Modern Radiotherapy Era Research Articles

Optimizing Hearing Outcomes in Nasopharyngeal Cancer Survivors in the Era of Modern Radiotherapy and Systemic Therapy.

Intensity-modulated radiation therapy (IMRT) improves disease control and reduces treatment-related toxicity in patients with localized nasopharyngeal carcinoma (NPC). However, due to the proximity of the auditory apparatus to the treatment volume and the frequent incorporation of cisplatin-based chemotherapy, treatment-related sensorineural hearing loss (SNHL) remains a common debilitating complication among NPC survivors. The reported crude incidence of SNHL following IMRT for NPC varies widely at 1-46% due to differences in auditory assessment methods and thresholds, follow-up durations, chemotherapy usage, and patient compositions. International guidelines and radiation dosimetric studies have recommended constraining the cochlear mean dose to less than 44-50 Gy, but the risk of SNHL remains high despite adherence to these constraints. Potential strategies to improve hearing outcomes in NPC survivors include cautious de-escalation of radiotherapy dose and volume, individualization of cochlear constraints, optimization of radiotherapy planning techniques, and the use of substitutes or alternative schedules for cisplatin-based chemotherapy. The addition of immune checkpoint inhibitors to chemoradiotherapy did not impact ototoxicity. Prospective studies that employ both objective and patient-reported auditory outcomes are warranted to test the long-term benefits of various approaches. This article aims to provide a comprehensive review of the incidence and radiation dose-toxicity relationship of SNHL in NPC survivors and to summarize potential strategies to optimize hearing outcomes in relation to nuances in radiotherapy planning and the selection of systemic therapy.

Does lower dose pilocarpine have a role in radiation-induced xerostomia in the modern radiotherapy era? A single-center experience based on patient-reported outcome measures

PurposeThis study aims to investigate the efficacy of lower dose pilocarpine in alleviating late dry mouth symptoms in head and neck cancer patients received radiotherapy.MethodsEighteen head and neck cancer patients experiencing persistent dry mouth were enrolled in this study. All participants started pilocarpine treatment a median of 6 months post-radiotherapy. Initially, patients received pilocarpine at 5 mg/day, with a gradual increase to the recommended dose of 15 mg/day. A Patient-Reported Outcome Measurement (PROMs) questionnaire assessed symptoms’ severity related to hyposalivation.ResultsAll patients reported symptomatic dry mouth above grade 2 before starting the medication. Pilocarpine treatment continued based on patients’ self-assessment, with a median duration of 12 months (range, 3–36 months). The median daily maintenance dose was 10 mg (range, 5 to 20 mg). Total PROMs scores significantly decreased following medication, from 13 points (range 7–18 points) to 7 points (range 4–13 points) (p = 0.001). Significant improvements were observed in questions related to dry mouth (p < 0.001), water intake during eating (p = 0.01), carrying water (p = 0.01), taste (p < 0.001), and water intake during speech (p < 0.001). Initial and maintenance doses of pilocarpine were lower, and the duration of pilocarpine usage was shorter in patients treated with intensity-modulated radiation therapy compared to conformal radiotherapy (12 months vs. 25 months, p = 0.04).ConclusionPilocarpine may be considered at doses lower for late-term dry mouth. With modern radiotherapy techniques effectively preserving the parotid gland, short-term use may be recommended in these patients. Future studies may enhance the development of a more robust patient selection criteria model.

Small Bowel Dose Constraints in Radiation Therapy—Where Omics-Driven Biomarkers and Bioinformatics Can Take Us in the Future

Radiation-induced gastrointestinal (GI) dose constraints are still a matter of concern with the ongoing evolution of patient outcomes and treatment-related toxicity in the era of image-guided intensity-modulated radiation therapy (IMRT), stereotactic ablative radiotherapy (SABR), and novel systemic agents. Small bowel (SB) dose constraints in pelvic radiotherapy (RT) are a critical aspect of treatment planning, and prospective data to support them are scarce. Previous and current guidelines are based on retrospective data and experts’ opinions. Patient-related factors, including genetic, biological, and clinical features and systemic management, modulate toxicity. Omic and microbiome alterations between patients receiving RT to the SB may aid in the identification of patients at risk and real-time identification of acute and late toxicity. Actionable biomarkers may represent a pragmatic approach to translating findings into personalized treatment with biologically optimized dose escalation, given the mitigation of the understood risk. Biomarkers grounded in the genome, transcriptome, proteome, and microbiome should undergo analysis in trials that employ, R.T. Bioinformatic templates will be needed to help advance data collection, aggregation, and analysis, and eventually, decision making with respect to dose constraints in the modern RT era.

