Association between Intracellular Calcium Signaling and Tumor Recurrence in Human Non-Functioning Pituitary Adenomas.

Clinically non-functioning pituitary adenomas (CNFPAs) are the second most frequent sellar tumor among studies on community-dwelling adults. They are characterized by the absence of hormonal hypersecretion syndrome, and patients present with compressive symptoms, such as a headache and visual field defects. Immunohistochemically, most CNFPAs are of gonadotrope differentiation, with only a few of them being truly null cell adenomas. Although these tumors express receptors for one or more hypothalamic releasing hormones, to what extent this has an impact on the biological and clinical behavior of these neoplasms remains to be defined. In this research, we evaluated the basal and hypothalamic secretagogue-stimulated intracellular calcium mobilization in 13 CNFPAs, trying to correlate this response to the phenotypic features of the patients. Our results indicate that the recurrence of a CNFPA correlates positively with cellular responsiveness, as measured by spontaneous intracellular calcium activity and the ability to respond to multiple hypothalamic secretagogues. We conclude that this finding may be a useful tool for predicting the clinicopathologic behavior of CNFPAs, by testing the variation of cellular responsiveness to hypothalamic secretagogues.

Machine Learning-Based Prediction of Responsiveness to Neoadjuvant Chemoradiotheapy in Locally Advanced Rectal Cancer Patients from Endomicroscopy.

The protocol for treating locally advanced rectal cancer consists of the application of chemoradiotherapy (neoCRT) followed by surgical intervention. One issue for clinical oncologists is predicting the efficacy of neoCRT in order to adjust the dosage and avoid treatment toxicity in cases when surgery should be conducted promptly. Biomarkers may be used for this purpose along with in vivo cell-level images of the colorectal mucosa obtained by probe-based confocal laser endomicroscopy (pCLE) during colonoscopy. The aim of this article is to report our experience with Motiro, a computational framework that we developed for machine learning (ML) based analysis of pCLE videos for predicting neoCRT response in locally advanced rectal cancer patients. pCLE videos were collected from 47 patients who were diagnosed with locally advanced rectal cancer (T3/T4, or N+). The patients received neoCRT. Response to treatment by all patients was assessed by endoscopy along with biopsy and magnetic resonance imaging (MRI). Thirty-seven patients were classified as non-responsive to neoCRT because they presented a visible macroscopic neoplastic lesion, as confirmed by pCLE examination. Ten remaining patients were considered responsive to neoCRT because they presented lesions as a scar or small ulcer with negative biopsy, at post-treatment follow-up. Motiro was used for batch mode analysis of pCLE videos. It automatically characterized the tumoral region and its surroundings. That enabled classifying a patient as responsive or non-responsive to neoCRT based on pre-neoCRT pCLE videos. Motiro classified patients as responsive or non-responsive to neoCRT with an accuracy of ~ 0.62 when using images of the tumor. When using images of regions surrounding the tumor, it reached an accuracy of ~ 0.70. Feature analysis showed that spatial heterogeneity in fluorescence distribution within regions surrounding the tumor was the main contributor to predicting response to neoCRT. We developed a computational framework to predict response to neoCRT by locally advanced rectal cancer patients based on pCLE images acquired pre-neoCRT. We demonstrate that the analysis of the mucosa of the region surrounding the tumor provides stronger predictive power.

Evaluation of secondary malignancies in a large series of mycosis fungoides.

BACKGROUND: An increased risk of Secondary Malignancies (SMs) in Mycosis Fungoides (MF) has been suggested previously. However, the relationship between this risk and the features of MF is not well-known. OBJECTIVE: To investigate the rate and types of SMs in a large cohort of MF patients focusing on the associated features of these patients. METHODS: The demographic features, subtype, and stage of MF, as well as the temporal relationship between the diagnosis of MF and the development of SMs were determined. Major clinical features of MF in this group were compared with MF patients without association of SMs. RESULTS: Among 730 MF patients with a mean follow-up period of 67.9 ± 52.4 months, 56 SMs were identified in a total of 52 (7.1%) patients. While 28.8% of patients were previously diagnosed with other malignancies, then subsequently had a diagnosis of MF, it was vice versa in 53.8% of patients. Most of the SM-associated MF patients had early-stage (80.7%) and classical type of MF (86.5%) without a significant difference from MF patients without association of SMs; 85.5% and 72.5%, respectively. The most commonly identified SMs were hematologic malignancies (64.3%) including lymphomatoid papulosis (n = 22), Hodgkin's lymphoma (n = 4), non-Hodgkin's lymphoma (n = 5), polycythemia vera (n = 2). Other most commonly associated malignancies were breast cancer (n = 4), prostate cancer (n = 3), renal cell carcinoma (n = 2), melanoma (n = 2), and Kaposi's sarcoma (n = 2). STUDY LIMITATIONS: A single tertiary dermatology center study with a retrospective design. CONCLUSION: Apart from the well-known lymphomatoid papulosis association, systemic hematological malignancies were also quite common in the large cohort of MF patients.

