Latin American Consensus on the Treatment of Head and Neck Cancer.

Head and neck squamous cell carcinoma (HNSCC) is well known as a serious health problem worldwide, especially in low-income countries or those with limited resources, such as most countries in Latin America. International guidelines cannot always be applied to a population from a large region with specific conditions. This study established a Latin American guideline for care of patients with head and neck cancer and presented evidence of HNSCC management considering availability and oncologic benefit. A panel composed of 41 head and neck cancer experts systematically worked according to a modified Delphi process on (1) document compilation of evidence-based answers to different questions contextualized by resource availability and oncologic benefit regarding Latin America (region of limited resources and/or without access to all necessary health care system infrastructure), (2) revision of the answers and the classification of levels of evidence and degrees of recommendations of all recommendations, (3) validation of the consensus through two rounds of online surveys, and (4) manuscript composition. The consensus consists of 12 sections: Head and neck cancer staging, Histopathologic evaluation of head and neck cancer, Head and neck surgery-oral cavity, Clinical oncology-oral cavity, Head and neck surgery-oropharynx, Clinical oncology-oropharynx, Head and neck surgery-larynx, Head and neck surgery-larynx/hypopharynx, Clinical oncology-larynx/hypopharynx, Clinical oncology-recurrent and metastatic head and neck cancer, Head and neck surgery-reconstruction and rehabilitation, and Radiation therapy. The present consensus established 48 recommendations on HNSCC patient care considering the availability of resources and focusing on oncologic benefit. These recommendations could also be used to formulate strategies in other regions like Latin America countries.

On the use of radiobiological-based optimization functions in radiotherapy treatment planning for prostate and head and neck cases on Monaco and Eclipse TPS / Sobre el uso de funciones de costo basadas en radiobiología en la planeación de tratamientos de radioterapia para casos de próstata y cabeza y cuello en los TPS Monaco y Eclipse

INTRODUCTION Radiobiological-based optimization functions for radiotherapy treatment planning involve dose-volume effects that could allow greater versatility when shaping dose distributions and DVHs than traditional dose volume (DV) criteria. Two of the most commercially available TPS (Monaco and Eclipse) already offer biological-based optimization functions, but they are not routinely used by most planners in clinical practice. Insight into the benefits of using EUD, TCP/NTCP-based cost functions in Monaco and Eclipse TPS was gained by comparing biological-based optimizations and physical-based optimizations for prostate and head and neck cases. METHODS Three prostate and three H&N cases were retrospectively optimized in Monaco and Eclipse TPS, using radiobiological-based cost functions vs DV-based cost functions. Plan comparison involved ICRU Report 83 parameters D95%, D50%, D2% and TCP for the PTV, and NTCP and RTOG tolerance doses for OARs. RESULTS Although there were differences between Monaco and Eclipse plans due to their dissimilar optimization and dose calculation algorithms as well as optimization functions, both TPS showed that radiobiological-based criteria allow versatile tailoring of the DVH with variation of only one parameter and at most two cost functions, in contrast to the use of three to four DV-based criteria to reach a similar result. CONCLUSION Despite the use of a small sample, optimization of three prostate and three head and neck cases allowed the exploration of optimization possibilities offered by two of the most commercially available TPS on two anatomically dissimilar regions. Radiobiological-based optimization efficiently drives dose distributions and DVH shaping for OARs without sacrifice of PTV coverage. Use of EUD-based cost functions should be encouraged in addition to DV cost functions to obtain the best possible plan in daily clinical practice

INTRODUCCION Las funciones de optimización basadas en radiobiología para la planificación del tratamiento de radioterapia implican efectos dosis volumen que podrían permitir una mayor versatilidad a la hora de dar forma a las distribuciones de dosis y DVH que los tradicionales criterios dosis-volumen (DV). Dos de los TPS más disponibles comercialmente (Mónaco y Eclipse) ya ofrecen productos de funciones de optimización de base biológica, pero la mayoría de los planificadores no las utilizan de forma rutinaria en la práctica clínica. El conocimiento de los beneficios del uso de las funciones de costos basadas en EUD, TCP/NTCP en Mónaco y Eclipse TPS se obtuvo comparando optimizaciones de base biológica y optimizaciones físicas para casos de próstata y cabeza y cuello. MÉTODOS Tres próstatas y tres casos de H&N en Mónaco y Eclipse TPS fueron optimizadas retrospectivamente usando funciones de costos basadas en radiobiología vs funciones de costos basadas en DV. La comparación de planes involucró los parámetros del Informe ICRU 83 D95%, D50%, D2% y TCP para el PTV, y dosis de tolerancia NTCP y RTOG para OAR. Resultados. Aunque hubo diferencias entre los planes Mónaco y Eclipse, debido a sus diferentes algoritmos de optimización y cálculo de dosis, así como funciones de optimización, ambos TPS demostraron que el criterio basado en radiobiología permiten una adaptación versátil del DVH con variación de un solo parámetro y como máximo dos funciones de costos, en contraste con el uso de tres o cuatro criterios basados en DV para alcanzar un resultado similar. CONCLUSIÓN A pesar del uso de una muestra pequeña, la optimización de tres casos de próstata y tres de cabeza y cuello permitió la exploración de las posibilidades de optimización que ofrecen dos de los TPS más disponibles comercialmente en dos regiones anatómicamente diferentes. La optimización basada en radiobiología impulsa de manera eficiente las distribuciones de dosis y la configuración de DVH para OAR sin sacrificar Cobertura de PTV. Se debe fomentar el uso de funciones de costos basadas en EUD además de las funciones de costos DV para obtener el mejor posible plan en la práctica clínica diaria