A multivariable normal tissue complication probability model for predicting radiation-induced hypothyroidism in nasopharyngeal carcinoma patients in the modern radiotherapy era.

Radiation-induced hypothyroidism (RHT) is a common long-term complication for nasopharyngeal carcinoma (NPC) survivors. A model using clinical and dosimetric factors for predicting risk of RHT could suggest a proper dose-volume parameters for the treatment planning in an individual level. We aim to develop a multivariable normal tissue complication probability (NTCP) model for RHT in NPC patients after intensity-modulated radiotherapy or volumetric modulated arc therapy. The model was developed using retrospective clinical data and dose-volume data of the thyroid and pituitary gland based on a standard backward stepwise multivariable logistic regression analysis and was then internally validated using 10-fold cross-validation. The final NTCP model consisted of age, pretreatment thyroid-stimulating hormone and mean thyroid dose. The model performance was good with an area under the receiver operating characteristic curve of 0.749 on an internal (200 patients) and 0.812 on an external (25 patients) validation. The mean thyroid dose at ≤45Gy was suggested for treatment plan, owing to an RHT incidence of 2% versus 61% in the >45Gy group.

The Impact of Cardiac Sparing Techniques on Major Cardiac Events for Patients Undergoing Breast Radiotherapy

In radiotherapy, studies with historical estimates have shown a linear relationship between cardiac dose and risk of major cardiac events with no safe dose threshold. This study investigates the relationship between cardiac dose and event rates for patients undergoing breast radiotherapy with modern heart-sparing techniques, where substantially lower cardiac doses are achieved. From 2008 to 2018, all patients undergoing curative whole breast or chest wall radiotherapy at a tertiary care center were included. In this study, the deep-inspiration breath hold (DIBH) technique was implemented in 2013 as the standard of care for left-sided patients. Cardiacdosimetricdata from the clinical treatment plan was extracted and matched to patients from the ongoing, prospectively collected Alberta Provincial Project for Outcome Assessment in Coronary Heart disease (APPROACH) database that experienced a major adverse cardiac event (MACE). MACE was defined as myocardial infarction, hospitalization for unstable angina, hospitalization for heart failure,or clinically indicated coronary revascularization.For all the left- and right-sided patients, the population event rates, the median time to event, and the average (± standard deviation) of the mean heart physical dose is reported. The proportion of left- and right-sided patients experiencing a major cardiac event were tested for independence using a two-sample z-test for proportions. A student's t-test was used to measure significance for mean heart dose. An alpha of 0.05 was used to indicate significance for both tests. A total of 4893 patients received breast radiotherapy with 2429 left-sided, 2429 right-sided, and 35 synchronous bilateral. For all patients, Table 1 describes laterality, treatment characteristics, and prescription. The median (range) age at the time of first radiotherapy treatment was 59 (23-94). Of these patients with contours available, 96 left-sided (3.9%) and 69 right-sided (2.8%) patients experienced a MACE (p = 0.03) with a mean heart dose of 1.4 (±0.7)Gyand 0.5 (±0.2)Gy, in the event cohorts respectively (p < 0.001). The mean time to event was 4.7 (±3.2) years and 4.8 (±3.0) years for left- and right-sided patients, respectively (p = 0.83). For the left-sided cohort treated with DIBH, the mean heart dose is 1.0 (±0.8)Gy. In the era of modern radiotherapy and cardiac-sparing techniques, mean heart dose and corresponding event rates are stillsignificantlyhigher for left-sided patients than right-sided patients. Future work will aim to test whether there is a safe threshold for cardiac dose in the context of these results.