The Brazilian National Oral Health Policy and oral cancer mortality trends: An autoregressive integrated moving average (ARIMA) model.

OBJECTIVE: This study analyzes the effect of the Brazilian National Oral Health Policy (NOHP) on oral cancer mortality rates (OCMR). METHOD: This is an ecological study with secondary oral cancer death data, using interrupted time series analysis (ARIMA, Autoregressive Integrated Moving Average). Annual death data were collected from the Mortality Information System (1996-2019). The outcome was the OCMR, standardized by gender and age We considered the NOHP, categorized as "0" (before its implementation), from 1996 to 2004, and "1 to 15", from 2005 to 2019. ARIMA modeling was carried out for temporal analysis, and regression coefficient estimation (RC). RESULTS: The Brazilian NOHP implementation was associated with an increase in OCMR in the North region (CR = 0.16; p = 0.022) and with a decrease in the Southeast region (CR = -0.04; p<0.001), but did not affect the other macro-regions nor Brazil. The forecast models estimated an increase in OCMR for the North, and Northeast, a decrease for the Southeast, and stability for the South and Brazil. CONCLUSION: The Brazilian NOHP is not being effective in reducing the OCMR. The trends behaved differently in the Brazilian territory, highlighting health inequities. We recommend that the NOHP strengthen the oral health care network, incorporating oral cancer as a notifiable disease, adopting strategies for prevention, screening, and providing opportunities for early treatment of the disease.

The First Population-Level Description of Women Diagnosed With Invasive Breast Cancer in Costa Rica From 2008 to 2012: A Cross-Sectional Study.

INTRODUCTION: Breast cancer is the leading cause of cancer-related deaths among women worldwide. In Costa Rica, it ranks first in incidence and fourth in terms of mortality. However, there is a lack of comprehensive information on treatment patterns and outcomes for breast cancer patients in Costa Rica. METHODS: This study utilized data from the National Tumor Registry, which was merged with the Costa Rica Social Security Fund (CCSS) to ensure comprehensive access to clinical information. The study is prospective and focused on patients diagnosed with breast cancer between January 2008 and December 2012. This combined dataset allowed for a more comprehensive analysis of patient characteristics, treatment patterns, and outcomes related to breast cancer in Costa Rica. RESULTS: Among the 4775 patients diagnosed during this period, 3160 met the inclusion criteria for our study. The average age at diagnosis was 59.1 years, with 32.5% of patients being over the age of 65. Most of the patients (55.4%) identified themselves as homemakers, while 46.5% underwent core needle biopsy for diagnosis. Approximately 60% of women were diagnosed with early-stage disease (IA, IIA, and IIB), while 1.7% had metastatic disease, mainly affecting the bone. The mean interval between diagnosis and surgery was 72 days. Most patients (88.7%) received surgery as their initial treatment, and over half (54.4%) received some form of adjuvant therapy. Additionally, 85.6% of patients completed their prescribed treatment. CONCLUSION: This study provides a comprehensive and detailed description of the characteristics and treatment patterns among breast cancer patients in Costa Rica. The findings contribute to our understanding of the disease in this population and can serve as a foundation for further research and improvement in breast cancer management and care.

Spatial distribution of mortality from colorectal cancer in the southern region of Brazil.

