P53 and pRB induction improves response to radiation therapy in HPV-positive laryngeal squamous cell carcinoma.

INTRODUCTION: Patients with Human Papillomavirus (HPV+)-associated Laryngeal Squamous Cell Carcinoma (LSCC) exhibit dramatically improved survival relative to those with HPV-Negative (HPV-) tumors. In this study, the authors aimed to investigate the radiosensitivity of all available confirmed HPV+ and HPV-LSCC cells in vitro and in vivo. METHODS: Primary LSCC cells were generated from tumor specimens obtained from patients. Real-time PCR was performed to confirm HPV infection and the expression of HPV-related genes (E6 and E7), p53, and pRB. Clonogenic survival assays, western blotting, and flow cytometry were used to assess radiation sensitivity, apoptosis, and the expression of p53 and pRB. p53 and pRB knockout cells were generated using CRISPR/Cas9 technology. RESULTS: HPV+ LSCC cells displayed enhanced radiation sensitivity compared to HPV- cells. Radiation-induced apoptosis in HPV+ LSCC cells, accompanied by increased levels of p53 and pRB. Knockout of p53 or pRB led to radiation resistance and attenuated radiation-induced apoptosis in HPV+ LSCC cells. In vivo experiments showed similar results, where knockout of p53 or pRB decreased radiosensitivity in tumor-bearing mice. CONCLUSION: The present findings demonstrated that HPV+ LSCC cells displayed obvious inherent radiation sensitivity, corresponding to increased apoptosis following radiation exposure. Mechanism study showed that the expression of p53 and pRB in HPV+ cells are required for radiation sensitivity. These findings highlight a novel mechanism by which p53 and pRB play key roles in the radiation sensitivity of HPV+ LSCC compared to HPV-LSCC.

Real-world evidence for oncological outcomes after radiotherapy or surgery for T1a-T1b glottic squamous cell carcinoma: A population-based cohort study.

BACKGROUND: Compare outcomes after surgery (S) or radiotherapy (RT) for T1a-T1b glottic squamous cell carcinoma (T1GSCC) in a population-based cohort study. METHODS: Patients diagnosed with T1GSCC from 1999 to 2020 were identified from a public database. Clinical, demographic, and social data were extracted. Treatment and patient groups and subgroups were compared with log-rank test, Cox proportional test, and propensity-score matched (PSM). RESULTS: Eight hundred and eighty-eight patients with T1GSCC were included in the study, with a median follow-up of 61 months. The 5- and 10-year overall survival (OS) S versus RT were 76% versus 71% and 60% versus 52% (p = 0.02), respectively. In the subgroup analysis, S was associated with better OS for T1b, male, and public service patients (p < 0.05). In the PSM cohort of S versus RT with 110 patients each, there was no significant difference in the OS, CSS, and LC. CONCLUSIONS: T1GSCC has favorable outcomes with S or RT.

Definitive pelvic radiotherapy for patients with newly diagnosed stage IVB cervical cancer: a systematic review.

OBJECTIVE: The objective of this systematic review was to assess the oncologic outcomes of patients with International Federation of Gynecology and Obstetrics (FIGO) 2018 stage IVB cervical cancer receiving definitive pelvic radiotherapy compared with systemic chemotherapy (with or without palliative pelvic radiotherapy). METHODS: This study was registered in PROSPERO (registration number CRD42022333433). A systematic literature review was conducted following the MOOSE checklist. MEDLINE (through Ovid), Embase, and Cochrane Central Register of Controlled Trials were searched from inception until August 2022. The inclusion criteria were patients with metastatic FIGO 2018 stage IVB cervical cancer, a histologic subtype of squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma that received definitive pelvic radiotherapy (≥45 Gy) as part of management compared with systemic chemotherapy with or without palliative (30 Gy) pelvic radiotherapy. Randomized controlled trials and observational studies with two arms of comparison were considered. RESULTS: The search identified 4653 articles; 26 studies were considered potentially eligible after removing duplicates, and 8 met the selection criteria. In total, 2424 patients were included. There were 1357 and 1067 patients in the definitive radiotherapy and chemotherapy groups, respectively. All included studies were retrospective cohort studies, and two were database population studies. The median overall survival reported in seven studies for the definitive radiotherapy arm versus systemic chemotherapy groups were 63.7 months versus 18.4 months (p<0.01), 14 months versus 16 months (p value not reported), 17.6 months versus 10.6 months (p<0.01), 32 months versus 24 months (p<0.01), 17.3 months versus 10 months (p<0.01), and 41.6 months versus 17.6 months (p<0.01), and not reached versus 19 months (p=0.13) respectively, favoring the groups that received definitive pelvic radiotherapy. The high clinical heterogeneity precluded the performance of meta-analysis, and all studies were at serious risk of bias. CONCLUSIONS: Definitive pelvic radiotherapy as part of treatment in patients with stage IVB cervical cancer may improve oncologic outcomes compared with systemic chemotherapy (with or without palliative radiotherapy); however, this is based on low-quality data. Prospective evaluation would be ideal before the adoption of this intervention in standard clinical practice.

