Riesgo de osteorradionecrosis de los maxilares según el tipo de radioterapia / Risk of Osteoradionecrosis of the Jaws according to Type of Radiotherapy

Introducción: El cáncer de cabeza y cuello es el séptimo más común a nivel mundial. Las opciones terapéuticas para su manejo incluyen la radioterapia, la cual debe procurar un equilibrio entre la eliminación del tumor y la preservación del tejido sano porque su aplicación implica el riesgo de desarrollar una osteorradionecrosis de los maxilares. Objetivo: Valorar si el riesgo de que se produzca osteorradionecrosis de los maxilares varía en función del tipo de radioterapia. Métodos: Diseño documental, retrospectivo basado en los principios de las revisiones sistemáticas exploratorias según lo establece la lista de chequeo PRISMA Extension for Scoping Reviews (PRISMA-ScR). Se realizaron búsquedas en inglés y español en PubMed, LILACS, ScienceDirect, Tripdatabase y Epistemonikos. Resultados: En total se incluyeron 12 estudios publicados entre 2016 y 2022 con diversos diseños de investigación; el estudio de cohorte retrospectivo fue el que tuvo mayor representación. Se analizaron distintas opciones de radioterapia y sus protocolos, entre ellos, la radioterapia de intensidad modulada, la terapia de protones de intensidad modulada, la radioterapia corporal estereotáctica y la radioterapia tridimensional. La literatura refiere que los protocolos que implican dosis totales más bajas representan un menor riesgo de osteorradionecrosis. Conclusiones: El riesgo de osteorradionecrosis de los maxilares debe atribuirse, en mayor medida, a la dosis total de radiación recibida por el paciente y a la dosis por fracción que al tipo de radioterapia(AU)

Introduction: Head and neck cancer is the seventh most common cancer worldwide. Therapeutic options for its management include radiotherapy, which should seek a balance between tumor elimination and preservation of healthy tissue because its application implies the risk of developing osteoradionecrosis of the jaws. Objective: To assess whether the risk of developing osteoradionecrosis of the jaws varies according to the type of radiotherapy. Methods : Documentary, retrospective design based on the principles of exploratory systematic reviews as established by the PRISMA Extension for Scoping Reviews (PRISMA-ScR) checklist. PubMed, LILACS, ScienceDirect, Tripdatabase and Epistemonikos were searched in English and Spanish. Results: In total, 12 studies published between 2016 and 2022 with various research designs were included; the retrospective cohort study had the highest representation. Different radiotherapy options and their protocols were analyzed, including intensity-modulated radiotherapy, intensity-modulated proton therapy, stereotactic body radiotherapy, and three-dimensional radiotherapy. The literature refers that protocols involving lower total doses represent a lower risk of osteoradionecrosis. Conclusions: The risk of osteoradionecrosis of the jaws should be attributed, to a greater extent, to the total radiation dose received by the patient and the dose per fraction than to the type of radiotherapy(AU)

A incidência de osteorradionecrose em pacientes com câncer de cavidade oral tratados por radioterapia de intensidade modulada (IMRT): uma revisão sistemática e meta-análise / The incidence of osteoradionecrosis in oral cavity cancer patients treated with intensity-modulated radiotherapy (IMRT): a systematic review and meta-analysis

Os valores de incidência de osteorradionecrose dos maxilares reportados ao longo das últimas décadas variaram. Nos estudos que reportam baixos valores de incidência de osteorradionecrose através do uso de técnicas de radioterapia, que começaram a entregar altas dose de radiação ao volume tumoral alvo poupando tecidos circunjacentes sadios, os cânceres de cavidade oral frequentemente estão atrelados a maior parte dos casos, tornando a realidade dos resultados de incidência contraditórios, uma vez que a presença de coortes mistas, com cânceres em diferentes localizações de cabeça e pescoço, dão poucos ou nenhum dado específico para os pacientes com câncer de cavidade oral. Com o objetivo de avaliar a incidência de osteorradionecrose em pacientes com câncer de cavidade oral tratados com a radioterapia de intensidade modulada e os fatores de risco que influenciam no desenvolvimento e subsequentemente, a incidência culmulativa de osteorradionecrose, foi realizada uma revisão sistemática com meta-análise da literatura registrada na plataforma preferenciais para revisão sistemática e metanálise sob o registro de protocoloco CRD42021295524. Inicialmente foram elaboradas estratégias de buscas para seis bases de dados, que resultaram em 884 artigos, posteriormente transportados para o aplicativo online Rayyan® para a primeira seleção. Após a exclusão de 200 duplicatas, 689 registros foram avaliados por título e resumo, sendo eleitos para análise completa do texto, 87. Por fim, 11 estudos foram incluídos para a síntese qualitativa e desses, 6 foram incluídos também para a síntese quantitativa. Em 1.434 pacientes com câncer de cavidade oral tratados por radioterapia de intensidade modulada, 150 desenvolveram osteorradionecrose. A incidências brutas individuais dos estudos variaram de 0 a 20,7%, com tempo médio entre o fim da radioterapia e o diagnóstico de osteorradionecrose de 31,7±9,7 meses em um acompanhamento médio de 46,2±13,1 meses. Os fatores mais correlacionados ao desenvolvimento da osteorradionecrose foram cirurgia préradioterapia (12%), tumores localizados em assoalho bucal ou língua (4%), carcinoma de células escamosas (42%) e mandíbula (80%). A meta-análise dos 6 estudos revelou a incidência acumulada de 8% (I2 = 0%, t2 = 0, p = 0,84). Oito dos 11 artigos incluídos tiveram o risco de viés avaliados como moderado e três como baixo. Podemos concluir que a radioterapia de intensidade modulada foi efetiva na preservação dos ossos da mandíbula e maxila que resultou em um baixo índice de incidência de osteorradionecrose em um sítio de alto risco como a cavidade oral. (AU)