Colorectal cancer (CRC) is the leading cause of death due to cancer worldwide. In Brazil, it is the second most frequent cancer in men and women, with a mortality reaching 9.4% of those diagnosed. The aim of this study was to analyze the spatial heterogeneity of CRC deaths among municipalities in south Brazil, from 2015 to 2019, in different age groups (50-59 years, 60-69 years, 70-79 years, and 80 years old or more) and identify the associated variables. Global Spatial Autocorrelation (Moran's I) and Local Spatial Autocorrelation (LISA) analyses were used to evaluate the spatial correlation between municipalities and CRC mortality. Ordinary Least Squares (OLS) and Geographically Weighted Regression (GWR) were applied to evaluate global and local correlations between CRC deaths, sociodemographic, and coverage of health care services. For all age groups, our results found areas with high CRC rates surrounded by areas with similarly high rates mainly in the Rio Grande do Sul state. Even as factors associated with CRC mortality varied according to age group, our results suggested that improved access to specialized health centers, the presence of family health strategy teams, and higher rates of colonoscopies are protective factors against colorectal cancer mortality in southern Brazil.

Lymph node microcalcifications after neoadjuvant chemotherapy: A therapeutic response marker.

Lymph node microcalcifications are rare events, and when they are accompanied by neoplasia, they usually seem to be associated with a metastatic condition. We present a case of a patient with breast cancer and lymph node microcalcifications undergoing neoadjuvant chemotherapy (NCT). A change in the calcification pattern towards becoming coarse was observed. Calcification represented a marker of axillary disease, and it was resected after NCT. This is the first report of a patient with lymph node microcalcification undergoing NCT. We observed a change in the calcification format, which facilitated lymph node sentinel identification. Pathological evaluation indicated metastatic disease.

Stereotactic body radiation therapy in the treatment of cancer patients with oligometastatic disease: a real world study.

PURPOSE: Stereotactic body radiation therapy (SBRT) is a treatment modality with curative intent for oligometastatic cancer patients, commonly defined by a low-burden metastatic disease with 1-5 systemic metastases. Better knowledge of the clinical profile and prognostic factors in oligometastatic cancer patients could help to improve the selection of candidates who may obtain most benefits from SBRT. The objective of this study was to describe the clinical data and outcome in term of overall survival (OS) of patients with oligometastatic disease treated with SBRT over a 6-year period. METHODS: From 2013 to 2018, 284 solid tumor cancer patients with 1-5 oligometastases underwent SBRT at a large university-affiliated oncological center in Barcelona, Spain. Variables related to the patient profile, tumor, oligometastatic disease, and treatment were evaluated. RESULTS: A total of 327 metastatic tumors were treated with SBRT. In 65.5% of cases, metachronous tumors were diagnosed at least 1 year after diagnosis of the primary tumor. The median age of the patients was 73.9 years and 66.5% were males. The median follow-up was 37.5 months. The most common primary tumors were lung and colorectal cancer, with lung and bone as the most commonly treated metastatic sites. Ninety-three percent of patients showed a Karnofsky score (KPS) between 80 and 100. Adenocarcinoma was the most common histological type. The median overall survival was 53.4 months, with 1-, 2- and 5-year survival rates of 90.5%, 73.9% and 43.4%, respectively. Overall survival rates of breast (67.6 months, 95% CI 56.4-78.9), urological (63.3 months, 95% CI 55.8-70.8), and colorectal (50.8 months, 95% CI 44.2-57.4) tumors were higher as compared with other malignancies (20 months, 95% CI 11.2-28.8 months) (p < 0.001). Patients with Karnofsky score (KPS) of 90 and 100 showed a significantly better survival than those with impaired performance status (p = 0.001). CONCLUSION: SBRT appears to be well tolerated and safe approach in oligometastatic patients. Patients with good performance status and with primary breast, urological and colorectal cancer have higher OS compared with other malignancies. More studies are necessary to evaluate the prognostic factors in oligometastatic disease (OMD) in order to select patients who could benefit more from this therapeutic approach.

Predicted cardiac and second cancer risks for patients undergoing VMAT for mediastinal Hodgkin lymphoma.