Natural History and Clinical/Dosimetric Determinants of Osteoradionecrosis in a Large Cohort of Head and Neck Cancer Following Curative Radiotherapy: Debunking the Myth of Decreased Rates of Osteoradionecrosis in the Modern Radiotherapy Era

Osteoradionecrosis (ORN) of the mandible is the most devastating toxicity following head and neck cancer (HNC) radiotherapy (RT). The rate of ORN occurrence has been debatable in the modern era of advanced RT. We aim to determine the natural history and time to ORN development in a large cohort of HNC. After IRB approval, we identified HNC patients treated with curative-intent RT between 2005 and 2020 at MD Anderson Cancer Center. Dental oncology notes were reviewed and all dental procedures were recorded. Available dose volume histograms (DVHs) for the segmented mandibular volumes were extracted. Based on our previously published ORN normal tissue complication probability (NTCP) model, any dental procedure pre-RT is a clinical high-risk factor and, therefore, data were coded as (high vs. low clinical risk) accordingly. We also coded the dosimetric risk factors to (high vs. low dosimetric risk) according to our published DVH thresholds (high dosimetric risk if any applies: V45≥40%, V55≥25%, and/or D30 ≥40 Gy). Finally, patients were classified to four groups according to combined clinical and dosimetric risk factors (No, clinical, dosimetric, and both). We used the Kaplan-Meier method to calculate time to ORN development and ORN-free survival. For time to ORN development, any grade ORN occurrence was coded as event and all others were censored. For ORN-free survival, death and ORN were coded as events and all others were censored. Log-rank test was used to compared curves of different risk groups. One thousand eight hundred sixty-six patients were included. Median follow-up was 38 months (range 4-162). ORN was reported in 252 patients (13.5%). The median time to ORN development was 18.5 months (range 4-145). 95 patients (37.7%) developed ORN after 2-years post-RT. The 1-, 3-, and 5-year ORN rates were 4.7%, 12.7%, and 17.8%, respectively. The 1-, 3-, and 5-year ORN-free survival were 94.3%, 85.5%, and 80.3%, respectively. There were statistically significant differences (P < 0.0001) between ORN-free survival in different clinical/dosimetric risk factors. The patients with no, clinical-only, dosimetric-only, and both clinical and dosimetric risk factors were 35%, 19%, 22%, and 24%, respectively. The 5-year ORN-free survival was 94.3%, 89.8%, 76.3%, and 69.6% for patients with no, clinical-only, dosimetric-only, and both clinical and dosimetric risk factors, respectively. The hazard-ratio (HR) of ORN development in clinical-only, dosimetric-only, and both clinical and dosimetric risk groups was 2.1, 5.4, and 7.5 compared to the no risk group (P<0.05 for all). Our findings indicate that ORN remains a remarkable toxicity hazard for HNC survivors. A prolonged surveillance time is required for the majority of HNC survivor since more than one-third of the ORN events occurred after 2-year follow-up. Patients with combined clinical and dosimetric risk factors have a staggering ORN risk profile and are proper candidates for future prophylactic pharmacotherapy clinical studies.

Association of radiation dose to cardiac substructures with major ischaemic events following breast cancer radiotherapy.

Patients with left-sided breast cancer receive a higher mean heart dose (MHD) after radiotherapy, with subsequent risk of ischaemic heart disease. However, the optimum dosimetric predictor among cardiac substructures has not yet been determined. This study retrospectively reviewed 2158 women with breast cancer receiving adjuvant radiotherapy. The primary endpoint was a major ischaemic event. The dose-volume parameters of each delineated cardiac substructure were calculated. The risk factors for major ischaemic events and the association between MHD and major ischaemic events were analysed by Cox regression. The optimum dose-volume predictors among cardiac substructures were explored in multivariable models by comparing performance metrics of each model. At a median follow-up of 7.9 years (interquartile range 5.6-10.8 years), 89 patients developed major ischaemic events. The cumulative incidence rate of major ischaemic events was significantly higher in left-sided disease (P = 0.044). Overall, MHD increased the risk of major ischaemic events by 6.2% per Gy (hazard ratio 1.062, 95% confidence interval 1.01-1.12; P = 0.012). The model containing the volume of the left ventricle receiving 25 Gy (LV V25) with the cut-point of 4% presented with the best goodness of fit and discrimination performance in left-sided breast cancer. Age, chronic kidney disease, and hyperlipidaemia were also significant risk factors. Risk of major ischaemic events exist in the era of modern radiotherapy. LV V25 ≥ 4% appeared to be the optimum parameter and was superior to MHD in predicting major ischaemic events. This dose constraint could aid in achieving better heart protection in breast cancer radiotherapy, though a further validation study is warranted.