The reported incidence values of jaw osteoradionecrosis have varied over the past decades. In studies reporting low incidence rates of osteoradionecrosis through the use of radiotherapy techniques that started delivering high radiation doses to the target tumor volume while sparing surrounding healthy tissues, oral cavity cancers are often associated with the majority of cases. This has led to contradictory incidence results, as the presence of mixed cohorts, with cancers in different head and neck locations, provides limited to no specific data for patients with oral cavity cancer. In order to assess the incidence of osteoradionecrosis in oral cavity cancer patients treated with intensity-modulated radiotherapy and the risk factors influencing its development and subsequent cumulative incidence, a systematic review with meta-analysis of the literature registered in the preferred platform for systematic review and meta-analysis under protocol registration CRD42021295524 was conducted. Initially, search strategies were developed for six databases, resulting in 884 articles, which were subsequently imported into the online Rayyan® application for the initial selection. After excluding 200 duplicates, 689 records were evaluated by title and abstract, with 87 selected for full-text analysis. Finally, 11 studies were included for qualitative synthesis, and of those, 6 were also included for quantitative synthesis. Among 1,434 oral cavity cancer patients treated with intensity-modulated radiotherapy, 150 developed osteoradionecrosis. Individual raw incidence rates in the studies ranged from 0 to 20.7%, with a mean time between the end of radiotherapy and osteoradionecrosis diagnosis of 31.7±9.7 months in an average follow-up of 46.2±13.1 months. The factors most correlated with osteoradionecrosis development were preradiotherapy surgery (12%), tumors located in the floor of the mouth or tongue (4%), squamous cell carcinoma (42%), and mandibular involvement (80%). Meta-analysis of the 6 studies revealed a cumulative incidence of 8% (I2 = 0%, t2 = 0, p = 0.84). Eight of the 11 included articles had their bias risk assessed as moderate, and three as low. In conclusion, intensity-modulated radiotherapy was effective in preserving the jaw and maxilla bones, resulting in a low incidence of osteoradionecrosis in a high-risk site like the oral cavity (AU)

Pineal germinoma in a young adult: A case report.

BACKGROUND: Intracranial germinomas (GN) are rare cancers that primarily affect children, making them rarer still in adults. Standard treatment for this neoplasm includes neoadjuvant chemotherapy (NC) followed by radiotherapy (RT) or RT at a higher dose and larger field. These recommendations are based on studies focused mostly on children; it is currently unclear whether this treatment is applicable to adults. CASE: We present a case of a 23-year-old adult male with no underlying pathologies, drug allergies, or family history of cancer, who presented for medical evaluation with blurred vision, diplopia, forgetfulness, and weight loss starting 3-4 months before the evaluation. Clinical examination indicated Parinaud's Syndrome. Magnetic resonance imaging (MRI) and computed tomography (CT) revealed a pineal tumor with ependymal dissemination in both lateral ventricles, which was causing obstructive hydrocephalus. The patient had surgery consisting of ventriculostomy, Holter shunt insertion, cisternal ventricular intubation, and cisterna magna anastomosis to improve ventricular drainage. Pathology confirmed pineal germinoma. Cerebrospinal fluid cytology and MRI of the axis were negative. Four cycles of NC were given to the patient (carboplatin, etoposide, and ifosfamide), with reduced dosage. Once a partial volumetric response was confirmed, whole-ventricular radiotherapy (WVR) was initiated with a total tumor bed dose of 45 Gy over 25 sessions in 5 weeks. Optimum clinical results were observed, and no short-term (<90 day) radiation toxicity was observed. The patient was able to resume his normal activities soon after treatment. Follow-ups over 2 years post-surgery indicated continued control of the lesion and absence of symptoms except for mild diplopia. CONCLUSION: Although this is a case report, these data suggest that a reduced NC course and WVR may effectively treat adult GN. This protocol likely decreases the risk of undesirable NC and RT secondary effects, while providing excellent local control; however, using a narrower RT field is not recommended.

Micro-CT analysis of the mandibular bone microarchitecture of rats after radiotherapy and low-power laser therapy.