BACKGROUND AND PURPOSE: To predict treatment-related cardiovascular disease (CVD) and second cancer 30-year absolute mortality risks (AMR30) for patients with mediastinal Hodgkin lymphoma in a large multicentre radiation oncology network in Ireland. MATERIAL AND METHODS: This study includes consecutive patients treated for mediastinal lymphoma using chemotherapy and involved site radiotherapy (RT) 2016-2019. Radiation doses to heart, left ventricle, cardiac valves, lungs, oesophagus, carotid arteries and female breasts were calculated. Individual CVD and second cancer AMR30 were predicted using Irish background population rates and dose-response relationships. RESULTS: Forty-four patients with Hodgkin lymphoma were identified, 23 females, median age 28 years. Ninety-eight percent received anthracycline, 80% received 4-6 cycles ABVD. Volumetric modulated arc therapy (VMAT) ± deep inspiration breath hold (DIBH) was delivered, median total prescribed dose 30 Gy. Average mean heart dose 9.8 Gy (range 0.2-23.8 Gy). Excess treatment-related mean AMR30 from CVD was 2.18% (0.79, 0.90, 0.01, 0.13 and 0.35% for coronary disease, heart failure, valvular disease, stroke and other cardiac diseases), 1.07% due to chemotherapy and a further 1.11% from RT. Excess mean AMR30 for second cancers following RT were: lung cancer 2.20%, breast cancer in females 0.34%, and oesophageal cancer 0.28%. CONCLUSION: For patients with mediastinal lymphoma excess mortality risks from CVD and second cancers remain clinically significant despite contemporary chemotherapy and photon-RT. Efforts to reduce the toxicity of combined modality treatment, for example, using DIBH, reduced margins and advanced RT, e.g. proton beam therapy, should be continued to further reduce potentially fatal treatment effects.

Radiation-Induced Undifferentiated Pleomorphic Sarcoma after Breast Conserving Therapy: Case Report / Sarcoma Pleomórfico de Mama Radioinduzido Pós-Tratamento Conservador de Câncer de Mama Inicial: Relato de Caso / Sarcoma Pleomórfico de Mama Radioinducido tras Tratamiento Conservador de Cáncer de Mama Inicial: Informe de Caso

Introduction: Breast sarcoma is a rare form of malignancy that arises from connective tissue, comprising less than 5% of all sarcomas. Undifferentiated pleomorphic sarcoma (UPS) of the breast is a rare and aggressive subtype of radiation-induced sarcoma that can occur in treated breast cancer patients. The diagnosis is challenging and often missed due to the low incidence, long latency period, unspecific imaging finding, and difficulties in clinical and histological detection. Case report: A 56-year-old woman was diagnosed with early-stage triple-negative breast cancer in 2013 and underwent breast-conserving therapy (BCT). After five years follow-up, she developed mastalgia and breast induration, and after mammography and ultrasound without suspicious lesions, a magnetic resonance imaging (MRI) was performed and showed a highly suggestive malignancy mass measuring 8.0 cm and invading the chest wall. The core biopsy revealed a spindle cells malignant tumor, negative for pan cytokeratin and most of immuno-histochemical markers, suggesting sarcoma, but requiring investigation of surgical specimen to exclude metaplastic carcinoma. She underwent Halsted radical mastectomy, full-thickness left anterior chest wall resection contemplating segments of the 4th and 5th ribs and reconstruction with synthetic mesh. The surgical specimen evidenced a UPS with clear margins. The patient had good postoperative recovery and remains in follow-up with the mastology team. Conclusion: This report shows that radiation-induced sarcomas of the breast can be difficult to diagnose, and how later treatment can demand a major surgery with higher morbidity. Prognosis may improve if detected early

Introdução: O sarcoma de mama é uma forma rara de câncer que surge do tecido conjuntivo, compreendendo menos de 5% de todos os sarcomas. O sarcoma pleomórfico indiferenciado (SPI) da mama é um subtipo raro e agressivo de sarcoma induzido por radiação que pode surgir em pacientes pós-tratamento conservador de câncer de mama. O diagnóstico é desafiador e, muitas vezes, tardio, em virtude da baixa incidência, longo período de latência, achados de imagem inespecíficos e dificuldades na detecção clínica e histológica. Relato do caso: Paciente do sexo feminino, 56 anos, foi diagnosticada com câncer de mama triplo-negativo estadiamento inicial em 2013 e submetida a tratamento conservador de câncer de mama. Após cinco anos de seguimento, evoluiu com mastalgia e endurecimento mamário e, após mamografia e ultrassonografia sem lesões suspeitas, foi realizada ressonância magnética que evidenciou massa altamente sugestiva de malignidade medindo 8,0 cm com invasão da parede torácica. O resultado da core biopsy revelou um tumor maligno de células fusiformes, negativo para pancitoqueratina e para a maioria dos marcadores imuno-histoquímicos, sugerindo sarcoma, mas exigindo estudo de peça cirúrgica para excluir carcinoma metaplásico. A paciente foi submetida à mastectomia radical de Halsted, ressecção da parede torácica anterior esquerda contemplando segmentos das 4ª e 5ª costelas e reconstrução com tela sintética. O laudo histopatológico da peça cirúrgica evidenciou SPI com margens livres. Evoluiu com boa recuperação pós-operatória, permanecendo em acompanhamento com a equipe de mastologia. Conclusão: O relato de caso ilustra como os sarcomas de mama induzidos por radiação podem ser de difícil diagnóstico e como o tratamento postergado pode exigir uma cirurgia de grande porte com maior morbidade. Estar ciente dessa condição pode melhorar o prognóstico do paciente