Targeting Education as a Barrier to Implement Hypofractionation: Results of a Country-Wide Training Program.

Introduction: Access to radiation therapy in low- and middle-income countries (LMICs) could be improved with modern hypofractionated radiation therapy schedules, although their adoption remains limited. We aimed to evaluate perceptions regarding hypofractionation and the effect of a dedicated curriculum in an LMIC. Methods and Materials: We developed a pilot e-learning hypofractionation curriculum focused on breast, prostate, rectal cancer, and high-grade glioma in Colombia. International educators taught 13 weekly, 90-minute sessions. Participants completed pre- and postcurriculum questionnaires regarding hypofractionation attitudes, 1 to 5 Likert-scale self-confidence, and practices for 12 clinical scenarios. Physicians' responses were categorically scored "1" (for hypofractionation or ultrahypofractionation) or "0" (for conventional fractionation). We used the paired t test to measure pre- versus postcurriculum differences in self-confidence and the McNemar test to detect differences in hypofractionation selection. Results: Across 19 cities in Colombia, 147 clinicians enrolled: 61 radiation oncologists, 6 radiation oncology residents, 59 medical physicists, 18 physics residents, and 3 other staff. Among physicians, education was the greatest barrier to select hypofractionation, common in ultrahypofractionation for prostate (77.6%) and breast cancer (74.6%) and less common for moderate hypofractionation of prostate (61.2%) and breast cancer (52.2%). Additional perceived barriers included unfamiliarity with clinic protocols (7%-22%), clinical experience (5%-15%), personal preference (3%-16%), and lack of technology (3%-20%), with variation across different clinical settings. After the curriculum, paired (n = 38) physicians' selection of hypofractionation increased across all disease sites (mean aggregate score 6.2/12 vs 8.2/12, P <.001). Self-confidence among paired clinicians (n = 87) increased for prostate ultrahypofractionation (+0.45), rectal ultrahypofractionation (+0.43), breast hypofractionation (+0.38), and prostate hypofractionation (+0.23) (P ≤ .03). Conclusions: In an LMIC with a bundled payment system, lack of education and training was a perceived barrier for implementation of hypofractionation and ultrahypofractionation. A targeted e-learning hypofractionation curriculum increased participant confidence and selection of hypofractionated schedules.

Inestabilidad microsatelital y cáncer gástrico / Microsatellite instability and gastric cancer

La inestabilidad microsatelital es causada por una alteración de los sistemas de reparación de apareamiento incorrecto, que puede afectar los microsatélites dentro de todo el genoma humano, produciendo errores en su replicación. Los estudios publicados, principalmente en la literatura inglesa, han encontrado que algunos tumores, como los gástricos, pueden expresar inestabilidad microsatelital. En la siguiente revisión de tema, se presenta una descripción de los sistemas de reparación de apareamientos incorrectos y su relación con la presencia de inestabilidad microsatelital en los tumores gástricos, así como su posible utilidad clínica, como factor asociado en la respuesta al tratamiento con inmunoterapia en los pacientes con dicha patología

Microsatellite instability is caused by an alteration of the mismatch repair systems, which can affect microsatellites within the entire human genome, causing errors in their replication. Published studies, mainly in the English literature, have found that some tumors, such as gastric ones, can express microsatellite instability. In this review, a description of the mismatch repair systems and their relationship with the presence of microsatellite instability in gastric tumors is presented, as well as its possible clinical utility, as an associated factor in the response to immunotherapy treatment, in patients with gastric cancer

Acquired Hemophilia Secondary to Soft-tissue Sarcoma: Case Report from a Latin American Hospital and Literature Review.