To investigate whether low-level laser therapy (LLLT), at different times of application (immediate and late) in the region of the parotid glands, has a distance effect on the microarchitecture of the trabecular bone in mandible of rats irradiated by volumetric modular arc therapy (VMAT). Thirty adult Wistar rats were randomly divided into placebo control groups (CG, n = 2), only radiotherapy (RG, n = 2), only LPLT (LG, n = 2), and two other groups using LLLT in the immediate time (24 h) (ILG, n = 12) and late (120 h) (LLG, n = 12) to radiotherapy by VMAT in a single dose of 12 Gy. LLLT with AsGaAl laser (660 nm, 100 mW), a spot size of 0.0028 cm2, was applied in three points in the region of the right parotid gland, with energy of 2 J/cm2, 20 s per point, for 10 consecutive days. After euthanasia, the right hemimandibles of each animal were dissected, prepared, and analyzed by computerized microtomography (micro-CT) and histomorphometry. The different groups were analyzed by the Tukey and Bonferroni multiple comparison tests. The micro-CT analysis found statistically significant differences between the groups, especially in the LLG, which had the highest average bone volume compared to the CG (p = 0.001) and ILG (p = 0.002) and a greater number of trabeculae than the CG (p = 0.000) and ILG (p = 0.031). The ILG also had a higher number of trabeculae than the CG (p = 0.005). Trabecula separation (Tb.Sp) was lower in the LLG (p = 0.000) and ILG (p = 0.002) when compared to the CG. In the histomorphometry, there was no statistical difference between the groups in relation to all the analyzed variables. Micro-CT analysis showed that the LLLT, even applied at a distance, both in the immediate and late VMAT times, has an effect on the mandibular bone microarchitecture by increasing the volume and number of trabeculae and decreasing the spaces between them.

Effect of tumor and normal lung volumes on the lung volume-dose parameters of IMRT in non-small-cell lung cancer

OBJECTIVES: To explore the effect of tumor and normal lung volumes on lung volume-dose parameters in patients with non-small-cell lung cancer (NSCLC) who had undergone intensity-modulated radiation therapy (IMRT). METHODS: The clinical data of 208 patients with NSCLC who underwent radical IMRT between June 2014 and June 2018 were retrospectively analyzed. A regression model curve was used to evaluate the effect of tumor and normal lung volumes on normal lung relative volumes receiving greater than 5 and 20 Gy (V5, V20), on mean lung dose (MLD), and on absolute volumes spared from greater than 5 and 20 Gy (AVS5, AVS20). RESULTS: The V5, V20, and MLD of the bilateral lung were fitted to a quadratic equation curve with the change in tumor volume, which increased initially and then decreased when the tumor volume increased. The V5, V20, and MLD of the lung reached their apex when the tumor volumes were 288.07, 341.69, and 326.83 cm3, respectively. AVS5 and AVS20 decreased in a logarithmic curve with an increase in tumor volume. The V5, V20, and MLD of the small normal lung volume group were all significantly higher than those of the large normal lung volume group (p<0.001, p=0.004, p=0.002). However, the AVS5 and AVS20 of the small normal lung volume group were all significantly lower than those of the large normal lung volume group (p<0.001). CONCLUSION: The effects of tumor volume and normal lung volume on dose-volume parameters should be considered. AVS5 is an important supplementary dose limitation parameter for patients whose tumor volume exceeds a certain boundary value (approximately 300 cm3).

Locoregional control and toxicity after pleurectomy/decortication and intensity-modulated pleural radiation therapy in patients with malignant pleural mesothelioma.

BACKGROUND: Treatment of malignant pleural mesothelioma (MPM) represents a major challenge for oncologists. Multimodality treatment, which generally involves induction chemotherapy, surgery and radiotherapy have recently shown promising results. The aim of this study was to evaluate the locoregional control and toxicity of intensity modulated radiotherapy (IMRT) after pleurectomy and decortication (P/D) as part of trimodality therapy for patients with locally advanced MPM. METHODS: We prospectively analyzed data from 20 patients with MPM treated at a single tertiary-care institution. Initially every patient received induction chemotherapy with platinum-based chemotherapy. After chemotherapy, patients without progression underwent P/D, and if feasible, hemi-thoracic IMRT was administered at a planned dose of 50.4-54 Gy in 28-30 fractions and treated with 9-11 noncoplanar fields. RESULTS: A total of 15 of the 20 enrolled patients underwent P/D followed by IMRT to the hemi-thoracic cavity. The median total radiotherapy dose was 48.7 Gy (23.4-54 Gy). Radiation pneumonitis (RP) developed in nine patients (60%), and of these, two patients (13.3%) experienced G3 or G4 RP. The estimated locoregional-relapse-free survival at two years was 75.9%, and the main pattern of recurrence was distant (72.7%). For the entire cohort median follow-up was 22.7 months, median progression-free survival was 18.9 months and median overall survival 23.6 months. CONCLUSIONS: Platinum-based chemotherapy followed by lung-sparing surgery (P/D) and IMRT is a feasible and safe treatment modality that yields acceptable locoregional control in patients with locally advanced MPM; however, these results should be corroborated in larger studies.

Evaluation of Aquaporins 1 and 5 Expression in Rat Parotid Glands After Volumetric Modulated Arc Radiotherapy and Use of Low-Level Laser Therapy at Different Times.

Introduction: This experimental study investigated the mRNA expression of aquaporins (AQPs) 1 and 5 in the parotid glands of rats irradiated with volumetric modulated arc therapy (VMAT) and subjected to low-level laser therapy (LLLT) at different time points. Methods: The sample consisted of 30 Wistar rats (Rattus norvegicus) divided into the following groups: control, LLLT alone (LG), radiotherapy alone (RG), and experimental groups that received LLLT at 24 hours (early experimental group [EEG], n=12) and 120 hours (late experimental group [LEG], n=12) after radiotherapy. VMAT was delivered at a single dose (12 Gy) and LLLT was performed with an aluminium-gallium-arsenide diode laser (660 nm, 100 mW), spot area of 0.0028 cm2, energy of 2 J/cm2 applied to 3 spots in the region corresponding to the right parotid gland, for 10 consecutive days. The right parotid gland was resected and prepared for RNA extraction. The gene expression of AQPs was evaluated by quantitative polymerase chain reaction (qPCR) using specific TaqMan probes, with the HPRT gene as an internal control. Results: The lowest AQP1 gene expression was 0.83 (0.27) with the use of LLLT 24 hours after radiotherapy (EEG), and the highest was 1.56 (0.80) with the use of LLLT alone (LG). Likewise, the lowest AQP5 gene expression was found in the EEG (mean = 0.88; SD = 0.49) and the highest in the LG (mean = 1.29; SD = 0.33). Conclusion: The use of LLLT after radiotherapy may contribute to the maintenance and an increase of these proteins, even when used at a later time point after radiotherapy.