Abstract OT1-21-01: Preoperative radiotherapy and systemic therapy following surgery in ‘de novo’ metastatic breast cancer (Protocol MF22-01; Intervention Systemic Treatment METastasis-ISTMET)

Abstract Background Five to eight percent of breast cancer (BC) patients present with distant metastasis at diagnosis, known as ‘de Novo’ metastatic breast cancer (dnMBC). Recent data showed that approximately 40% of dnMBC patients undergo locoregional treatment (LRT). LRT treatment modalities for metastasis and primary tumor benefit a subset of patients with oligometastatic disease. Our study group has recently demonstrated two prospective studies regarding this topic with favorable outcomes. MF07-01 IMET study, one of the first clinical randomized trials, showed that the patients with the diagnosis of dnMBC undergoing LRT followed by systemic therapy had an additional 14% OS benefit by the end of the 10-year follow-up when compared with others who received only systemic therapy. A prospective multicenter registry study MF14-01 BOMET also presented LRT prolonged survival and decreased locoregional recurrence in a prospective registry study with a median follow-up of 3 years. Timing of primary breast surgery either at diagnosis or after systemic treatment provided a survival benefit similar to systemic therapy alone in bone-only dnMBC patients. Although, the optimal timing of concurrent endocrine therapy, radiotherapy, and/or sequential surgery remains unclear. Hypothesis We hypothesize that in the era of modern radiotherapy and endocrine therapy, concurrent radiation and endocrine therapy will be non-inferior to sequential treatment modalities in terms of locoregional and systemic disease control in dnMBC. ER/PR (+), Her2 neu (-) oligometastatic dnMBC patients are potentially curable with multimodality treatments. Objectives The primary objective is to perform a Phase I study to evaluate the feasibility of this curative intent treatment approach for patients with oligometastatic disease. Secondary objectives are to present the treatment response evaluating with CTC and/or ctDNA, and IHC and marker changes with multimodality treatments Methods Postmenopausal ER/PR (+) and Her2 neu (-), oligometastatic dnMBC patients will be enrolled in the study. Inclusion criteria: Primary breast tumor amenable for complete surgical resection, patients in good physical condition for receiving protocol-driven locoregional and systemic treatments and radiotherapy; Bone-only oligometastatic disease (5 or less metastasis); Primary tumor biopsy, metastatic site biopsy (ER/PR, Her2, Ki67). Exclusion criteria: Primary tumor not amenable for complete resection; primary tumor with extended infection, bleeding, or necrosis; patients with poor physical condition which prevents the patient from receiving protocol-driven locoregional and systemic treatment; synchronous primary cancer at the contralateral breast; clinically involved contralateral axillary nodes; patients not suitable for adequate follow-up, and failure to give informed consent. Study Design: • RT to the primary tumor (Hypo fractionated) + AI concurrent, Collect CTC and/or ctDNA • Add CDK4/6i to AI 2-4 weeks after RT + (6 months) • RT to bone metastasis (if still visible), Collect CTC and/or ctDNA + (12 months) • Primary Breast Surgery, Collect CTC and/orctDNA, ER/PR/Her 2 in the final specimen + • CDK4/6i +AI until progression and/or unmanageable toxicity Conclusion We hypothesize that in the era of modern radiotherapy and endocrine therapy, concurrent radiation and endocrine therapy will be non-inferior to sequential treatment modalities in terms of locoregional and systemic disease control in dnMBC. ER/PR (+), Her2 neu (-) oligometastatic dnMBC patients are potentially curable with multimodality treatments. Citation Format: Atilla Soran, Serdar Ozbas, Lutfi Dogan, Kamuran İbis, Mutlu Dogan, M Selam, Kazim Senol, Secil Ak Aksoy, Mine Ozsen, Sibel Cetintas, Turkkan Evrensel, Efe Sezgin. Preoperative radiotherapy and systemic therapy following surgery in ‘de novo’ metastatic breast cancer (Protocol MF22-01; Intervention Systemic Treatment METastasis-ISTMET) [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT1-21-01.

