Pineal germinoma in a young adult: A case report

Germinoma; Neurosurgery; Pineal glandGerminoma; Neurocirugía; Glándula pinealGerminoma; Neurocirurgia; Glàndula pinealBackground 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

Image-Guided Radiation Therapy for Squamous Cell Cancer of the Head and Neck in a Specialized Peruvian Public Hospital

Head and neck cancer; Image guided radiotherapy; Squamous cell cancerCáncer de cabeza y cuello; Radioterapia guiada por imagen; Cáncer de células escamosasCàncer de cap i coll; Radioteràpia guiada per imatge; Càncer de cèl·lules escamosesSquamous cell cancer of the head and neck (SCCHN) often requires adjuvant radiotherapy. Radiotherapy for SCCHN is a challenge because the head and neck contain several critical organs that should receive minimal doses of radiation. These organs include the eyes, parotid glands, brainstem, spinal cord, mandible, and thyroid gland. Approaches like image-guided radiotherapy (IGRT) combined with volumetric modulated arc therapy hold the promise to focus radiation to the planning target volume and spare nearby structures while observing potential changes to patient anatomy during treatment to determine whether replanning is required. IGRT, however, requires the frequent imaging of patients to update the treatment plan. In this retrospective study, we present our findings of SCCHN patients treated in a public hospital in Peru. The patients reflected overall demographic trends associated with SCCHN. Each patient was imaged using computed tomography once before radiotherapy and once by cone-beam computed tomography (CBCT) during treatment, for a total of two images. Tumor displacement, planning target volume, gross tumor volume, and neck diameter were compared between the two images. Among the measurements, only a small statistically significant increase in gross tumor volume was observed between the images. However, a minority of patients did experience changes to anatomy, which highlights the need for continued research into criteria to determine which patients are likely to benefit from treatment replanning due to intra-treatment anatomical changes. Alternatively, a lack of frequent CBCT imaging before each session, due to high patient flows and limited staff resources, made it difficult to observe transient changes and trends in each patient. We conclude that the treatment and outcome improvements associated with IGRT are likely associated with frequent imaging during radiotherapy and properly selecting which patients will benefit most from this resource-intensive technique

Consensus on management of castration-resistant prostate cancer on behalf of the Urological Tumours Working Group (URONCOR) of the Spanish Society of Radiation Oncology

Càncer de pròstata resistent a la castració; Oncologia de les radiacions; ConsensCáncer de próstata resistente a la castración; Oncología radioterápica; ConsensoCastration-resistant prostate cancer; Radiation oncology; ConsensusBackground: The knowledge in the field of castration-resistant prostate cancer (CRPC) is developing rapidly, with emerging new therapies and advances in imaging. Nonetheless, in multiple areas there is still a lack of or very limited evidence, and clear guidance from clinicians regarding optimal strategy is required. Methods: A modified Delphi method, with 116 relevant questions divided into 7 different CRPC management topics, was used to develop a consensus statement by the URONCOR group. Results: A strong consensus or unanimity was reached on 93% of the proposed questions. The seven topics addressed were: CRPC definition, symptomatic patients, diagnosis of metastasis, CRPC progression, M0 management, M1 management and sequencing therapy, and treatment monitoring. Conclusions: The recommendations based on the radiation oncology experts' opinions are intended to provide cancer specialists with expert guidance and to standardise CRPC patient management in Spain, facilitating decision-making in different clinically relevant issues regarding CRPC patients

Biochemical Recurrence Surrogacy for Clinical Outcomes After Radiotherapy for Adenocarcinoma of the Prostate