Significant impact on the oncologic outcomes with intensity modulated radiotherapy and conformational radiotherapy over conventional radiotherapy in cervix cancer patients treated with radiotherapy.

OBJECTIVE: We designed a retrospective cohort of women with cervix cancer treated by radiation therapy with an extended follow-up to evaluate if the incorporation of modern radiation techniques was a prognostic factor. MATERIAL AND METHODS: We studied a cohort of patients with cervix cancer FIGO stage I-IVa treated in the last fifteen years. Patients were treated with radiotherapy alone (RT) or chemoradiation alone (CRT) using conventional radiotherapy (2DRT), conformational radiotherapy (3DRT), or intensity-modulated radiotherapy (IMRT) followed by high dose rate brachytherapy. Univariate and multivariate analysis was conducted to identify significant prognostic factors (p < 0.05). RESULTS: 228 patients with cervix cancer were included. The treatment groups were CRT (64.8%), and RT (34.2%), with 31.6% submitted to 2DRT and 68.4% to IMRT/3DRT. The median follow-up was 6.3 years, the OS in 5 years according to the treatment groups was 48% for CRT, and 27.8% for RT (p < 0.001). The early-stage I-IIa (p = 0.001), CRT, and IMRT/3DRT were significant factors for better overall survival (OS) in the multivariate analysis. For the cancer-specific survival (CSS), chemoradiation, age <60 years, and IMRT/3DRT were significant. Treatment with IMRT/3DRT was the only prognostic factor associated with event-free survival (EFS). CONCLUSION: In a long-term follow-up, chemoradiation, early-clinical stage, and age <60 years were significant factors associated with better OS and CSS at 5 and 8 years. The incorporation of new radiation techniques, such as IMRT/3DRT, over time has a significant impact on all endpoints (EFS, OS, and CSS) of this cohort. These outcomes are useful to decide about the radiation technique to achieve satisfactory oncological results outside a clinical trial.

Transitioning from conformal radiotherapy to intensity-modulated radiotherapy after radical prostatectomy: Clinical benefit, oncologic outcomes and incidence of gastrointestinal and urinary toxicities.

AIM: The purpose of this study was to review genitourinary (GU) and gastrointestinal (GI) toxicity associated with high-dose radiotherapy (RT) delivered with 3-dimensional conformal radiotherapy (3D-CRT) and intensity-modulated radiotherapy (IMRT) or volumetric arc therapy (VMAT) following radical prostatectomy (RP). BACKGROUND: RP is a therapeutic option for the management of prostate cancer (PrCa). When assessing postoperative RT techniques for PrCa, the published literature focuses on patients treated with 2-dimensional conventional methods without reflecting the implementation of 3D-CRT, IMRT, or VMAT. MATERIALS AND METHODS: A total of 83 patients were included in this analysis; 30 patients received 3D-CRT, and 53 patients received IMRT/VMAT. Acute and late symptoms of the GU and lower GI tract were retrospectively graded according to the Radiation Therapy Oncology Group and the European Organization for Research and Treatment of Cancer radiation toxicity grading systems. The relapse failure-free rate and overall survival were also evaluated. RESULTS: The rate of acute GU toxicity was 9.4% vs. 13.3% for the IMRT/VMAT and 3D-CRT groups (p = 0.583). The 5-year actuarial rates of late GI toxicity for IMRT/VMAT and 3D-CRT treatments were 1.9% and 6.7%, respectively. The rate of late GU toxicity for the IMRT/VMAT and 3D-CRT treatment groups was 7.5% and 16.6%, respectively (p = 0.199). We found no association between acute or late toxicity and the RT technique in univariate and multivariate analyses. CONCLUSION: Postprostatectomy IMRT/VMAT and 3D-CRT achieved similar morbidity and cancer control outcomes. The clinical benefit of highly conformal techniques in this setting is unclear although formal analysis is needed.

Outcome and toxicity of intensity-modulated radiotherapy with simultaneous integrated boost in patients with pharyngo-laryngeal cancer.