The development of radioresistant oral squamous carcinoma cell lines and identification of radiotherapy-related biomarkers.

BACKGROUND: In the treatment of oral squamous cell carcinoma (OSCC), radiation resistance remains an important obstacle to patient outcomes. Progress in understanding the molecular mechanisms of radioresistance has been limited by research models that do not fully recapitulate the biological features of solid tumors. In this study, we aimed to develop novel in vitro models to investigate the underlying basis of radioresistance in OSCC and to identify novel biomarkers. METHODS: Parental OSCC cells (SCC9 and CAL27) were repeatedly exposed to ionizing radiation to develop isogenic radioresistant cell lines. We characterized the phenotypic differences between the parental and radioresistant cell lines. RNA sequencing was used to identify differentially expressed genes (DEGs), and bioinformatics analysis identified candidate molecules that may be related to OSCC radiotherapy. RESULTS: Two isogenic radioresistant cell lines for OSCC were successfully established. The radioresistant cells displayed a radioresistant phenotype when compared to the parental cells. Two hundred and sixty DEGs were co-expressed in SCC9-RR and CAL27-RR, and thirty-eight DEGs were upregulated or downregulated in both cell lines. The associations between the overall survival (OS) of OSCC patients and the identified genes were analyzed using data from the Cancer Genome Atlas (TCGA) database. A total of six candidate genes (KCNJ2, CLEC18C, P3H3, PIK3R3, SERPINE1, and TMC8) were closely associated with prognosis. CONCLUSION: This study demonstrated the utility of constructing isogenic cell models to investigate the molecular changes associated with radioresistance. Six genes were identified based on the data from the radioresistant cells that may be potential targets in the treatment of OSCC.

Impact of photobiomodulation in a patient-derived xenograft model of oral squamous cell carcinoma.

BACKGROUND: Photobiomodulation therapy (PBMT) is an effective method for the prevention of oral mucositis. However, the effects of PBMT on oral squamous cell carcinoma (OSCC) have not yet been fully elucidated. This study aimed to evaluate the impact of PBMT in an OSCC-patient-derived xenograft (OSCC-PDX) model. METHODS: BALB/c nude mice with OSCC-PDX models were divided into Control, without PBMT (n = 8); Immediate irradiation, PBMT since one week after tumor implantation (n = 6); and Late irradiation, PBMT after tumors reached 200 mm3 (n = 6). OSCC-PDX were daily irradiated (660 nm; 100 mW; 6 J/cm2 ; 0,2 J/point) for 12 weeks. The tumors were collected and submitted to volumetric, histological, immunohistochemistry, and cell cycle analysis. RESULTS: No significant differences in the volumetric measurements (p = 0.89) and in the histopathological grade (p > 0.05) were detected between the groups. The immunohistochemical analysis of Ki-67 (p = 0.9661); H3K9ac (p = 0.3794); and BMI1 (p = 0.5182), and the evaluation of the cell cycle phases (p > 0.05) by flow cytometry also did not demonstrate significant differences between the irradiated and non-irradiated groups. CONCLUSION: In this study, PBMT did not impact the behavior of OSCC-PDX models. This is an important preclinical outcome regarding safety concerns of the use of PBMT in cancer patients.

Laser photobiomodulation does not alter clinical and histological characteristics of 4-NQO-induced oral carcinomas and leukoplakia in mice.

OBJECTIVE: This study evaluated the effect of laser photobiomodulation (PBM) on oral leukoplakia and squamous cell carcinomas (OSCC) in a model of oral carcinogenesis. MATERIALS AND METHODS: Forty-one C57Bl/6 female mice were distributed in control group, 4-NQO group, Laser group 1.5 J and Laser group 9 J. Oral cancer was induced on the tongue by nitroquinoline oxide (4-NQO), diluted in the water for 16 weeks. In the 18th and 19th weeks, PBM with a diode laser, 0.028 cm2 spot size, continuous emission mode, 660 nm wavelength was applied on the tongue of animals for seven sessions. Laser group 1.5 J received 30 mW power and 1.5 J energy. In the Laser group 9 J, 100 mW power, and 9 J energy were applied. In the 20th week the animals were euthanized. RESULTS: All animals exposed to carcinogen developed clinical and histological alterations such as leukoplakia and OSCC on the tongue. There was no significant difference among Laser groups 1.5 and 9 J and 4-NQO group (not irradiated) regarding the area of leukoplakia and carcinomas (P > 0.05) or thickness of epithelial tissue and keratin (P > 0.05). There were also no association between PBM and histologic classification of the lesions (P = 0.87), frequency of OSCC (P = 0.57), grade of tumor differentiation (P = 0.88) or depth of invasion (P = 0.45). CONCLUSION: Laser PBM, in both parameters used, does not influence on clinical and histological characteristics of oral leukoplakia and OSCC. CLINICAL RELEVANCE: Results suggest that PBM may be a safe treatment for adverse effects of antineoplastic therapies in patients with leukoplakia and OSCC.

