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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.

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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].

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PURPOSE: Analyse the impact of different prognostic factors on G2-late vaginal complications after vaginal brachytherapy (VBT) ± external beam radiotherapy (EBRT) in postoperative endometrial cancer (PEC). METHODS: One hundred and twenty-six PEC patients treated with VBT ± EBRT were retrospectively analysed considering age, body mass index, applicator diameter, clinical target volume (CTV), use of dilators, chemotherapy and EQD2(α/ß=3) at the most exposed 2 cm3 of the CTV as prognostic factors for vaginal complications. Late vaginal complications were evaluated using objective LENT-SOMA criteria. STATISTICS: descriptive analysis, Chi-square, Fisher and Student tests were applied. Univariate and multivariate analyses were performed with the Baptista-Pike exact method and multiple logistic regression. RESULTS: Mean age was 65 years (SD ± 10), and median follow-up was 66 months (8-104). 19/126 patients (15%) showed G2-late vaginal complications, and 107/126 (85%) G0-G1. Univariate analysis showed: CTV ≤ 9 cm3 (p = 0.036), use of dilators < 9 months (p = 0.015), and total ≥ 68 Gy EQD2 received by 2 cm3 of CTV (p = 0.039) were associated with G2-late vaginal toxicity. Multivariate analysis showed the use of dilators < 9 months as an independent prognostic factor for G2-late vaginal toxicity (p = 0.043, OR 8.59, CI 1.59-159.9). CONCLUSION: The use of dilators < 9 months in VBT ± EBRT for PEC was an independent prognostic factor for G2-late vaginal toxicity. The use of vaginal dilators ≥ 9 months requires further analysis in studies evaluating late vaginal toxicity.

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BACKGROUND/PURPOSE: To evaluate the impact of intensity-modulated radiotherapy (IMRT) with intra-prostate fiducial markers image-guided radiotherapy (IGRT) on the incidence of late urinary toxicity compared to 3D conformal radiotherapy (3DCRT) for patients with prostate cancer (PC). METHODS AND MATERIALS: We selected 733 consecutive patients with localized PC treated with dose-escalation radiotherapy between 2001 and 2014. Eligibility criteria were radiation dose >72.0 Gy, no pelvic RT and minimum follow-up 24 months. 438 patients were treated with 3DCRT and 295 with IMRT. Acute and late urinary complications were assessed using the EORTC/RTOG and CTCAEs v3.0 definition. The Cox regression model was used to compare grade ≥2 urinary toxicity between both techniques. The median follow-up was 75 months (range 24-204). RESULTS: The median isocenter radiation dose was 78.7 Gy for 3DCRT and 80.7 Gy for IMRT/IGRT (p < 0.001). The 5-year incidence of late grade ≥2 urinary toxicity was 6.4% for IMRT and 10.8% for 3DCRT [hazard ratio (HR) 0.575, p = 0.056]. The corresponding 5-year estimates of late grade ≥2 hematuria were 2% for IMRT and 5.3% for 3DCRT (HR 0.296, p = 0.024). On multivariate analysis, the antecedent of prior transurethral resection of the prostate was also a strong predictor of a higher risk of urinary complications (HR 2.464, p = 0.002) and of hematuria (HR 5.196, p < 0.001). CONCLUSION: Compared with 3DCRT, high-dose IMRT/IGRT is associated with a lower rate of late urinary complications in spite of higher radiation dose.

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AIM: To report the treatment results of a retrospective cohort of prostate cancer patients treated with Hypo-RT with a high equivalent biological effective dose (BED). BACKGROUND: Hypofractionated radiotherapy (Hypo-RT) has gained popularity and interest in the treatment of prostate cancer. However, there are few experiences with adequate follow-up reporting treatment results using high equivalent dose with Hypo-RT. MATERIALS AND METHODS: We assigned 149 men with low-, intermediate- and high-risk prostate cancer to receive Hypo-RT with a total dose of 69 Gy/23 fractions. Late gastrointestinal (GI) and genitourinary (GU) toxicity were prospectively evaluated according to modified RTOG criteria. Biochemical no evidence of disease (bNED) was defined as the nadir prostate-specific antigen level plus 2 ng/mL. RESULTS: The median follow-up was 53 months. For the entire cohort, the 5-year bNED rate was 94.6%, and for low-, intermediate- and high-risk patients the 5-year bNED was 100%, 96.4%, and 86% (p = 0.007), respectively. The 5-year overall survival rate was 92%. Only 1 patient died from the disease at 48 months after treatment, giving a 5-year cancer-specific survival of 98%. The worst grade ≥2 rate GI and GU toxicity was 13.4% and 14%, respectively. No grade >3 toxicity was observed. The presence of grade ≥2 GI and GU toxicity at the last follow-up was only 1.3% and 3%, respectively. CONCLUSIONS: Hypo-RT (69 Gy/23 fractions) with a high equivalent BED produces excellent rates of biochemical control for low, intermediate and high-risk prostate cancer. The long term GU and GI toxicity rates were considered low and acceptable.