PURPOSE: The present work aims at evaluating intensity-modulated radiation therapy with simultaneous integrated boost (IMRT-SIB) in squamous cell carcinomas (SCC) of the larynx and hypopharynx. METHODS/PATIENTS: We performed a single institutional retrospective analysis on 116 pharyngo (29%)-laryngeal (71%) SCC patients (93% male) treated with IMRT-SIB to 66-69.96 Gy in 33 fractions between 2008 and 2016. Those who underwent surgery (54%) received adjuvant radiation of 66 Gy at 2 Gy/fraction to the surgical bed. 16 patients (14%) were treated for a local recurrence after prior surgery. High-risk lymph node regions received 59.4 Gy at 1.8 Gy/fraction and low risk regions 54.12 Gy at 1.64 Gy/fraction. The median age was 60 years and 95% of patients had an ECOG performance status 0-2. Most had advanced stage disease (III 22%, IV 74%). Chemotherapy was delivered in 74% of cases. RESULTS: Median follow-up was 32 months. Two and three-year overall survival for all patients was 87% and 82%, respectively. There were 28 (24%) locoregional recurrences and 19 (16%) distant failures. Grade 3 mucositis, dermatitis, and xerostomy were observed in 12%, 10%, and 3%, respectively. A longer IMRT-SIB overall treatment time was associated with a higher risk of mortality (HR 1.09, CI 1.01-1.17, P = 0.02). Postoperative IMRT-SIB associated with a significantly lower risk of any recurrence (HR 0.34, CI 0.18-0.64, P = 0.001) and higher local control (HR 0.06, CI 0.01-0.24, P < 0.01). Additionally, it associated with a lower risk of mucositis (P = 0.029) compared with definitive radio (chemo) therapy. CONCLUSIONS: IMRT-SIB is a safe and feasible radiation treatment technique for pharyngo-laryngeal SCC patients with a tolerable acute toxicity profile.

Concurrent chemoradiotherapy with weekly nedaplatin versus radiotherapy alone in elderly patients with non-small-cell lung cancer.

PURPOSE: We conduct this study to compare the efficacy and toxicity of intensity-modulated radiotherapy (IMRT) concurrent weekly nedaplatin (NDP) versus IMRT alone in the stage III/IV non-surgical elderly patients with non-small-cell lung cancer (NSCLC). METHODS: 117 patients were enrolled into our study. The patients were assigned into two different groups: radiotherapy (RT) group and chemoradiotherapy (CRT) group. Patients in RT group were treated with IMRT at a single daily dose of 2 Gy for 5 days per week, totally 52-66 Gy. The CRT group, IMRT concurrent weekly NDP at a dose of 25 mg/m2. RESULTS: In CRT group, the median survival was 11.0 months (95% confidence interval [CI], 8.894-13.106 months) and in RT group, it was 7.0 months (95% CI 5.771-8.229 months). The 1-year, 2-year, 3-year, survival rates in the combined treatment arm were higher than the radiation therapy arm (46.8 vs 25.9%, 25.1 vs 11.8%, 14.7 vs 8.0%; p < 0.001). The Cox's multiple regression analysis showed that CRT had significantly better overall survival than RT (HR 0.523; 95.0% CI 0.338-0.807; p = 0.003). The objective response rate provided that 73.3% treated with CRT compared with 51.1% (p = 0.018) received RT alone. Of the hematologic toxicities, leukocytes (35.0 vs 0%; p < 0.001), neutrophils (33.3 vs 0%; p < 0.001) were significantly more common in the CRT group than the RT group. CONCLUSIONS: We first discovered that NDP concurrent IMRT for treating stage III/IV non-surgical elderly patients with NSCLC was good curative effect of better objective response rate and well-tolerated. However, within the low number of patients, only stage IV gained a survival benefit.

Intensity-modulated radiotherapy combined with paclitaxel and platinum treatment regimens in locally advanced esophageal squamous cell carcinoma.

PURPOSE: This study was conducted to investigate the efficacy and toxicity of combination treatment with intensity-modulated radiotherapy (IMRT) and concurrent chemotherapy with paclitaxel plus different platinum agents in locally advanced esophageal squamous cell carcinoma (ESCC). METHODS: This retrospective study enrolled 242 patients treated with paclitaxel (135 mg/m2) plus platinum regimens. According to the different platinum agents used, patients were classified into: cisplatin 80 mg/m2 (CP), nidaplatinum 80 mg/m2 (NP), lobaplatin 35 mg/m2 (LP), and oxaliplatin 135 mg m2 (OP) groups, and survival and toxicity rates between the four groups were compared. The median overall survival (OS) was 31.1 months. RESULTS: No significant differences were observed among the CP, NP, LP, and OP groups with regard to 3-year survival rates (46.2, 56.4, 45.7, and 29.0%, respectively). A stratified analysis indicated that 3-year survival rates were significantly lower in the OP group. Renal toxicities and gastrointestinal reactions were more frequent in the CP group than in the other three groups. Three-year survival rates were similar among patients receiving 2, 3, or ≥4 cycles of chemotherapy (40.1, 49.5, and 50.8%, respectively). Multivariate analysis indicated that tumor volume and maximum diameter of metastatic lymph nodes might be independent prognostic factors. CONCLUSION: Paclitaxel plus nidaplatinum or lobaplatin is recommended in locally advanced ESCC due to their satisfying therapeutic effects and less toxicity. Tumor volume and maximum diameter of metastatic lymph nodes are independent prognostic factors in ESCC patients receiving IMRT and concurrent chemotherapy.

Long-Term Progression of Sensorineural Hearing Loss and Tinnitus after Combined Intensity-Modulated Radiation Therapy and Cisplatin-Based Chemotherapy for Nasopharyngeal Carcinoma: A Case Report.