Effect of low-level light therapy before radiotherapy in oral squamous cell carcinoma: An in vitro study.

Radiation therapy for head and neck squamous cell carcinoma (HNSCC) is associated with several complications. Although photobiomodulation (PBM) has radioprotective effects in normal tissue, it could also enhance the growth of neoplastic cells. Thus, the present study aimed to investigate the cellular response of oral squamous cell carcinoma with pre-exposure to low-level phototherapy before radiotherapy. SCC9, Cal-27, A431, and HaCaT cell lines were subjected to low-level light therapy and radiotherapy. The cells were treated with a single energy density (300 J/cm2) of a light-emitting diode (660 nm) prior to ionizing radiation at different doses (0, 2, 4, and 6 Gy). After 24 h, wound scratch, proliferation, clonogenic cell survival, cell death, and reactive oxygen species (ROS) analyses were performed to evaluate cell response. The cell lines pre-exposed to PBM at the analyzed dosage were radiosensitive. The treatment significantly reduced cell proliferation and clonogenic cell survival. Migration and cell death assays also revealed positive results, with the treatment group showing lower rate of migration and higher cell death than did the control group. Moreover, PBM effectively increased the intracellular levels of ROS. PBM at 300 J/cm2 is a promising radiosensitizing modality to reduce the radiation dose and avoid the intolerable side effects of radiotherapy for HNSCC, thus increasing the probability of successful treatment. However, further studies are needed to support and confirm the results.

Salvage Post-Operative Stereotatic Ablative Radiotherapy for Re-Current Squamous Cell Carcinoma of Head and Neck.

Background and Objectives: Patients with recurrent squamous cell carcinoma of the head and neck (rHNC) face an aggressive disease. Surgical resection is the gold standard treatment. Immediate adjuvant post-operative stereotactic ablative radiotherapy (PO-SABR) for rHNC is debatable. Materials and Methods: We retrospectively identified patients who were treated with PO-SABR at the AC Camargo Cancer Center, Brazil. Results: Eleven patients were treated between 2018 and 2021. The median time between salvage surgery and PO-SABR was 31 days (range, 25-42) and the median PO-SABR total dose was 40 Gy (range, 30-48 Gy). The 2-and 4-year actuarial DFS were 62.3% and 41.6%, while the 2-and 4-year OS probabilities were 80.0% and 53.3%, respectively. Eight (72.7%) patients were alive and six (54.5%) were without disease at the last follow-up. Two (18.1%) patients had local failure in the PO-SABR field. Three (27.3%) patients had distant metastasis, diagnosed in a median time of 9 months (range, 4-13) after completion of PO-SABR. On univariate analysis, predictive factors related to worse OS were: interval between previous radiotherapy and PO-SABR ≤ 24 months (p = 0.033) and location of the salvage target in the oral cavity (p = 0.013). The total dose of PO-SABR given in more than three fractions was marginally statistically significant, favoring the OS (p = 0.051). Conclusions: Our results encourage the use of a more aggressive approach in selected patients with rHNC by combining salvage surgery with immediate PO-SABRT, but this association needs to be further explored.

Comparison of Photon Isoeffective Dose Models Based on In Vitro and In Vivo Radiobiological Experiments for Head and Neck Cancer Treated with BNCT.