Radiation-induced lung injury - what do we know in the era of modern radiotherapy?

Radiation-induced lung injury (RILI) that is usually divided into an early radiation-induced pneumonitis (RIP) and late chronic radiation-induced lung fibrosis (RILF) remains a clinically significant toxicity in radiation oncology. Thus, a thorough understanding of underlying molecular mechanisms and risk factors is crucial. This review, focused on patients treated with modern radiotherapy (RT) techniques, describes the different clinical presentations of RIP, with most typical imaging findings and usefulness of pulmonary function tests and laboratory assessment in differential diagnosis. The most critical patient- and treatment-related predictors are summarized and discussed — age and sex, comorbidities, tumour characteristics, concomitant treatment, and RT-plan parameters. The conventional grading scales and contemporary approach to quantitative assessment (radiomics, CT density changes) is described as well as treatment methods.

PO-0963 How to optimize prognosis prediction of nasopharyngeal carcinoma in the era of modern radiotherapy?

PO-0963 How to optimize prognosis prediction of nasopharyngeal carcinoma in the era of modern radiotherapy?

Limited recurrence distance of glioblastoma under modern radiotherapy era

BackgroundThe optimal treatment volume for Glioblastoma multiforme (GBM) is still a subject of debate worldwide. The current study was aimed to determine the distances between recurring tumors and the edge of primary lesions, and thereby provide evidence for accurate target area delineation.MethodsBetween October 2007 and March 2019, 68 recurrent patients with GBM were included in our study. We measured the distance from the initial tumor to the recurrent lesion of GBM patients by expanding the initial gross tumor volume (GTV) to overlap the center of recurrent lesion, with the help of the Pinnacle Treatment Planning System.ResultsRecurrences were local in 47(69.1%) patients, distant in 12(17.7%) patients, and both in 9(13.2%) patients. Factors significantly influencing local recurrence were age (P = 0.049), sex (P = 0.049), and the size of peritumoral edema (P = 0.00). A total number of 91 recurrent tumors were analyzed. All local recurrences occurred within 2 cm and 94.8% (55/58) occurred within 1 cm of the original GTV based on T1 enhanced imaging. All local recurrences occurred within 1.5 cm and 98.3%(57/58) occurred within 0.5 cm of the original GTV based on T2-FLAIR imaging. 90.9% (30/33) and 81.8% (27/33) distant recurrences occurred >3 cm of T1 enhanced and T2-Flair primary tumor margins, respectively.ConclusionsThe 1 cm margin from T1 enhanced lesions and 0.5 cm margin from T2-Flair abnormal lesions could cover 94.8 and 98.3% local recurrences respectively, which deserves further prospective study as a limited but effective target area.

Multidisciplinary Management of Radiation-Induced Salivary Gland Carcinomas in the Modern Radiotherapy Era.