Sensorineural hearing loss (SNHL) is a common adverse effect for nasopharyngeal carcinoma (NPC) patients treated with chemoradiotherapy. We report a case of 12-year follow-up from a patient with stage IIB NPC, treated in 2004 with intensity-modulated radiotherapy and cisplatin-based chemotherapy. Pure-tone audiograms were conducted before treatment and at two other points in the 12-year period after treatment. Analysis of the patient's audiograms reveals that the development of high-frequency SNHL started after treatment and reached a plateau accompanied by tinnitus approximately 32 months after treatment conclusion. After the plateau, high-frequency SNHL continued to develop slowly in the next 10 years, possibly a long-term effect from radiation-induced microvascular change of the hearing apparatus. The continuous high-frequency hearing decline is associated with increased tinnitus pitch in the patient. With experience learned from this case, we recommend hearing tests at regular intervals for at least 3-5 years for NPC patients treated with chemoradiotherapy. Patients need to be educated about tinnitus and counseling can be offered when they begin to feel inconvenienced by tinnitus. These patients also need to be advised against exposure to noise that can aggravate the already compromised hearing apparatus, leading to further hearing loss and worsening tinnitus. Limiting the peak dose and total cumulative dose of cisplatin should be considered based on the patients' risk factors to achieve a balance between treatment efficacy and long-term adverse effects.

Outcome and toxicity of intensity modulated radiotherapy with simultaneous integrated boost in locally advanced non-small cell lung cancer patients.

PURPOSE: The aim of this study was to assess the feasibility and treatment outcome of intensity modulated radiation therapy with simultaneous integrated boost (SIB-IMRT) in locally advanced non-small cell lung cancer (NSCLC) patients. MATERIALS AND METHODS: A total of 64 NSCLC patients with stage IIB (3%), IIIA (36%), and IIIB (61%) were treated with concomitant (N = 47; 73%) or sequential (N = 9; 14%) chemotherapy between February 2009 and January 2014. Eight patients (13%) received RT alone. All patients received the same irradiation scheme using IMRT: prophylactic dose for mediastinum was 56 Gy at 1.65 Gy/fraction and SIB to macroscopic disease up to 68 Gy at 2 Gy/fraction. RESULTS: The median follow-up was 16 months (range, 1-70 months). The overall survival rate for all patients was 79% after 1 year and 46% after 2 years. Disease-free survival (DFS) was 81 and 45% after 1 and 2 years, respectively, resulting in a median DFS of 16 months. Multivariate analysis showed a statistically significant association between stage IIIB patients and a higher risk of mortality (HR 2.11; P = 0.019). In addition, T4 stage associated with higher risk of recurrence (HR 2.23; P = 0.024) while concomitant chemoradiation was associated with lower risk of any recurrence (HR 0.34; P = 0.004) No patient experienced grade ≥3 esophagitis and only 6 cases (9%) had grade 3 pneumonitis. Only having a higher lung volume was associated with higher risk of pneumonitis in the multivariate analysis (HR 16.21; P = 0.022). CONCLUSION: This study in advanced NSCLC patients shows that SIB-IMRT is an effective technique with acceptable toxicity, also when combined with chemotherapy.

Effect of adaptive replanning in patients with locally advanced nasopharyngeal carcinoma treated by intensity-modulated radiotherapy: a propensity score matched analysis.

PURPOSE: Limited data have been published regarding the effect of adaptive radiotherapy (ART) on clinical outcome in patients with nasopharyngeal carcinoma (NPC). We compared the long-term outcomes in patients with locally advanced NPC treated by adaptive intensity-modulated radiotherapy (IMRT) replanning versus IMRT. METHODS: 200 NPC patients with stage T3/T4 were included between October 2004 and November 2010. Patients in both treatment groups were matched using propensity score matching method at the ratio of 1:1. Clinical outcomes were analyzed with Kaplan-Meier method, log-rank test and Cox regression. RESULTS: After matching, 132 patients (66 patients in each group) were included for analysis. The median follow-up for the IMRT replanning group was 70 months, while the IMRT group was 69 months. The 5-year local-regional recurrence-free survival (LRFS) rate was higher in IMRT replanning group (96.7 vs. 88.1 %, P = 0.022). No significant differences in distant metastasis-free survival (DMFS), progression-free survival (PFS) and overall survival (OS) were observed between the two groups. 21.2 % patients in IMRT replanning group and 28.8 % patients in IMRT group had distant metastasis. In multivariable analysis, IMRT replanning was identified as an independent prognostic factor for LRFS (hazard ratio 0.229; 95 % CI 0.062-0.854; P = 0.028), but not for DMFS, PFS and OS. CONCLUSIONS: IMRT replanning provides an improved LRFS for stage T3/T4 NPC patients compared with IMRT. Distant metastasis remains the main pattern of treatment failure. No significant advantage was observed in DMFS, PFS and OS when adaptive replanning was used.