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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.

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Background: VBM chemotherapy (vinblastine, bleomycin and methotrexate) plus irradiation is an effective therapeutic combination in early-stage Hodgkin's lymphoma, but conflicting results have been collected on the toxicity of and correct indication for this combination. Patients and methods: The GISL treated 169 evaluable patients with early-stage, favorable presentation Hodgkin's disease in two successive trials. In the first (MH-1), conducted between 1988-1995, 87 patients were administered the original VBM schedule coupled with extended-field radiotherapy (EF-RT). In the subsequent study (MH1b), performed between 1996-2004, the doses of vinblastine and methotrexate were intensified, the dose of bleomycin was reduced, and small amounts of prednisone were given contemporaneously with any infusion of antitumoral drug (VbMp); irradiation was delivered to involved sites only and had to begin at least 25 days after the end of chemotherapy. Of the 82 patients treated with the MH-1b protocol, 67 were < 65 years old (MH-1b ≤ 65) and 15 were > 65 years old (MH-1b > 65). Results: Complete remission was achieved by 96, 91 and 80% of the patients in the MH-1, MH-1b ≤ 65 and MH-1b > 65 trials, respectively; relapse rates were 12, 9 and 0%, with median follow-ups of 111, 55 and 49 months. Hematological and pulmonary toxicity were acceptable on the whole in the MH-1 group, but more severe when chemotherapy followed radiotherapy than vice versa. In the MH-1b ≤ 65 both these toxicities were abated, while in the MH-1b > 65 severe infections affected 3/15 patients. Conclusions: VbMp followed by involvedfield radiotherapy shows negligible hematological and pulmonary toxicity. The modified protocol appeared as effective as the original VBM + EF-RT protocol, with minimal and not statistically significant differences. The addition of cyclophosphamide to VbMp is under investigation to improve the cell-killing potential of the regimen. The purpose is to cure even early unfavorable presentations of the disease maintaining radiotherapy to involved sites only and avoiding the risk of late cardiotoxicity given by combinations including anthracyclines

Antecedentes: La quimioterapia con vinblastina, bleomicina y metotrexato (VBM) asociada a la irradiación constituye una combinación terapéutica efectiva en el estadio temprano del linfoma de Hodgkin, aunque se publicaron resultados contradictorios respecto de la toxicidad y la indicación adecuada de esta asociación. Pacientes y métodos: El GISL trató y evaluó ­en dos ensayos clínicos­ 169 pacientes en fases tempranas de la enfermedad de Hodgkin con presentación favorable. En el primer estudio (MH-1), realizado entre 1998 y 1995, 87 pacientes fueron medicados con el esquema VBM original asociado a radioterapia de campo extendido (RCE). En el ensayo siguiente (MH-1b), llevado a cabo entre 1996 y 2004, se incrementaron las do-sis de vinblastina y metotrexato, se redujeron las de bleomicina y se administró una pequeña cantidad de prednisona junto con la infusión de cualquier droga antitumoral (VbMp); la irradiación se limitó solamente a los sitios afectados y debía comenzar al menos 25 días después de la finalización de la quimioterapia. De los 82 pacientes tratados con el protocolo MH-1b, 67 tenían 65 años o menos (MH-1b ≤ 65) y 15 eran mayores (MH-1b > 65). Resultados: La remisión completa fue obtenida por 96%, 91% y 80% de los pacientes de los estudios MH-1, MH-1b ≤ 65 y MH1b > 65, respectivamente; las tasas de recaída fueron del 12%, 9% y 0 y las medianas de los períodos de seguimiento de 111, 55 y 49 meses. Para la totalidad del grupo MH-1, la toxicidad pulmonar fue aceptable y más grave cuando la quimioterapia siguió a la radioterapia y no a la inversa. En el grupo M-1b ≤ 65, estas toxicidades fueron mitigadas y en el MH-1b > 65, 3 de 15 pacientes fueron afectados por infecciones graves. Conclusiones: La VbMp seguida de radioterapia del sitio afectado (RSA) presenta una toxicidad hematológica y pulmonar casi nula. El protocolo modificado pareció tan efectivo como el original VBM + RCE y las diferencias fueron mínimas y estadísticamente no significativas. En fases de investigación se estudia el agregado de ciclofosfamida al régimen VbMp con el fin de mejorar su poder citodestructor. El objetivo está constituido por la curación, incluso de las formas tempranas y no favorables de la enfermedad, a través de la aplicación de radioterapia exclusivamente a los sitios afectados y evitar el riesgo de cardiotoxicidad tardía que se observa en las asociaciones con antraciclinas

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