Boron neutron capture therapy (BNCT) is a treatment modality for cancer that involves radiations of different qualities. A formalism that proved suitable to compute doses in photon-equivalent units is the photon isoeffective dose model. This study addresses the question whether considering in vitro or in vivo radiobiological studies to determine the parameters involved in photon isoeffective dose calculations affects the consistency of the model predictions. The analysis is focused on head and neck squamous cell carcinomas (HNSCC), a main target that proved to respond to BNCT. The photon isoeffective dose model for HNSCC with parameters from in vitro studies using the primary human cell line UT-SCC-16A was introduced and compared to the one previously reported with parameters from an in vivo oral cancer model in rodents. Both models were first compared in a simple scenario by means of tumor dose and control probability calculations. Then, the clinical impact of the different dose models was assessed from the analysis of a group of squamous cell carcinomas (SCC) patients treated with BNCT. Traditional dose calculations using the relative biological effectiveness factors derived from the SCC cell line were also analyzed. Predictions of tumor control from the evaluated models were compared to the patients' outcome. The quantification of the biological effectiveness of the different radiations revealed that relative biological effectiveness/compound biological effectiveness (RBE/CBE) factors for the SCC cell line are up to 20% higher than those assumed in clinical BNCT, highlighting the importance of using experimental data intimately linked to the tumor type to derive the model's parameters. The comparison of the different models showed that photon isoeffective doses based on in vitro data are generally greater than those from in vivo data (∼8-16% for total tumor absorbed doses of 10-15 Gy). However, the predictive power of the two models was not affected by these differences: both models fulfilled conditions to guarantee a good predictive performance and gave predictions statistically compatible with the clinical outcome. On the other hand, doses computed with the traditional model were substantially larger than those obtained with both photon isoeffective models. Moreover, the traditional model is statistically rejected, which reinforces the assertion that its inconsistencies are intrinsic and not due to the use of RBE/CBE factors obtained for a tumor type different from HN cancer. The results suggest that the nature of the radiobiological data would not affect the consistency of the photon isoeffective dose model in the studied cases of SCC head and neck cancer treated with BPA-based BNCT.

Prognostic factors in locally advanced cervical cancer with pelvic lymph node metastasis.

OBJECTIVE: To evaluate the prognostic impact of clinical and pathological variables and patterns of recurrence in patients with locally advanced cervical cancer with pelvic lymph node involvement (stage IIIC1 according to the 2018 FIGO Staging System). METHODS: We retrospectively analyzed 62 patients with locally advanced cervical cancer treated with curative intent with radiotherapy associated with chemotherapy in AC Camargo Cancer Center from January 2007 to December 2018. RESULTS: Lymph node involvement was assessed by CT, MRI and positron emission tomography (PET)/CT in 28 (45.2%), 20 (32.3%) and 14 (22.6%) patients, respectively. The median tumor size was 5.0 cm and 72.6% of cases were squamous cell carcinomas. The median number of positive pelvic lymph nodes was three, and the median size of lymph nodes was 24 mm. Twenty-two (35.5%) patients had recurrence and 50% had only one site of recurrence. The sites of recurrence were pelvic, para-aortic and distant in 12 (19.4%), 6 (9.7%) and 16 (25.8%) patients, respectively. The 3 year overall and disease-free survival were 70.8% and 64.6%, respectively. Patients with adenocarcinoma had worse disease-free survival (HR 2.38; 95% CI 1.01 to 5.60; p=0.047) and overall survival (HR 2.99; 95% CI 1.14 to 7.75; p=0.025) compared with squamous cell carcinoma. In multivariate analysis, metastatic pelvic lymph node size of >2.5 cm (HR 4.38; 95% CI 1.65 to 11.6; p=0.003) and incomplete response to radiotherapy (HR 5.14; 95% CI 1.60 to 16.4; p=0.006) maintained the negative impact for overall survival. CONCLUSIONS: We found that pelvic lymph node size and incomplete response to radiotherapy negatively impact overall survival in patients with advanced cervical cancer with pelvic lymph node involvement. This finding may help to stratify risk in this group of patients.

Cirurgia Guiada para Instalação de Implantes em Paciente Submetido à Radioterapia em Região de Cabeça e Pescoço / Guided Surgery for Implant Surgery in a Patient Undergoing Radiotherapy in Head and Neck Region / Cirugía Guiada para la Colocación de Implantes en Pacientes Sometidos a Radioterapia en la Región de la Cabeza y el Cuello

Introdução: O uso dos implantes osseointegrados para reabilitação de pacientes com dificuldade de adaptação de próteses convencionais mostra-se mais frequente a cada dia. Um grande grupo candidato à reabilitação com essa modalidade são os pacientes tratados para as neoplasias de cabeça e pescoço (CP). A irradiação na região de CP pode ser limitante para a instalação de implantes, porém a literatura apresenta evidências de técnicas e planejamentos favoráveis ao procedimento nesse grupo de pacientes. As técnicas menos traumáticas para intervenções na cavidade oral devem ser avaliadas, e os guias cirúrgicos para colocação de implantes podem ser aliados nesses procedimentos. Relato do caso: Paciente do sexo feminino, 64 anos, tratada com cirurgia, quimioterapia e radioterapia em cavidade oral para um carcinoma espinocelular (CEC) em língua e, em um segundo momento, diagnosticada e tratada com cirurgia para CEC em região de rebordo alveolar maxilar esquerdo por meio de hemipalatecmia, necessitava de reabilitação com implantes osseointegrados na região onde havia sido tratada com radiação primariamente. Realizou-se a cirurgia de colocação dos implantes com a tecnologia guiada para acarretar o mínimo trauma às estruturas bucais. Conclusão: O procedimento cirúrgico foi executado com sucesso. Atualmente, aguarda-se o período de osseointegração para a posterior reabilitação protética