Acquired hemophilia A is a rare bleeding disorder caused by inhibiting antibodies against factor VIII characterized by the presence of severe bleeding, which in occasions can be lethal. The bleeding manifestations typically have a sudden onset and patients have a negative family and personal histories of bleeding, with a normal prothrombin time (PT) and an extended partial thromboplastin time (PTT). Incidence has been calculated to be between 0.2 and 1.48 cases per million per year. Between 6% and 15% of cases are associated with neoplasms. Here, we present a 52-year-old male with back myxofibrosarcoma who developed acquired hemophilia without response to treatment used and ultimately died. The most common cancers associated with acquired hemophilia are lung and prostate cancer. We found one other case of a patient with Kaposi's sarcoma that was unassociated with HIV infection who presented with severe postoperative bleeding. For bleeding in acquired hemophilia A, the treatments of choice are "bypass" agents, such as recombinant-activated factor VIII (rFVIIa) or activated prothrombin complex concentrate. Any delay in the start of treatment or the usage of insufficient doses is associated with the progression of bleeding symptoms and worsening general condition. In the case of acquired hemophilia secondary to neoplasia, it is recommended that immunosuppressive therapy to eradicate the inhibitors be combined with treatment for the underlying neoplastic disease. In our patient, it was not possible to offer a surgical treatment that enabled the control of the neoplasia, nor he was considered a candidate for chemotherapy or radiotherapy, limiting the treatment to immunosuppressive and "bypass" management.

Stereotactic body radiation therapy (SBRT) for high-risk prostate cancer: Where are we now?

PURPOSE: Stereotactic body radiation therapy (SBRT) is increasingly being used for the management of localized prostate cancer. This trend combined with declining use of brachytherapy (BT) has pushed issues and questions regarding the use of SBRT to the forefront. A systematic literature review was conducted to review the current evidence of biochemical disease-free survival (bDFS) and toxicity of SBRT in high-risk (HR) prostate cancer. METHODS AND MATERIALS: A search was carried out on the PubMed and Embase databases. Studies were included if HR patients were treated using SBRT monotherapy or as a boost and bDFS was reported. Selected high-dose-rate (HDR) BT studies including HR patients from published reviews were selected to compare with SBRT results. Data from recent published phase 3 trials involving HR patients were also compared. RESULTS: Our search yielded 8862 articles. Of these, 20 studies with a median follow-up from 1.6 to 7 years were included in this review. The 5-year bDFS was 81% to 91% in monotherapy studies and 90% to 98% in boost studies. For reference, 19 studies that reported treating HR patients with HDR monotherapy or boost were selected. The 5-year bDFS in HDR monotherapy studies and boost studies was 85% to 93% and 72% to 93%, respectively. The incidence of late grade 3 genitourinary toxicity was 0% to 4.4% and 0% to 2.3% in SBRT monotherapy and SBRT boost studies, respectively. CONCLUSION: The evidence for SBRT in HR patients in this review is based on observational studies with relatively few patients and short follow-up (level III evidence). Based on these data and the principles surrounding treatment, SBRT boost should ideally be validated in clinical trials. SBRT monotherapy should be used cautiously in highly selected HR patients outside of a clinical trial. SUMMARY: Stereotactic body radiation therapy (SBRT) is increasingly being used for the management of clinically localized prostate cancer. This trend, combined with the decline in the use of brachytherapy, has pushed issues and questions regarding the use of SBRT to the forefront. A systematic literature review was conducted to establish the current evidence of biochemical and toxicity outcomes of SBRT in high-risk prostate cancer.

Pediatric Nasopharyngeal Cancer: Case Report and Review of the Literature.

Pediatric nasopharyngeal carcinoma, also referred to as cavum carcinoma, is a rare pediatric disease with an infrequent incidence rate. We present the case of a pediatric patient with nasopharyngeal cancer who received an adult schedule of concomitant chemotherapy and conformal radiotherapy with a brachytherapy boost. Adult protocols with high radiotherapy doses are not commonly used in pediatric patients due to the high comorbidity associated with this practice. In this case, the patient displayed excellent overall survival, a longer disease-free period, and fewer side effects and comorbidities, even in the absence of interferon therapy, which is not easily available in low-income countries. In addition, this case shows that conformal radiotherapy and brachytherapy are options that can be used to escalate the radiotherapy dose and decrease side effects. A 12-year-old female pediatric patient presented to our outpatient clinic with an eight-month history of moderate-to-severe otalgia, intermittent hyaline rhinorrhea, asthenia, adynamia, nasal congestion, epistaxis in the previous months, and local pruritus. Upon physical examination, a 60x60 mm mass was detected at level II of the neck, and a biopsy of the lesion confirmed a histopathological diagnosis of undifferentiated carcinoma compatible with nasopharyngeal carcinoma. The patient was considered to have clinical Stage III cancer, and she received an adult Al-Sarraf protocol with chemoradiotherapy and an intracavitary brachytherapy boost. The patient had a complete response, and she remains without local or distance relapse. Treating pediatric nasopharyngeal carcinoma patients with the Al-Sarraf protocol could be a feasible modality, as observed in this clinical case, despite the elevated cost of using interferon-beta in low-income countries when using more advanced radiotherapy techniques such as conformal radiotherapy and now, modulated intensity radiotherapy. It should be noted that brachytherapy boosts should be used with caution in pediatric patients; the potential side effects should be weighed against improved local control.