Simple SummaryEtiopathogenesis of salivary gland cancers [SGCs] is largely unknown, even if exposition to ionizing radiation is a recognized risk factor for SGCs development. To date, exhaustive data to guide clinicians in managing patients with radiation-induced [ri] SGCs are scarce and their treatment remains challenging. The purpose of this work is to describe and to analyze clinical and histopathological features, delivered treatments, and outcome of a series of patients with ri-SGCs treated at two Italian cancer referral sites. Given the rarity of ri-SGCs, this retrospective analysis conducted on a case series of 13 patients adds further knowledge to the paucity of literature. The management of these malignancies is extremely complex requiring a multidisciplinary treatment approach.Clinical data of ri-SGCs patients treated between 2015 and 2019 at a tertiary cancer center and a national hadron therapy facility were reviewed. Latent time (LT) from first RT to ri-SGCs diagnosis, overall (OS), and disease-free survival (DFS) were assessed. Thirteen patients developed 14 ri-SGCs (one patient had 2 synchronous ri-SCGs), after a median LT of 23 years (range 16–34). Parotid was the primary site in 8 cases (57%) and salivary duct carcinoma was the most frequent histotype (29%). Nine patients (69%) underwent surgery (Sx). Among them, 4 patients (31%) underwent Sx alone, 5 received post-operative treatments: 3 (23%) photon-based (X) reRT, one (8%) protons and carbon ions, one (8%) carbon ions only. One patient (8%) received definitive XRT. The remaining 3 patients (23%) received androgen deprivation therapy. With a median follow-up of 48 months (range 24–72), median OS and PFS were 74 and 24 months, respectively. In the subgroup of AR+ ri-SGCs, median PFS and OS were 12 and 74 months, respectively. Given the rarity of ri-SGCs, this work adds further knowledge to the paucity of literature. The management of these malignancies is extremely complex requiring a multidisciplinary treatment approach.

The Risk of Second Primary Cancers in Prostate Cancer Survivors Treated in the Modern Radiotherapy Era.

PurposeConcerns have been raised that modern intensity modulated radiotherapy (IMRT) may be associated with increased second primary cancer risks (SPC) compared to previous three-dimensional conformal radiation techniques (3DCRT), due to increased low dose volumes and more out-of-field ionizing dose to peripheral tissue further away from the target. We assessed the impact of treatment technique on SPC risks in a cohort of prostate cancer (PCa) survivors.Material and MethodsThe study cohort comprised 1,561 PCa survivors aged 50–79 years at time of radiotherapy, treated between 2006–2013 (N=707 IMRT, N=854 3DCRT). Treatment details were extracted from radiotherapy systems and merged with longitudinal data of the Netherlands Cancer Registry to identify SPCs. Primary endpoint was the development of a solid SPC (excluding skin cancer) in peripheral anatomical regions, i.e. non-pelvic. Applied latency period was 12 months. SPC rates in the IMRT cohort (total cohort and age subgroups) were compared to 1) the 3DCRT cohort by calculating Sub-Hazard Ratios (sHR) using a competing risk model, and 2) to the general male population by calculating Standardized Incidence Ratios (SIR). Models were adjusted for calendar period and age.ResultsMedian follow-up was 8.0 years (accumulated 11,664 person-years at-risk) with 159 cases developing ≥1 non-pelvic SPC. For IMRT vs 3DCRT we observed a significantly (p=0.03) increased risk (sHR=1.56, 95% Confidence Interval (CI) 1.03–2.36, corresponding estimated excess absolute risk (EAR) of +7 cases per 10,000 person-years). At explorative analysis, IMRT was in particular associated with increased risks within the subgroup of active smokers (sHR 2.94, p=0.01). Within the age subgroups 50–69 and 70–79 years, the sHR for non-pelvic SPC was 3.27 (p=0.001) and 0.96 (p=0.9), respectively. For pelvic SPC no increase was observed (sHR=0.8, p=0.4). Compared to the general population, IMRT was associated with significantly increased risks for non-pelvic SPC in the 50–69 year age group (SIR=1.90, p<0.05) but not in the 70–79 years group (SIR=1.08).ConclusionIMRT is associated with increased SPC risks for subjects who are relatively young at time of treatment. Additional research on aspects of IMRT that may cause this effect is essential to minimize risks for future patients receiving modern radiotherapy.

Radical external beam re-irradiation in the treatment of recurrent head and neck cancer: Critical review.