Calidad de vida a largo plazo en una cohorte de adultos mayores chilenos, tratados de cáncer de próstata con radioterapia de intensidad modulada (IMRT) / Long-term quality of life in a cohort of Chilean older adults, treated for Prostate cancer with modulated intensity radiotherapy (IMRT)

Introducción: El cáncer de próstata (CP) presenta una alta prevalencia. La radioterapia con intensidad modulada (IMRT) esuna nueva técnica con impacto poco conocido en la calidad de vida a largo plazo (CDVALP) de estos pacientes. El objetivo fue evaluar CDVALP en este grupo. Materiales y Método: Se incluyeron pacientes tratados entre 2000-2010, con más de 1 año de seguimiento. Se utilizó cuestionario EPIC, que fue completado directamente por el paciente. Se evaluaron dominios objetivos y subjetivos de hábitos urinarios, intestinales, hormonales y sexuales. Estudio aprobado por el comité de ética. Resultados: Se analizaron 45 encuestas. La mediana de edad fue 75 años (rango 55-90), seguimiento 4,4 años (rango 1,5-8,5). Tasa respuesta promedio fue de 96,9 por ciento. La toxicidad moderada-importante objetiva para dominio urinario fue: escape urinario 8,8 por ciento, disuria 4,4 por ciento, incontinencia 4,4 por ciento, uso pañales 2,2 por ciento, hematuria 6,6por ciento. En lo subjetivo, la polaquiuria fue "un problema grande" en 6,7 por ciento. La toxicidad intestinal objetiva moderada-importante fue: frecuencia deposición 8,9 por ciento, diarrea 4,4 por ciento, pujo 6,6 por ciento, incontinencia 4,4 por ciento, hematoquezia 0 por ciento. En el dominio hormonal: bochornos significativos 11,1 por ciento. En dominio sexual: compromiso importante del deseo 57,6 por ciento, erección 66,7 por ciento, orgasmo 55,6 por ciento, en globo 62,4 por ciento, Subjetivamente la disfunción eréctil se consideró "un problema grande" en 31,1 por ciento . En globo, la disfunción sexual subjetiva se consideró importante en 24,4 por ciento y moderada en 17,8 por ciento. Conclusiones: La radioterapia con IMRT se asocia a buena CDVALP en dominios urinario, intestinal, hormonal. La alta toxicidad sexual podría estar asociada a la edad avanzada de los pacientes tratados con radioterapia.(AU)

Background: Prostate cancer has a high prevalence. Intensity modulated radiation therapy (IMRT) is a new technique with little known impact on quality of life (QOL) in the long term of these patients. The objective was to evaluate QOL in this group. Materials and Methods: We included patients from 2000 to 2010, with more than 1 year follow-up. EPIC questionnaire was completed by the patient directly. We evaluated objective and subjective domains urinary and bowel habits, hormonal and sexual symptoms. Study approved by the ethics committee. Results: 45 surveys were analyzed. The median age was 75 years (range 55-90); follow up was 4.4 years (range 1.5-8.5). Average response rate was 96.9 percent. Toxicity moderately important objective for urinary domain was: urinary escape 8,8 percent, dysuria 4,4 percent, incontinence 4.4 percent, use diapers 2,2, hematuria 6,6 percent. In the subjective, polakiuria was "a big problem" in 6,7 percent. Objective Intestinal toxicity moderately important was: deposition rate 8,9. percent, diarrhea 4.4 percent, incontinence 4.4 percent, hematochezia 0 percent. In the hormonal domain clinical significant hot flashes in was 11.1 percent. In sexual domain: significant desire dysfunction in 57.6 percent, erection 66.7, orgasm 55.6 percent, Sexual overall 62.4 percent, subjectively erectile dysfunction was considered "a big problem" in 31.1 percent. Overall, subjective sexual dysfunction was considered important by 24.4 percent and moderate in 17.8 percent. Conclusions: IMRT radiation therapy is associated with good CDVALP in domains urinary, bowel, hormonal. The sexual high toxicity may be associated with older age of patients treated with radiotherapy.(AU)

IMRT delivers lower radiation doses to dental structures than 3DRT in head and neck cancer patients.

BACKGROUND: Radiotherapy (RT) is frequently used in the treatment of head and neck cancer, but different side-effects are frequently reported, including a higher frequency of radiation-related caries, what may be consequence of direct radiation to dental tissue. The intensity-modulated radiotherapy (IMRT) was developed to improve tumor control and decrease patient's morbidity by delivering radiation beams only to tumor shapes and sparing normal tissue. However, teeth are usually not included in IMRT plannings and the real efficacy of IMRT in the dental context has not been addressed. Therefore, the aim of this study is to assess whether IMRT delivers lower radiation doses to dental structures than conformal 3D radiotherapy (3DRT). MATERIAL AND METHODS: Radiation dose delivery to dental structures of 80 patients treated for head and neck cancers (oral cavity, tongue, nasopharynx and oropharynx) with IMRT (40 patients) and 3DRT (40 patients) were assessed by individually contouring tooth crowns on patients' treatment plans. Clinicopathological data were retrieved from patients' medical files. RESULTS: The average dose of radiation to teeth delivered by IMRT was significantly lower than with 3DRT (p = 0.007); however, only patients affected by nasopharynx and oral cavity cancers demonstrated significantly lower doses with IMRT (p = 0.012 and p = 0.011, respectively). Molars received more radiation with both 3DRT and IMRT, but the latter delivered significantly lower radiation in this group of teeth (p < 0.001), whereas no significant difference was found for the other dental groups. Maxillary teeth received lower doses than mandibular teeth, but only IMRT delivered significantly lower doses (p = 0.011 and p = 0.003). Ipsilateral teeth received higher doses than contralateral teeth with both techniques and IMRT delivered significantly lower radiation than 3DRT for contralateral dental structures (p < 0.001). CONCLUSION: IMRT delivered lower radiation doses to teeth than 3DRT, but only for some groups of patients and teeth, suggesting that this decrease was more likely due to the protection of other high risk organs, and was not enough to remove teeth from the zone of high risk for radiogenic disturbance (>30Gy).