Introduction: The use of osseointegrated implants for the rehabilitation of patients with difficulty fitting conventional prostheses is becoming more frequent every day. A great eligible group for rehabilitation with this modality are patients treated for head and neck cancer (HNC). Irradiation in the region of HN may be limiting for implants, but there are evidences in the literature of techniques and planning favorable to the procedure in this group of patients. Less traumatic techniques for interventions in the oral cavity should be evaluated, and surgical guides for implant placement may be allies in these procedures. Case report: A 64-year-old female patient, treated with surgery, chemotherapy and radiotherapy in the oral cavity for a squamous cell carcinoma (SCC) in the tongue and, in a second moment, diagnosed and treated with surgery for SCC in the region of the left maxillary alveolar ridge by means of hemipalatectomy, needed rehabilitation with osseointegrated implants in the region where she had been primarily treated with radiation. The implant placement surgery was then planned and performed using guided technology so that minimal trauma to the oral structures could occur. Conclusion: The surgical procedure was successfully performed, and the patient is now waiting for the osseointegration period for posterior prosthetic rehabilitation

Introducción: El uso de implantes osteointegrados para la rehabilitación de pacientes con dificultades de adaptación de las prótesis convencionales es cada vez más frecuente. Un gran grupo de candidatos a la rehabilitación con esta modalidad son los pacientes tratados por neoplasias de cabeza y cuello (CC). La irradiación en la región del CC puede ser limitante para la instalación del implante, sin embargo, la literatura presenta evidencias de técnicas y planificación favorables al procedimiento en este grupo de pacientes. Deben evaluarse técnicas menos traumáticas para las intervenciones en la cavidad oral, y las guías quirúrgicas para la colocación de implantes pueden ser un aliado en estos procedimientos. Caso clínico: Paciente de 64 años, mujer, tratada con cirugía, quimioterapia y radioterapia en la cavidad oral por un carcinoma de células escamosas (CCE) en la lengua y en un segundo momento diagnosticada y tratada con cirugía por CCE en la región de la cresta alveolar maxilar izquierda mediante hemipalatectomía, necesitó rehabilitación con implantes osteointegrados en la región donde había sido tratada principalmente con radiación. La cirugía de colocación de implantes se realizó con tecnología guiada para causar el menor traumatismo en las estructuras orales. Conclusión: La intervención quirúrgica se llevó a cabo con éxito. Actualmente se espera el periodo de osteointegración para la posterior rehabilitación protésica

Epidemiological profile of women with gynecological cancer in brachytherapy: a cross-sectional study.

OBJECTIVE: to analyze the sociodemographic and clinical profile of women with gynecological cancer in brachytherapy. METHOD: a cross-sectional study including records of 1,930 visits of women in brachytherapy assisted between 2006-2016 in Santa Catarina (Brazil). Collection was performed in 2019, in an institutional bank, submitted to frequency measurements, chi-square test, 95% confidence intervals, significance level of 0.05. RESULTS: women aged 40-59 years (47.2%), white (93.3%); with elementary school (65%); cervical cancer (78.5%); stages II-III (73.3%) figured prominently. In the comparison of staging proportions in the topography variable, a higher proportion of malignant neoplasm of cervix uteri unspecified in the grouped III-IV staging (84.6%). CONCLUSION: the profile analysis shows the need for screening and health education for prevention and/or early detection of gynecological cancers and training of nurses specialized in radiotherapy to care for women's health.

Carcinoma Epidermoide de Canal Anal: a propósito de un caso / Squamous Cell Carcinoma of the Anal Canal. About a case

El cáncer de canal anal y ano, es considerado como poco frecuente, sin embargo, ha aumentado ligeramente su incidencia representando del 1 al 2 por ciento de todas las neoplasias del intestino grueso. Dentro de los factores que se asocian a la génesis de estos tumores se encuentra la afección por el virus del papiloma humano. Se presenta el caso de una paciente femenina de 32 años que acude al servicio de Radioterapia del Hospital Clínico Quirúrgico Hermanos Ameijeiras, con antecedentes de Síndrome de Down y diagnóstico de un carcinoma epidermoide del ano y región perianal, variante exofítico y con antecedentes de infección por el virus del papiloma humano. Es evaluada en equipo multidisciplinario y no tiene criterio de cirugía por el tamaño tumoral, por lo que se decidió según estadiamiento la quimioradioterapia concurrente. La paciente presentó una respuesta completa al tratamiento con radioterapia, sin presentar complicaciones, con lo que se demuestra la efectividad de la radioterapia en los tumores del ano y canal anal(AU)