Management of patients with recurrent head and neck cancer remains a challenge for the surgeon as well as the treating radiation oncologist. Even in the era of modern radiotherapy, the rate of severe toxicity remains high with unsatisfactory treatment results. Intensity-modulated radiation therapy (IMRT), stereotactic body radiation therapy (SBRT), and heavy-ion irradiation have all emerged as highly conformal and precise techniques that offer many radiobiological advantages in various clinical situations. Although re-irradiation is now widespread in clinical practice, little is known about the differences in treatment response and toxicity using diverse re-irradiation techniques. In this review, we provide a comprehensive overview of the role of radiation therapy in recurrent or second primary head and neck cancer including patient selection, therapeutic outcome, and risk using different re-irradiation techniques. Critical review of published evidence on IMRT, SBRT, and heavy-ion full-dose re-irradiation is presented including data on locoregional control, overall survival, and toxicity.

Impact of adjuvant radiotherapy on the survival of women with optimally resected stage III endometrial cancer in the era of modern radiotherapy: a retrospective study

BackgroundThe optimal adjuvant treatment for stage III endometrial cancer in the era of modern radiotherapy remains undefined. We investigated the benefit of adjuvant radiotherapy for women who underwent optimal resection for stage III endometrial cancer in the era of modern radiotherapy.MethodsWe retrospectively reviewed patients with endometrial cancer who were treated between 2010 and 2018. Adjuvant treatment included radiotherapy by modern radiotherapy techniques (intensity-modulated or volumetric modulated arc radiotherapy), chemotherapy, or both. Recurrence-free survival (RFS) and overall survival (OS) were calculated using the Kaplan-Meier method and analyzed via multivariate Cox proportional hazards models.ResultsOne hundred sixty-one patients were initially included (52, 9, and 100 with stages IIIA, IIIB, and IIIC cancer, respectively); 154 patients (96%) received adjuvant therapy. Such adjuvant treatment was associated with improved RFS (p = 0.014) and OS (p = 0.044) over surgery alone. Adjuvant radiotherapy by modern radiotherapy techniques led to low incidence of acute (25%) and chronic (7%) grade ≥ 2 gastrointestinal toxicity. On univariate analysis, non-endometrioid histology and grade 3 status were associated with higher risks of tumor recurrence and death, whereas adjuvant radiotherapy alone or in combination chemotherapy reduced their risks. On multivariate analysis, non-endometrioid histology was associated with increased recurrence (hazard ratio [HR], 2.95; p = 0.009), whereas adjuvant radiotherapy alone or with chemotherapy was associated with lower recurrence (HR, 0.62; p = 0.042). Patients > 60 years of age (p = 0.038) as well as those with endometrioid histology (p = 0.045), lymphovascular space invasion (p = 0.031), and ≥ 2 positive lymph nodes (p = 0.044) benefited most from adjuvant radiotherapy.ConclusionsModern adjuvant radiotherapy (intensity-modulated or volumetric modulated arc radiotherapy) alone or with chemotherapy should be considered for women with optimally resected stage III endometrial cancer.Trial registrationClinicalTrials.gov, NCT04251676. Registered 24 January 2020. Retrospectively registered.

Implantation of tissue expander prior to irradiation in the era of intensity modulated radiotherapy: impact on the management of patients with pelvic digestive cancers.

Before the introduction of intensity-modulated radiation therapy (IMRT), few teams used to implant a pelvic tissue expander to keep the bowel away from the radiation field, so as to reduce the risk of acute and late enteritis. However, this unexpected surgery could impact patient's overall treatment and may be no more necessary in the era of modern radiotherapy. This is a retrospective cross-sectional study including 13 patients who underwent tissue expander implantation before radiotherapy or chemoradiotherapy for rectal or anal carcinoma between November 2008 and March 2019. First, we aim to show that IMRT could sometimes be insufficient to respect dosimetric constraints, and then we aim to report the impact of tissue expander implantation on the global strategy of care of patients with anal and rectal cancers. Seventy-seven percent of the included patients were treated for anal neoplasms, while the remaining 23% had locally advanced rectal cancer. The median follow-up since implantation of the expander was 51months [3.7-115]. Three patients recurred. One patient developed grade III toxicity related to the implantation of a tissue expander. The delay between diagnosis and the start of irradiation was significantly prolonged (median of 3months), requiring unusual induction chemotherapy. Implantation of tissue expander prior to chemoradiotherapy should be considered, even in the era of IMRT, when irradiated peritoneal cavity volume (V15Gy-V45Gy) far exceeds usual dose constraints. However, it impacts the global strategy of care by delaying the start of irradiation, by introducing induction chemotherapy, and rarely by causing post-operative complications.