Introducción: El sarcoma de mama es una forma rara de cáncer que surge del tejido conectivo y comprende menos del 5% de todos los sarcomas. El sarcoma pleomórfico indiferenciado (SPI) de la mama es un subtipo raro y agresivo de sarcoma inducido por radiación que puede surgir en pacientes después de un tratamiento conservador del cáncer de mama. El diagnóstico es un desafío y, a menudo, se retrasa debido a la baja incidencia, el largo período de latencia, los hallazgos de imagen inespecíficos y las dificultades en la detección clínica e histológica. Informe del caso: Una paciente de 56 años fue diagnosticada de cáncer de mama triple negativo en estadio inicial en 2013 y se sometió a un tratamiento conservador para el cáncer de mama. A los cinco años de seguimiento desarrolló mastalgia y endurecimiento mamario, y tras mamografía y ecografía sin lesiones sospechosas, se realizó una resonancia magnética, que mostró una masa altamente sugestiva de malignidad de 8,0 cm. con invasión de la pared torácica. El estudio anatomopatológico de la lesión mostró un tumor de células fusiformes maligno, negativo para pancitoqueratina y para la mayoría de los marcadores inmuno-histoquímicos, lo que sugería sarcoma, pero requirió un estudio de la pieza quirúrgica para descartar un carcinoma metaplásico. La paciente fue intervenida de mastectomía radical de Halsted, resección de la pared torácica anterior izquierda cubriendo segmentos de las 4ª y 5ª costillas y reconstrucción con malla sintética. El informe histopatológico de la pieza quirúrgica mostró UPS, con márgenes libres. Evolucionó con buena recuperación postoperatoria, permaneciendo en seguimiento con el equipo de mastología. Conclusión: El relato de caso ilustra cómo los sarcomas de mama inducidos por radiación pueden ser difíciles de diagnosticar y cómo el tratamiento tardío puede requerir una cirugía mayor con mayor morbilidad. Ser consciente de esta condición puede mejorar el pronóstico del paciente.Palabras clave: sarcoma; neoplasias de la mama; neoplasias inducidas por radiación; neoplasias primarias secundarias; informes de casos

Optimizing outcomes in secondary AML.

Acute myeloid leukemia (AML) secondary to antecedent hematologic disorder or prior therapeutics for cancer represent a diverse group of leukemias often associated with inferior outcomes. Conventional therapy with cytarabine-based chemotherapy has been the mainstay of care for the past 30 years with disappointing overall outcomes. Novel therapies, including liposomal cytarabine/daunorubicin, and venetoclax-based therapies have emerged as options in recent years based on studies showing improvement in outcomes over standard-of-care therapies. Despite these advances, mutations in TP53 are associated with inferior response to both therapies and represent an area of unmet clinical need. Novel strategies with immune-targeted therapies such as CD47 monoclonal antibodies appear active in early-phase studies, but randomized studies have yet to report outcomes leading to approval. Allogeneic transplant remains the only known curative therapy for many of these cases. Nonetheless, pretransplant high-risk molecular features of secondary AML are associated with inferior outcome despite transplantation. An optimal approach to secondary AML is yet to be determined.

Diagnóstico de cuatro neoplasias primarias sincrónicas en un adulto / Diagnosis of four synchronous primary neoplasms in an adult