Cancer of the anal canal and anus is considered rare, however, its incidence has slightly increased representing 1 to 2 percent of all neoplasms of the large intestine. Among the factors that are associated with the genesis of these tumors is the condition by the human papillomavirus. We present the case of a 32-year-old female patient who attends the Radiotherapy service of the Hermanos Ameijeiras Clinical Surgical Hospital, with a history of Down Syndrome and a diagnosis of a squamous cell carcinoma of the anus and perianal region, exophytic variant and with a history of infection by the human papillomavirus. It is evaluated in a multidisciplinary team and has no surgical criteria due to tumor size, so it was decided according to staging concurrent chemoradiotherapy. The patient presented a complete response to treatment with radiotherapy, without presenting complications, which demonstrates the effectiveness of radiotherapy in tumors of the anus and anal canal(EU)

Effects of photobiomodulation on cellular viability and cancer stem cell phenotype in oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is the most common head and neck malignancy; it has been shown that cancer stem cells (CSC) are present in OSCC and associated with tumor growth, invasion, metastasis, and therapeutic resistance. Photobiomodulation (PBM) is an alternative tool for oncologic treatment adverse effects such as oral mucositis (OM); however, controversy exists regarding the undesirable effects of PBM on tumor or CSC. This study aimed to evaluate in vitro, the effects of PBM, with the same dosimetric parameters as those used in the clinic for OM prevention and treatment, on OSCC cellular viability, as well as PBM's effect on CSC properties and its phenotype. OSCC cell lines were submitted to single or daily PBM with 3 J/cm2 and 6 J/cm2 and then the cellular viability was evaluated by MTT, NRU (neutral red uptake), and CVS (crystal violet staining). The CSC populations were evaluated by clonogenic formation assay, flow cytometry, and RT-qPCR. The single PBM with the 3 J/cm2 group was associated with increased cellular viability. Daily PBM with 3 J/cm2 and 6 J/cm2 was associated with a significant decrease in cellular viability. Additionally, daily PBM was not able to promote CSC self-renewal or the CD44high/ESAlow and CD44high/ESAhigh cellular phenotypes. Moreover, a decrease in the number of spheres and in the expression of the CSC related gene BMI1 was observed after daily PBM with 6 J/cm2. Daily PBM with 3 J/cm2 and 6 J/cm2 showed an inhibitory effect on cellular viability and was not able to promote the CSC self-renewal or phenotype.

Patterns of oral mucositis in advanced oral squamous cell carcinoma patients managed with prophylactic photobiomodulation therapy-insights for future protocol development.

To characterize oral sites affected by radiation-induced oral mucositis (OM) and related clinical outcomes in oral cancer patients subjected to prophylactic photobiomodulation therapy (PBMT). This study included advanced oral squamous cell carcinoma (OSCC) patients treated with prophylactic PBMT for OM. The site distribution of OM, OM grading (CTCAE NCI, Version 4.0, 2010), OM-related pain (VAS), analgesic protocol (WHO Analgesic Ladder), and use of enteral nutrition were evaluated weekly during treatment. Data analysis was performed using descriptive statistics expressed as median values and percentages. A total of 145 OSCC patients were included. OM most frequently affected the lateral border of the tongue (44.1%), buccal mucosa (37.2%), and labial mucosa (33.8%). Keratinized oral mucosa sites, including the tongue dorsum (6.21%), retromolar trigone (8.3%), and hard palate (2.76%), were less frequently affected. Peak OM scores were observed at weeks 5, 6, and 7, with severe OM (NCI grades 3 and 4) rates of 11%, 20%, and 25%, respectively. The cumulative occurrence of severe OM was 23%, which developed as early as week 3 and as late as week 7. The highest mean value of OM-related pain (2.7) was observed at the sixth week, and 13.8% of the patients required feeding support. This study showed, compared with studies that did not provide PBMT, reduced severity of mucositis, reduced pain and analgesic use, and reduced tube feeding in patients treated with PBMT. OM involving keratinized and non-keratinized surfaces should be included in the prophylactic PBMT to reduce severe OM in future studies.