Biochemical recurrence; Radiotherapy; Prostate adenocarcinomaRecurrència bioquímica; Radioteràpia; Adenocarcinoma de pròstataRecurrencia bioquímica; Radioterapia; Adenocarcinoma de próstataPURPOSE The surrogacy of biochemical recurrence (BCR) for overall survival (OS) in localized prostate cancer remains controversial. Herein, we evaluate the surrogacy of BCR using different surrogacy analytic methods. MATERIALS AND METHODS Individual patient data from 11 trials evaluating radiotherapy dose escalation, androgen deprivation therapy (ADT) use, and ADT prolongation were obtained. Surrogate candidacy was assessed using the Prentice criteria (including landmark analyses) and the two-stage meta-analytic approach (estimating Kendall's tau and the R2). Biochemical recurrence-free survival (BCRFS, time from random assignment to BCR or any death) and time to BCR (TTBCR, time from random assignment to BCR or cancer-specific deaths censoring for noncancer-related deaths) were assessed. RESULTS Overall, 10,741 patients were included. Dose escalation, addition of short-term ADT, and prolongation of ADT duration significantly improved BCR (hazard ratio [HR], 0.71 [95% CI, 0.63 to 0.79]; HR, 0.53 [95% CI, 0.48 to 0.59]; and HR, 0.54 [95% CI, 0.48 to 0.61], respectively). Adding short-term ADT (HR, 0.91 [95% CI, 0.84 to 0.99]) and prolonging ADT (HR, 0.86 [95% CI, 0.78 to 0.94]) significantly improved OS, whereas dose escalation did not (HR, 0.98 [95% CI, 0.87 to 1.11]). BCR at 48 months was associated with inferior OS in all three groups (HR, 2.46 [95% CI, 2.08 to 2.92]; HR, 1.51 [95% CI, 1.35 to 1.70]; and HR, 2.31 [95% CI, 2.04 to 2.61], respectively). However, after adjusting for BCR at 48 months, there was no significant treatment effect on OS (HR, 1.10 [95% CI, 0.96 to 1.27]; HR, 0.96 [95% CI, 0.87 to 1.06] and 1.00 [95% CI, 0.90 to 1.12], respectively). The patient-level correlation (Kendall's tau) for BCRFS and OS ranged between 0.59 and 0.69, and that for TTBCR and OS ranged between 0.23 and 0.41. The R2 values for trial-level correlation of the treatment effect on BCRFS and TTBCR with that on OS were 0.563 and 0.160, respectively. CONCLUSION BCRFS and TTBCR are prognostic but failed to satisfy all surrogacy criteria. Strength of correlation was greater when noncancer-related deaths were considered events.Supported by Cancer Research UK Radiation Research Centre of Excellence at The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research (grant A28724) (A.C.T.); Cancer Research UK Programme Grant (C33589/A28284)(A.C.T.); NHS funding to the NIHR Biomedical Research Centre at The Royal Marsden and The Institute of Cancer Research (A.C.T.); grant P50CA09213 from the Prostate Cancer National Institutes of Health Specialized Programs of Research Excellence (A.U.K.); grant PC210066 from the Department of Defense (A.U.K.), the Prostate Cancer Foundation, and the American Society for Radiation Oncology (A.U.K.); and funding from the Chapgier, Bershad, De Silva, and McCarrick Families (A.U.K.)

Health-related quality of life in men with localized prostate cancer treated with radiotherapy: validation of an abbreviated version of the Expanded Prostate Cancer Index Composite for Clinical Practice in Spain

Cáncer de próstata; Evaluación de la calidad de vida; RadioterapiaCàncer de pròstata; Avaluació de la qualitat de vida; RadioteràpiaProstate cancer; Quality-of-life assessment; RadiotherapyBackground Health-related quality of life (HRQoL) is greatly affected by prostate cancer (PCa) and associated treatments. This study aimed to measure the impact of radiotherapy on HRQoL and to further validate the Spanish version of the 16-item Expanded Prostate Cancer Index Composite (EPIC-16) in routine clinical practice. Methods An observational, non-interventional, multicenter study was conducted in Spain with localized PCa patients initiating treatment with external beam radiotherapy (EBRT) or brachytherapy (BQT). Changes from baseline in EPIC-16, University of California-Los Angeles Prostate Cancer Index (UCLA-PCI), and patient-perceived health status were longitudinally assessed at end of radiotherapy (V2) and 90 days thereafter (V3). Psychometric evaluations of the Spanish EPIC-16 were conducted. Results Of 516 patients enrolled, 495 were included in the analysis (EBRT, n = 361; BQT, n = 134). At baseline, mean (standard deviation [SD]) EPIC-16 global scores were 11.9 (7.5) and 10.3 (7.7) for EBRT and BQT patients, respectively; scores increased, i.e., HRQoL worsened, from baseline, by mean (SD) of 6.8 (7.6) at V2 and 2.4 (7.4) at V3 for EBRT and 4.2 (7.6) and 3.9 (8.2) for BQT patients. Changes in Spanish EPIC-16 domains correlated well with urinary, bowel, and sexual UCLA-PCI domains. EPIC-16 showed good internal consistency (Cronbach’s alpha = .84), reliability, and construct validity. Conclusion The Spanish EPIC-16 questionnaire demonstrated sensitivity, strong discriminative properties and reliability, and validity for use in clinical practice. EPIC-16 scores worsened after radiotherapy in different HRQoL domains; however, a strong tendency towards recovery was seen at the 3-month follow-up visit.This study was funded by Astellas Pharma Inc