Paciente femenina de 72 años. Mediante estudios de imagen (ultrasonido y tomografía), se le identificó lesión en parénquima hepático, anexo derecho, peritoneo y apéndice cecal, y mediante estudio histopatológico se determinó la presencia concomitante de carcinoma hepatocelular de células claras, tumor mucinoso limítrofe de bajo potencial maligno o borderline, pseudomixoma peritoneal y neoplasia mucinosa de bajo grado del apéndice cecal, respectivamente. Debido a que las neoplasias reportadas no guardan relación con el mismo órgano ni con el sistema, se considera que son neoplasias aparecidas al azar y de tipo sincrónico por ser diagnosticadas en el mismo espacio temporal. Se practicó laparotomía exploradora con exéresis de lesión anexial y de apéndice cecal. La lesión hepática recibió quimioembilización transarte rial por radiología intervencionista. Posterior a la intervención quirúrgica, la paciente presenta buen estado general. En seguimiento con resonancia magnética se cataloga con persistencia de lesión hepática ya tratada, por lo tanto, con enfermedad estable; se refiere a oncología clínica para valoración de quimioterapia en el manejo del pseudomixoma peritoneal. Dieciocho meses después de los diagnósticos iniciales, se documenta carcinoma basocelular y se cataloga como neoplasia metacrónica por la diferencia de tiempo entre los diagnósticos

A 72-year-old female patient with a one-year history of abdominal pain in the right upper quadrant, colicky, radiating to the back, accompanied by adynamia and weight loss. Abdominal distension and a painful mass on palpation in the right hypochondrium were evidenced. Imaging studies identified different lesions in the hepatic parenchyma, right adnexa, peritoneum and cecal appendix. The histopathological study described the presence of clear cell hepatocellular carcinoma, borderline mucinous tumor of low malignant potential or borderline, peritoneal pseudomyxoma and low-grade mucinous neoplasm of the cecal appendix respectively, as synchronous neoplasms. An exploratory laparotomy was performed with excision of the adnexal lesion and the cecal appendix. The hepatic lesion received transarterial chemoembilization by interventional radiology. Follow-up with conservative management by clinical oncology was indicated. The patient evolved with good general condition, in the follow-up with magnetic resonance imaging was classified with persistence of stable hepatic lesion. Eighteen months after the diagnosis of synchronous neoplasms, basal cell carcinoma was identified, due to the difference in the time of diagnosis this is considered a metachronous neoplasm

Breast carcinoma metastasis and Wolf's isotopic response.

Wolf's isotopic phenomenon occurs when a new dermatosis appears on a site that has already healed from a previous dermatological disease of another etiology. This report describes the case of a 44-year-old female patient undergoing treatment for breast carcinoma who recently had brownish erythematous lesions appearing on the scar region of previous herpes zoster on the right hemithorax. Histopathology and immunohistochemistry examination confirmed skin metastasis of breast cancer. Herpes zoster scars require attention due to the possibility of an isotopic response as a facilitating factor in some dermatoses, sometimes severe ones, such as neoplasms.

Non-Small-Cell Lung Cancer With CNS Metastasis: Disparities From a Real-World Analysis (GBOT-LACOG 0417).

PURPOSE: Despite the advances in the approach to non-small-cell lung cancer (NSCLC) with CNS metastasis, access to timely diagnosis and treatment may not be optimal in many instances. Our main objective was to describe a cohort of patients with NSCLC with brain metastases from public and private cancer centers, and the differences between patients' presentation, treatment, and outcomes. METHODS: GBOT-LACOG 0417 is a multi-institutional retrospective cohort study of patients diagnosed with NSCLC and CNS metastasis in Brazil. All patients had confirmed diagnosis of NSCLC between January 2010 and December 2015. CNS metastases were identified by imaging. RESULTS: A total of 273 patients were included. Patients treated at public institutions were more often Black or Brown (38.8% v 15.4%), current or former smoker (88.6% v 60.0%), of squamous cell histology (25.0% v 9.1%), EGFR- and ALK-negative (95.9% v 74.9%), and were less frequently assessed by using brain magnetic resonance imaging (38.8% v 83.6%). At public institutions, patients were more often symptomatic (78.1% v 44.6%) and had worse performance status (Eastern Cooperative Oncology Group 2 or higher 61.5% v 10.3%). CNS metastases were larger (median size 25 v 15 mm) and more often surrounded by edema (67.7% v 55.2%) at public institutions. Patients at public institutions were more frequently treated with whole-brain radiation therapy (72.9% v 45.4%) and less frequently with radiosurgery (6.3% v 24.1%). Among patients from private care, median overall survival was 24.2 months (95% CI, 20.0 to 30.6), significantly higher than in public care (median 12.1 months; 95% CI, 6.7 to 13.6; P < .001). CONCLUSION: Our results demonstrate the discrepancy between public and private health care system in the critical setting of patients with CNS metastasis from NSCLC.