Metástasis cervical con primario desconocido, cambios en los paradigmas: revisión sobre el enfrentamiento clínico, estudio y tratamiento / Cervical metastases from unknown primary tumor, paradigm changes: review on clinical confrontation, study and treatment

Resumen En adultos, una masa cervical detectada mediante examen físico o un estudio de imagen puede ser la única manifestación de un cáncer proveniente de cabeza y cuello. Un retraso en el diagnóstico repercute en el pronóstico de la enfermedad, por lo que debe haber un alto índice de sospecha. Las metástasis cervicales con primario desconocido (MCCPD) son tumores metastásicos en los que el estudio diagnóstico no logró identificar el sitio primario del cáncer, con una histología predominantemente de tipo escamosa. Según algunos estudios, el origen más frecuente resultó ser la orofaringe, incluyendo amígdala palatina y base de lengua. Factores de riesgo conocidos son edades avanzadas, consumo de tabaco y de alcohol. Actualmente, la infección por el virus del papiloma humano (VPH) está teniendo un rol cada vez más importante como factor de riesgo, formando parte de entre 20%-25% de los cánceres de cabeza y cuello. Al enfrentarse a un paciente con masa cervical es importante realizar una completa anamnesis y examen físico acucioso para detectar cualquier elemento sugerente de malignidad. Se debe complementar con nasofibroscopía para visualizar estructuras que no alcanzan a evaluarse en el examen habitual. También se puede orientar la búsqueda del primario desconocido en base a los patrones de drenaje linfático. Dentro del estudio complementario se puede comenzar con una tomografía computada (TC) y se puede considerar también el ultrasonido o un PET/TC. Si con esto aún no se logra definir el primario, continuar con una punción aspirativa con aguja fina (PAAF), luego biopsia core que consiste en tomar una muestra del centro de la lesión guiada por ecografía, si fuese necesario, incluyendo inmunohistoquímica para VPH; ambos estudios histológicos son preferibles en vez de una biopsia abierta debido al menor riesgo de diseminación y complicaciones. El siguiente paso incluye estudio endoscópico y biopsias bajo anestesia. El tratamiento de los pacientes con MCCPD, va a depender de factores relacionados con el estadio de la enfermedad: desde cirugía o radioterapia (RT) únicas, cirugía más RT, y en algunos casos quimioterapia. Se recomienda seguimiento clínico frecuente durante los primeros años y con imágenes dentro de los 6 primeros meses postratamiento.

Abstract In adults, a cervical mass detected by physical examination or an imaging study may be the only manifestation of cancer from the head and neck. A delay in the diagnosis affects the prognosis of the disease, so there must be a high index of suspicion. Cervical metastases from unknown primary tumor (CUP) are metastatic tumors in which the diagnostic study failed to identify the primary site of cancer, with predominantly squamous histology. According to some studies, the most frequent origin was the oropharynx, including palatine tonsil and tongue base. Known risk factors are advanced ages, tobacco and alcohol consumption. Currently, human papilloma virus (HPV) infection is playing an increasingly important role as a risk factor, being the cause of between 20-25% of cancers of the head and neck. When confronting a patient with cervical mass it is important to carry out a complete anamnesis and a thorough physical examination to detect any element suggestive of malignancy. Physical examination could be complemented with a flexible nasal endoscopic to evaluate structures that can not be evaluated in the habitual examination. The search for the unknown primary can also be oriented based on lymphatic drainage patterns. Within the complementary evaluations, one can start with a study of images such as computed tomography (CT) or magnetic resonance imaging (MRI) with contrast, and also could consider ultrasound or PET/CT. If the primary can not be defined yet, fine needle aspiration (FNAP) can be the next choice and then a core biopsy that consisting of taking a sample from the center of the ultrasound-guided lesion, if necessary, including immunohistochemistry for HPV; both histological studies are preferable to an open biopsy because of the lower risk of complications. The next step searching for the primary includes endoscopic study and biopsies under anesthesia. Regarding to the management of patients with CUP, it will depend on factors related to the stage of the disease: from surgery or radiotherapy (RT) only, surgery and RT, and in some cases chemotherapy. Frequent clinical follow-up is recommended during the first years and images within the first 6 months after treatment.

Carcinoma escamoso epicraneal metastásico con invasión parenquimatosa cerebral, a propósito de un caso / Metastatic epicranial squamous carcinoma with parenchymal brain invasion, apropos of a case

RESUMEN A nivel mundial se estiman que cada año se diagnostican aproximadamente 650 000 nuevos casos de cáncer escamoso de cabeza y cuello. Ocasionan 300 000 muertes y dos tercios de estos casos se originan en países en vías de desarrollo. Se presentó un caso de un paciente atendido en consulta a causa de crecimiento acelerado de la región frontotemporoparietal derecha, acompañado de sintomatología neurológica correspondiente a una afección funcional de los lóbulos parietal y temporal derecho. Se le realizó exámenes imagenológicos y biopsia por punción de la lesión, lo que arrojó un carcinoma escamoso como variedad histológica de la tumoración (AU).