Sequencing of Androgen-Deprivation Therapy of Short Duration With Radiotherapy for Nonmetastatic Prostate Cancer (SANDSTORM): A Pooled Analysis of 12 Randomized Trials

Càncer de pròstata; Teràpia de privació d'andrògensCáncer de próstata; Terapia de privación de andrógenosProstate cancer; Androgen-deprivation therapyPURPOSE The sequencing of androgen-deprivation therapy (ADT) with radiotherapy (RT) may affect outcomes for prostate cancer in an RT-field size-dependent manner. Herein, we investigate the impact of ADT sequencing for men receiving ADT with prostate-only RT (PORT) or whole-pelvis RT (WPRT). MATERIALS AND METHODS Individual patient data from 12 randomized trials that included patients receiving neoadjuvant/concurrent or concurrent/adjuvant short-term ADT (4-6 months) with RT for localized disease were obtained from the Meta-Analysis of Randomized trials in Cancer of the Prostate consortium. Inverse probability of treatment weighting (IPTW) was performed with propensity scores derived from age, initial prostate-specific antigen, Gleason score, T stage, RT dose, and mid-trial enrollment year. Metastasis-free survival (primary end point) and overall survival (OS) were assessed by IPTW-adjusted Cox regression models, analyzed independently for men receiving PORT versus WPRT. IPTW-adjusted Fine and Gray competing risk models were built to evaluate distant metastasis (DM) and prostate cancer–specific mortality. RESULTS Overall, 7,409 patients were included (6,325 neoadjuvant/concurrent and 1,084 concurrent/adjuvant) with a median follow-up of 10.2 years (interquartile range, 7.2-14.9 years). A significant interaction between ADT sequencing and RT field size was observed for all end points (P interaction < .02 for all) except OS. With PORT (n = 4,355), compared with neoadjuvant/concurrent ADT, concurrent/adjuvant ADT was associated with improved metastasis-free survival (10-year benefit 8.0%, hazard ratio [HR], 0.65; 95% CI, 0.54 to 0.79; P < .0001), DM (subdistribution HR, 0.52; 95% CI, 0.33 to 0.82; P = .0046), prostate cancer–specific mortality (subdistribution HR, 0.30; 95% CI, 0.16 to 0.54; P < .0001), and OS (HR, 0.69; 95% CI, 0.57 to 0.83; P = .0001). However, in patients receiving WPRT (n = 3,049), no significant difference in any end point was observed in regard to ADT sequencing except for worse DM (HR, 1.57; 95% CI, 1.20 to 2.05; P = .0009) with concurrent/adjuvant ADT. CONCLUSION ADT sequencing exhibits a significant impact on clinical outcomes with a significant interaction with field size. Concurrent/adjuvant ADT should be the standard of care where short-term ADT is indicated in combination with PORT.Funding support for this study comes from the Prostate Cancer Foundation and ASTRO to AUK. AUK also thanks generous donations from the DeSilva, McCarrick, and Bershad families. A.T. acknowledges support from Cancer Research UK (C33589/A28284 and C7224/A28724) the National Institute for Health Research (NIHR) Cancer Research Network. This project represents independent research supported by the National Institute for Health research (NIHR) Biomedical Research Centre at The Royal Marsden NHS Foundation Trust and the Institute of Cancer Research, London. N.G.Z. is supported by the American Cancer Society – Tri State CEOs Against Cancer Clinician Scientist Development Grant, CSDG‐20‐013‐01‐CCE (2020)

Escalada de dosis de radioterapia en combinación con deprivación androgénica en el tractamiento del cáncer de próstata de riesgo intermedio y alto