Chest wall recurrence in pT1-2N0-1 breast cancer patients after mastectomy without radiotherapy.

In correlation with the nodal status in the era of modern radiotherapy, the chest wall recurrence (CWR) rate was investigated in pT1-2N0-1 breast cancer patients after a mastectomy without post-mastectomy radiotherapy (PMRT). The data from the patients participating in two South Korean multi-institutional studies (KROG 14-22; N=1842 and KROG 14-23; N=1382) were analyzed. In total, 3224 pT1-2N0-1 breast cancer patients who underwent mastectomy without PMRT were analyzed. The median follow-up time was 72.2months (range 0.8-125.2months). The overall CWRs during the follow-up period were 1.68% in N0 patients and 2.82% in N1 patients. There was no statistically significant difference in 5-year and 10-year CWR-free survival (CWRFS) between the N0 and N1 patients. Of the 70 patients with CWR, 33 (1% of all the patients) had isolated CWR, and the 10-year overall survival rate in this group was 96.9%. After the propensity score matching of the N0 and N1 groups, there was still no difference in CWRFS by nodal status. The incidence of CWR in pT1-2N0-1 breast cancer patients is very low, especially with isolated recurrence. Also, the obtained data showed that the nodal status had no impact on CWRFS.

Definitive salvage for vaginal recurrence of endometrial cancer: The impact of modern intensity-modulated-radiotherapy with image-based HDR brachytherapy and the interplay of the PORTEC 1 risk stratification

PurposeData for salvage radiotherapy for recurrent endometrial cancer are limited especially in the era of modern radiotherapy including IMRT and 3-dimensional image-based HDR brachytherapy. Theoretically, modern radiotherapy reduces the dose to critical organs-at-risk and maximizes dose to the target volume, possibly decreasing morbidity and increasing tumor control. Materials and methodsForty-one patients completing definitive salvage radiotherapy for vaginal recurrence of endometrial cancer from June 2004 to December 2013 were retrospectively reviewed. HDR Brachytherapy was completed using image-based planning with contouring/optimization with each fraction to a median dose of 23.75Gy in 5 fractions. HDR brachytherapy was preceded by external beam radiotherapy predominately using an IMRT technique (90%) to a median dose of 45Gy in 25 fractions. Toxicity was reported according to CTCAEv4. ResultsAt a median follow-up of 18months (range: 3–78), the clinical complete response rate was 95%. The 3-year local control, distant control, recurrence free survival, and overall survival were 95%, 61%, 68%, and 67%. Significant predictors of both distant failure and overall survival were primary prognostic factors of depth of myometrial invasion, FIGO stage, and FIGO grade. There was no grade 3+ acute toxicity; the 3-year rate of grade 3+ late toxicity was 8%. ConclusionsSalvage IMRT plus 3-dimensional image-based HDR brachytherapy shows excellent tumor control and minimal morbidity for vaginal recurrence of endometrial cancer. Anticipated salvage rates must be taken in the context of primary risk factors including depth of myometrial invasion, FIGO stage, and FIGO grade.

Difficult Wounds: Radiation Wounds

In an era of modern radiotherapy, problems associated with the indiscriminate treatment of benign disease have largely disappeared. Skin sparing effects of super voltage radiation equipment make the problems previously seen with orthovoltage equipment less frequent. Vigilance on the part of the workers in the field, in general, protects from the disasters that befell Thomas Edison's laboratory assistant. Despite these modern advances, the reconstructive surgeon often faces problems of managing acute local radiation injury from accident following planned therapeutic radiation or the ulcerations and breakdowns seen months or years after radiation therapy. The single most serious hazard to surgery in radiated tissue is the lodgment of bacteria in this tissue rendered avascular by the radiation and secondary necrosis from the infection itself. The principles of management are no different from those used for other chronic granulating wounds: local wound care, appropriate topical antibacterial therapy, systemic antibiotics during the perioperative period and, most importantly, adequate soft tissue coverage.