Intensity-modulated radiotherapy reduces toxicity with similar biochemical control compared with 3-dimensional conformal radiotherapy for prostate cancer: A randomized clinical trial.

BACKGROUND: The objective of this article was to report the results from a randomized clinical trial comparing intensity-modulated radiotherapy (IMRT) with 3-dimensonal conformal radiotherapy (3DCRT) for the treatment of prostate cancer on a hypofractionated schedule. METHODS: The authors randomly assigned 215 men who had localized prostate cancer to receive hypofractionated radiotherapy to a total dose of 70 grays (Gy) in 25 fractions (at 2.8 Gy per fraction) using either IMRT or 3DCRT. Acute and late gastrointestinal (GI) and genitourinary (GU) toxicity were prospectively evaluated according to modified Radiation Therapy Oncology Group criteria. Biochemical control was defined according to the Phoenix criteria (prostate-specific antigen nadir + 2 ng/mL). RESULTS: In total, 215 patients were enrolled in the IMRT group (n = 109) or the 3DCRT group (n = 106). The 3DCRT arm had a 27% rate of grade ≥ 2 acute GU toxicity compared with a 9% rate in the IMRT arm (P = .001) and a 24% rate of grade ≥ 2 acute GI toxicity compared with a 7% rate in the IMRT arm (P = .001). The maximal rate of grade ≥2 late GU toxicity during the entire period of follow-up was 3.7% in the IMRT group versus 12.3% in the 3DCRT group (P = .02). The maximal rate of grade ≥2 late GI toxicity during the entire follow-up was 6.4% in the IMRT group versus 21.7% in the 3DCRT group (P = .001). The 5-year rate of freedom from biochemical failure was 95.4% in the IMRT arm and 94.3% in the 3DCRT arm (P = .678). CONCLUSIONS: IMRT reduced the delivery of significant radiation doses to the bladder and rectum using a similar target volume. This dosimetric advantage resulted in a lower rate of acute/late grade ≥ 2 GI and GU toxicity for IMRT compared with 3DCRT. Cancer 2016;122:2004-11. © 2016 American Cancer Society.

Stereotactic body radiation therapy and intensity modulated radiation therapy induce different plasmatic cytokine changes in non-small cell lung cancer patients: a pilot study.

PURPOSE: To assess kinetics of plasmatic cytokines during radiation therapy (RT) for locally advanced and early-stage non-small cell lung cancer (NSCLC). METHODS: This prospective study was conducted on 15 early-stage NSCLC underwent to extreme hypofractionated regimen (52 Gy in 8 fractions) with stereotactic body RT (SBRT), and 13 locally advanced NSCLC underwent to radical moderated hypofractionated regimen (60 Gy in 25 fractions) with intensity modulated RT (IMRT). For patients undergoing SBRT, peripheral blood samples were collected on the first day of SBRT (TFd), the last day (TLd) and 45 days (T45d) after the end of SBRT. For patients undergoing IMRT, blood samples were collected at: TFd, 2 weeks (T2w), 4 weeks (T4w), TLd, and T45d. The following cytokines were measured: IL-1, IL-1ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, IL-13, IL-15, IL-17A, EGF, FGF-2, INF-γ, MIP-1α, MIP-1ß, TGF-α, TNF-α, and VEGF. Cytokine levels measured in different RT time and compared. RESULTS: No difference in baseline levels of cytokines was documented between patient radiation approaches (except for MIP-1α). For SBRT patients, a mean reduction of IL-10 and IL-17 plasma level was documented between TLd and TFd, respectively (p < 0.05). For IMRT patients, a statistically significant (p < 0.05) mean plasma level reduction was documented between T4w and TFd for all the following cytokines: IL-1, IL-1ra, IL-2, IL-12, FGF-2, MIP-1α, MIP-1ß, TGF-α, TNF-α, VEGF. CONCLUSIONS: SBRT and IMRT induce different plasmatic cytokine changes in NSCLC patients, supporting hypothesis that RT regimes of dose schedules and techniques have different impacts on the host immune response.

IMRT, RapidArc® and conformal radiotherapy in the treatment of tumours of the anal canal.

PURPOSE: To compare dosimetric results of the use of RapidArc® with simultaneous integrated boost, sliding window intensity-modulated radiotherapy (IMRT) with simultaneous integrated boost, and conformal radiotherapy with sequential boost in the management of anal canal cancer. METHODS: Two patients with squamous cell cancer of the anal canal with compromised inguinal nodes were included. The simulation was performed in the supine position with a customized Vac-Lok™ immobilizer. Treatment volumes and organs at risk were defined in accordance with international recommendations. Dosimetric comparisons were made in the target volume by means of tumour conformity, coverage, and homogeneity indexes; in healthy organs, integral doses were compared. RESULTS: A similar planning target volume coverage was achieved with the three techniques. The two IMRT techniques demonstrated benefits in doses received by healthy organs compared to the conformal radiotherapy. RapidArc® showed reduction in the execution time and monitor units required for treatment compared with sliding window IMRT. CONCLUSIONS: The IMRT showed coverage and tumour conformity indexes similar to those of conformal radiotherapy with better dosimetric results in the organs at risk, which should translate into a better toxicity profile. RapidArc® demonstrated benefits over the sliding window IMRT, which makes treatment more comfortable for the patient with less uncertainty about intrafraction motion and a reduced potential for radiation-induced tumours.