En la última década, han surgido dos conceptos para mejorar el control local y los resultados para pacientes con cáncer de próstata localizado, a saber, la escalda de la dosis con nuevas tecnologías de radioterapia y el tratamiento combinado con la deprivación androgénica. Los estudios institucionales y multiinstitucionales de intensificación de la dosis de radioterapia en cáncer de próstata, han demostrado consistentemente una mejora en la supervivencia libre de enfermedad bioquímica y control local a medida que se administra una dosis creciente de radiación (≥75.6 Gy vs. 70.0 Gy). Esta mejora en los resultados se ha evidenciado principalmente en pacientes con cáncer de próstata de riesgo intermedio y alto. En la actualidad, existe una cantidad considerable de datos para respaldar el uso de la escalada de dosis con RT en pacientes seleccionados con cáncer de próstata, particularmente en aquellos con enfermedad de riesgo desfavorable. Debido a que los ensayos aleatorizados que muestran un mejor resultado con la deprivación androgénica (DA) han utilizado niveles de dosis exclusivamente convencionales de 65 a 70 Gy, la pregunta sobre si la DA conduciría a un beneficio similar en pacientes que reciben RT conformada de dosis alta permanece sin respuesta. GICOR-DART 01/05 inció con el apoyo de una beca FIS (04/2506). Es un ensayo aleatorizado y multicéntrico de fase III que evalúa el potencial de dos años de deprivación de andrógenos adyuvante cuando se combina con neoadyuvancia (4 meses) y dosis altas (78 Gy) de radioterapia conformada (3DCRT e IMRT). Se aleatorizaron 355 pacientes con carcinoma de próstata cT1c-T3bN0, (National Comprehensive Cancer Network) de riesgo intermedio y alto. Solo el 14% recibió irradiación ganglionar pélvica. El objetivo principal del estudio era demostrar una mejora en la supervivencia libre de recidiva bioquímica con una supresión androgénica de largo plazo en el contexto de una escalada de dosis de radioterapia. Este objetivo ha sido alcanzado. La probabilidad a los 5 años de la supervivencia libre de enfermedad bioquímica (BDFS) fue estadísticamente significativa mayor, 90%, en el grupo de deprivación de andrógenos de larga duración (LTAD) (IC 95%: 87% -92%) en comparación, 81% en el de corta duración (STAD) (IC del 95%: 78% -85%), p = 0,019. Con una mediana de seguimiento de tan solo 5 años, el uso de DA a largo plazo parece mejorar significativamente la supervivencia global (95% vs 86%, HR 2,48 [IC 95% 1,31-4,68], p = 0,009), así como la supervivencia libre de metástasis y la supervivencia libre de recidiva bioquímica. Con respecto a la toxicidad tardía, DART 01/05 ha demostrado que la LTAD no se asocia con ningún aumento en la toxicidad vesical o intestinal tardía ≥ 2, pero sí a un aumento significativo en los eventos cardiovasculares en el brazo de LTAD (HR ajustado 2,09 [IC del 95%: 1,17 a 3,72], p = 0,012). La tesis contribuye fundamentalmente en dos puntos. El primero es que, demuestra que para tratar un paciente con cáncer de próstata de alto riesgo, se debe hacer un tratamiento combinado con DA de largo plazo en combinación con la radiación con escalada de dosis. Esta combinación tiene un impacto muy importante en el control bioquímico de la enfermedad y en la supervivencia en pacientes con tumores más agresivos. La escalada de dosis no suple el uso de la DA. En segundo lugar, la combinación de tratamientos no aumenta la toxicidad tardía, pero hay evidencia de un aumento en el desarrollo de eventos cardiovasculares, y no de la muerte cardiovascular.Over the last decade two concepts have emerged to improve local control and outcome for patients with localized prostate cancer, namely, dose escalation with new radiation technologies and combined modality treatment with hormonal therapy. Institutional and multi-institutional studies of dose escalation in prostate cancer, have consistently demonstrated an improvement in biochemical disease free survival and local control as an increasing dose of radiation is delivered (≥75.6 Gy vs. 70.0 Gy). This improvement in outcome has been mainly proved for intermediate and high-risk patients. Other of the recent step-up advances for the treatment of prostate cancer is combined modality treatment using androgen deprivation (AD) and RT. At the present time, there is a considerable amount of data to support the use of AD with RT in selected prostate cancer patients, particularly those with locally advanced, unfavourable-risk disease. Because the randomized trials showing improved outcome with AD have used exclusively conventional dose levels of 65 to 70 Gy, the question as to whether AD would lead to similar benefit in patients receiving high-dose conformal RT remains unanswered. GICOR-DART 01/05 was launched with a FIS (04/2506) grant support. It is a phase III randomized and multicentre trial evaluating the potential additional impact effect of two years adjuvant androgen deprivation when combined with neoadjuvant (4 months) and high-dose (78 Gy) conformal radiotherapy (3DCRT and IMRT). It randomized 355 patients with cT1c-T3bN0, National Comprehensive Cancer Network intermediate and high-risk disease. Only 14% received pelvic nodal radiation. The main objective of the study was to demonstrate an improvement in biochemical recurrence-free survival with long-term androgenic suppression in the context of escalating radiotherapy dose. It has been reached. The 5 year probabilista of biochemical disease free survival (BDFS) was statistically significant higher, 90%, in the long term androgen deprivation group (LTAD) (IC 95%: 87% -92%) in comparison with 81% in the short term group (STAD) (IC 95%: 78 % -85%), p=0.019. With a median follow-up of only 5 years we found that the use of long-term ADT seemed to significantly improve overall survival (95% vs. 86%, HR 2.48 [95% CI 1.31-4.68], p=0.009), as well as metastasis free survival and biochemical recurrence-free survival. On subgroup analysis, the overall survival benefit seemed to be demonstrable for the high-risk patients (HR 3.43, p=0.015) but not intermediate-risk (HR 1.67, P=0.381). Regarding late toxicity, DART 01/05 showed that LTAD was not associated with any increase in late grade ≥ 2 bladder or bowel toxicity, but there was a significant increase in cardiovascular events in the LTAD arm (adjusted HR 2.09 [95% CI 1.17-3.72], p=0.012). The thesis contributes fundamentally in two points. The first, it shows that in order to treat a patient with high-risk prostate cancer, a combination therapy with long-term AD should be done in combination with radiation with dose escalation. This combination has a very important impact on the biochemical control of the disease and on survival in patients with more aggressive tumors. Dose escalation does not replace the use of AD. Second, the combination of treatments does not increase late toxicity, but there is evidence of an increase in the development of cardiovascular events, not cardiovascular death