Subsequent malignant neoplasms in the pediatric age in retinoblastoma survivors in Argentina.

BACKGROUND: Retinoblastoma survivors in low- and middle-income countries are exposed to high-intensity treatments that potentially place them at higher risk of early subsequent malignant neoplasms (SMNs). METHODS: We followed 714 (403 [56.4%] nonhereditary and 311 [43.5%] hereditary) retinoblastoma survivors diagnosed from August 1987 to December 2016, up to the age of 16 years. We quantified risk of SMNs with cumulative incidence (CI) and standardized incidence ratios (SIR) analysis. Multivariate regression Cox model was used to determine the association of treatments and risk of SMNs. RESULTS: Median follow-up was of 9 years (range: 0.18-16.9) and 24 survivors (3.36%) developed 25 SMNs (n = 22 hereditary, n = 2 nonhereditary). SMNs included sarcomas (osteosarcomas, Ewing sarcomas, rhabdomyosarcomas; n = 12), leukemias (n = 5), and central nervous system tumors (CNS; n = 3). All cases of acute myeloid leukemia (AML) and most of Ewing sarcomas occurred within 5 years of retinoblastoma diagnosis. The type of SMN was the main indicator of mortality (five of five patients with leukemias, six of 12 with sarcomas, and zero of three with CNS tumors died). Compared to the general population, radiation increased the risk of Ewing sarcoma in hereditary survivors by 700-fold (95% CI = 252-2422.6) and chemotherapy increased the risk of AML by 140-fold (95% CI = 45.3-436). The CI of SMNs for hereditary survivors was 13.7% (95% CI = 8.4-22.1) at 15 years. CONCLUSION: Retinoblastoma survivors from Argentina are at higher risk of developing SMNs early in life compared to the general Argentinean population, especially those treated with radiation plus chemotherapy. AML and Ewing sarcoma presented within 5 years of retinoblastoma diagnosis are associated with chemotherapy and radiation exposure.

SEOM-GEMCAD-TTD clinical guidelines for localized rectal cancer (2021).

The management of localized rectal cancer requires a multidisciplinary approach to optimize outcomes, reduce morbidity and prevent under or overtreatments. While early stages may obtain benefit of local resections without any additional therapies, locally advanced rectal cancer becomes a challenge defining the better sequential strategy of surgery, radiotherapy and chemotherapy. The latest results of international phase III studies have positioned the total neoadjuvant therapy as a potential new standard of care in high risk rectal cancers, however, the best schedule is still not well defined.

SEOM-GEINO clinical guideline of systemic therapy and management of brain central nervous system metastases (2021).

Central nervous system (CNS) dissemination is a severe complication in cancer and a leading cause of cancer-related mortality. Brain metastases (BMs) are the most common types of malignant intracranial tumors and are reported in approximately 25% of patients with metastatic cancers. The recent increase in incidence of BMs is due to several factors including better diagnostic assessments and the development of improved systemic therapies that have lower activity on the CNS. However, newer systemic therapies are being developed that can cross the blood-brain barrier giving us additional tools to treat BMs. The guidelines presented here focus on the efficacy of new targeted systemic therapies and immunotherapies on CNS BMs from breast, melanoma, and lung cancers.

The inverse paradigm and the ancestral cell of IDH-wildtype glioblastoma.

Rethinking IDH-wildtype glioblastoma through its unique features can help researchers find innovative and effective treatments. It is currently emerging that, after decades of therapeutic impasse, some traditional concepts regarding IDH-wildtype glioblastoma need to be supplemented and updated to overcome therapeutic resistance. Indeed, multiple clinical aspects and recent indirect and direct experimental data are providing evidence that the supratentorial brain parenchyma becomes entirely and quiescently micro-infiltrated long before primary tumor bulk growth. Furthermore, they are indicating that the known micro-infiltration that occurs during the IDH-wildtype glioblastoma growth and evolution is not at the origin of distant relapses. It follows that the ubiquitous supratentorial brain parenchyma micro-infiltration as a source for the development of widespread distant recurrences is actually due to the silent stage that precedes tumor growth rather than to the latter. All this implies that, in addition to the heterogeneity of the primary bulk, there is a second crucial cause of therapeutic resistance that has never hitherto been identified and challenged. In this regard, the ancestral founder cancer stem cell (CSC) appears as the key cell that can link the two causes of resistance.