapy. A total of 46 patients with cervical, vaginal and anal canal cancers treated with radical radiotherapy between 2014 and 2019 were included in this analysis. Concurrent chemotherapy was administered in 36 cases (78.3%). Peripheral blood was obtained before treatment, and then irradiated ex vivo with 1 Gy X-ray. The ratio of radiation-induced gamma-H2AX foci in PBLs measured at 30 min and at 4 h was defined as the foci decay ratio (FDR). With a median follow-up of 54 months, 9 patients (19.6%) were observed to have late genitourinary or gastrointestinal (GU/GI) toxicity. The FDR ranged from 0.51 to 0.74 (median 0.59), with a significantly higher incidence of Grade 1 or higher late adverse events in the FDR ≥ 0.59 group. In multivariate analysis, FDR ≥ 0.59 and hypertension also emerged as significant factors associated with the development of late toxicities. Overall, our results suggest that measurement of radiation-induced gamma-H2AX foci in PBLs may predict the risk of late GU/GI toxicities from chemoradiotherapy, which can enable tailoring the radiation dose to minimize adverse effects.

Asunto(s)

RESUMEN

Background: FLASH radiotherapy (RT) is a novel method for delivering ionizing radiation, which has been shown in preclinical studies to have a normal tissue sparing effect and to maintain anticancer efficacy as compared to conventional RT. Treatment of head and neck tumors with conventional RT is commonly associated with severe toxicity, hence the normal tissue sparing effect of FLASH RT potentially makes it especially advantageous for treating oral tumors. In this work, the objective was to study the adverse effects of dogs with spontaneous oral tumors treated with FLASH RT. Methods: Privately-owned dogs with macroscopic malignant tumors of the oral cavity were treated with a single fraction of ≥30Gy electron FLASH RT and subsequently followed for 12 months. A modified conventional linear accelerator was used to deliver the FLASH RT. Results: Eleven dogs were enrolled in this prospective study. High grade adverse effects were common, especially if bone was included in the treatment field. Four out of six dogs, who had bone in their treatment field and lived at least 5 months after RT, developed osteoradionecrosis at 3-12 months post treatment. The treatment was overall effective with 8/11 complete clinical responses and 3/11 partial responses. Conclusion: This study shows that single-fraction high dose FLASH RT was generally effective in this mixed group of malignant oral tumors, but the risk of osteoradionecrosis is a serious clinical concern. It is possible that the risk of osteonecrosis can be mitigated through fractionation and improved dose conformity, which needs to be addressed before moving forward with clinical trials in human cancer patients.

RESUMEN

BACKGROUND: We retrospectively analyzed the 5-year biochemical disease-free survival (bDFS) and occurrence of late toxicity in prostate cancer patients treated with pencil beam scanning (PBS) proton radiotherapy. METHODOLOGY: In the period from January 2013 to June 2018, 853 patients with prostate cancer were treated with an ultra-hypofractionated schedule (36.25 GyE/five fractions). The mean PSA value was 6.7 (0.7-19.7) µg/L. There were 318 (37.3%), 314 (36.8%), and 221 (25.9%) patients at low (LR), favorable intermediate (F-IR), and unfavorable intermediate risk (U-IR), respectively. Neoadjuvant hormonal therapy was administered to 197 (23.1%) patients, and 7 (0.8%) patients had adjuvant hormonal therapy. The whole group of patients reached median follow-up time at 62.7 months, and their mean age was 64.8 (40.0-85.7) years. The bDFS rates and late toxicity profile were evaluated. RESULTS: Median treatment time was 10 (7-38) days. Estimated 5-year bDFS rates were 96.5%, 93.7%, and 91.2% for low-, favorable intermediate-, and unfavorable intermediate-risk groups, respectively. Cumulative late toxicity (CTCAE v4.0) of G2+ was as follows: gastrointestinal (GI)-G2: 9.1%; G3: 0.5%; genitourinary (GU)-G2: 4.3%, and no G3 toxicity was observed. PSA relapse was observed in 58 (6.8%) patients: 16 local, 22 lymph node, 4 bone recurrences, and 10 combined sites of relapse were detected. Throughout the follow-up period, 40 patients (4.7%) died, though none due to prostate cancer. CONCLUSION: Ultra-hypofractionated proton beam radiotherapy is an effective treatment for low- and favorable intermediate-risk prostate cancer, with long-term bDFS rates comparable to other techniques. It is promising for unfavorable intermediate-risk prostate cancer and has acceptable long-term GI and favorable GU toxicity.

RESUMEN

Purpose: To report on the late toxicity and local control (LC) of head and neck cancer patients treated with adaptive FDG-PET/CT response-guided radiotherapy (ADMIRE) with dose escalation (NCT03376386). Materials and methods: Between December 2017 and April 2019, 20 patients with stage II-IV squamous cell carcinoma of the larynx, hypopharynx or oropharynx were treated within the ADMIRE study where FDG-PET/CT response-guided (Week 2&4) dose escalation was applied (total dose 70-78 Gy). Cisplatin or cetuximab was added to radiotherapy in case of T3-4 and/or N2c disease. To compare the LC and late toxicity of the study population, we used an external control group (n = 67) consisting of all eligible patients for the study (but not participated). These patients were treated in our institution during the same period with the current standard of 70 Gy radiotherapy. To reduce the effect of confounding, logistic regression analyses was done using stabilized inverse probability of treatment weighting (SIPTW). Results: After median follow-up of 40 and 43 months for the ADMIRE and control groups, the 3-year LC-rates were 74% and 78%, respectively (adjusted HR after SIPTW 0.80, 95 %CI 0.25-2.52, p = 0.70). The incidences of any late G3 toxicity were 35% and 18%, respectively. The adjusted OR for any late G3 toxicity was 5.09 (95 %CI 1.64-15.8, p = 0.005), for any late G ≥ 2 toxicity was 3.67 (95 %CI 1.2-11.7, p = 0.02), for persistent laryngeal edema was 10.95 (95% CI 2.71-44.29, p = 0.001), for persistent mucosal ulcers was 4.67 (95% CI 1.23-17.7, p = 0.023), and for late G3 radionecrosis was 15.69 (95 %CI 2.43-101.39, p = 0.004). Conclusion: Given the comparable LC rates with increased late toxicity in the ADMIRE group, selection criteria for future adaptive dose escalation trials (preferably randomized) need to be refined to include only patients at higher risk of local failure and/or lower risk of severe late toxicity.