Phase II Study of ENZAlutamide Combined With Hypofractionated Radiation Therapy (ENZART) for Localized Intermediate Risk Prostate Cancer

Enzalutamide monotherapy; Prostate cancer; RadiotherapyMonoterapia con enzalutamida; Cáncer de próstata; RadioterapiaMonoteràpia amb enzalutamida; Càncer de pròstata; RadioteràpiaBackground: Intermediate-risk prostate cancer (PCa) is usually treated by a combination of external beam radiation therapy (EBRT) and a short course of androgen deprivation therapy (ADT). ADT is associated with multiple side effects, including weight gain, loss of libido, and hot flashes. In contrast, anti-androgen monotherapy is generally better tolerated in spite of higher rates of gynecomastia. Objective: This study assessed the effectiveness of enzalutamide monotherapy combined with hypofractionated EBRT (Hypo-EBRT) for treating intermediate risk prostate cancer. Method: This trial was a multicenter, open-label phase II study of 6 months of enzalutamide monotherapy combined with Hypo-EBRT for intermediate-risk prostate cancer. Hypo-EBRT was initiated 8–12 weeks after initiating enzalutamide. The primary endpoint was PSA decline >80% measured at the 25th week of enzalutamide administration. Secondary end-points included assessment of toxicity, changes in anthropomorphic body measurements, sexual hormones, and metabolic changes. Results: Sixty-two patients were included in the study from January 2018 to February 2020. A PSA decline of >80% was observed in all evaluable patients at the end of enzalutamide treatment and 92% achieved PSA values under 0.1 ngr/ml. All patients remain in PSA response (<80% reduction of the initial values) 6 months after the end of enzalutamide treatment. The most frequent adverse events were hypertension, asthenia, and gynecomastia. There were no significant changes in bone density, body mass index (BMI), or patient-reported outcomes (PROs). Conclusion: Enzalutamide monotherapy is very effective along with hEBRT in reducing PSA levels for patients with intermediate-risk prostate cancer. Longer follow-up is needed to confirm the potential use of this combination in future randomized trials.This is an independent academic study (Canarian Foundation of Health Investigations, FUNCANIS) supported by an unrestricted educational grant from Astellas