ABSTRACT It is thought that around 650 000 new cases of head and neck squamous tumors are diagnosed in the world every year. They cause 300 000 deaths and two thirds of these cases are originated in developing countries. We presented the case of a patient who assisted the consultation due to the fast growth of the right frontotemporal parietal region, accompanied with neurological symptomatology corresponding to a functional disorder of the right parietal and temporal lobes. Imaging studies and a biopsy by lesion puncture were performed. It showed a squamous carcinoma as histological variant of the tumor (AU).

Epigallocatechin Gallate Enhances MAL-PDT Cytotoxic Effect on PDT-Resistant Skin Cancer Squamous Cells.

Photodynamic therapy (PDT) has been used to treat certain types of non-melanoma skin cancer with promising results. However, some skin lesions have not fully responded to this treatment, suggesting a potential PDT-resistant phenotype. Therefore, novel therapeutic alternatives must be identified that improve PDT in resistant skin cancer. In this study, we analyzed the cell viability, intracellular protoporphyrin IX (PpIX) content and subcellular localization, proliferation profile, cell death, reactive oxygen species (ROS) detection and relative gene expression in PDT-resistant HSC-1 cells. PDT-resistant HSC-1 cells show a low quantity of protoporphyrin IX and low levels of ROS, and thus a low rate of death cell. Furthermore, the resistant phenotype showed a downregulation of HSPB1, SLC15A2, FECH, SOD2 and an upregulation of HMBS and BIRC5 genes. On the other hand, epigallocatechin gallate catechin enhanced the MAL-PDT effect, increasing levels of protoporphyrin IX and ROS, and killing 100% of resistant cells. The resistant MAL-PDT model of skin cancer squamous cells (HSC-1) is a reliable and useful tool to understand PDT cytotoxicity and cellular response. These resistant cells were successfully sensitized with epigallocatechin gallate catechin. The in vitro epigallocatechin gallate catechin effect as an enhancer of MAL-PDT in resistant cells is promising in the treatment of difficult skin cancer lesions.

[Lung cancer diagnosed by transesophageal ecoendoscopy and fine needle aspiration biopsy]. / Cáncer de pulmón diagnosticado mediante ecoendoscopía transesofágica y biopsia por punción con aguja fina.

Lung cancer is one of the leading causes of death worldwide. Pulmonary nodules located in the vicinity of the mediastinum, retrocardiac, near the aorta or pulmonary vessels, and in front of the spine, may be difficult to access through a percutaneous or bronchoscopic approach. Fine needle aspiration/biopsy guided by transesophageal echoendoscopy (EUS-FNA/FNB) is a minimally invasive method with low morbidity that could allow access to lesions in these places. We present the case of a patient with a solitary pulmonary nodule, in which the diagnosis of lung cancer was obtained by EUS-FNA/FNB.

El cáncer de pulmón es la principal causa de muerte por cáncer en todo el mundo. Los nódulos pulmonares ubicados en proximidad al mediastino, retrocardíacos, cercanos a grandes vasos o por delante de la columna vertebral pueden resultar de difícil acceso por vía percutánea o broncoscópica. La punción aspiración/biopsia con aguja fina guiada por ecoendoscopía transesofágica (EUS-FNA/FNB) es un método mini invasivo con baja morbilidad que permitiría acceder a estas localizaciones. Presentamos el caso de un paciente con nódulo pulmonar solitario, en el que se obtuvo el diagnóstico de cáncer de pulmón mediante EUS-FNA/FNB.

Cáncer de pulmón diagnosticado mediante ecoendoscopia transesofágica y biopsia por punción con aguja fina / Lung cancer diagnosed by transesophageal ecoendoscopy and fine needle aspiration biopsy

El cáncer de pulmón es la principal causa de muerte por cáncer en todo el mundo. Los nódulos pulmonares ubicados en proximidad al mediastino, retrocardíacos, cercanos a grandes vasos o por delante de la columna vertebral pueden resultar de difícil acceso por vía percutánea o broncoscópica. La punción aspiración/biopsia con aguja fina guiada por ecoendoscopía transesofágica (EUS-FNA/FNB) es un método mini invasivo con baja morbilidad que permitiría acceder a estas localizaciones. Presentamos el caso de un paciente con nódulo pulmonar solitario, en el que se obtuvo el diagnóstico de cáncer de pulmón mediante EUS-FNA/FNB.

Lung cancer is one of the leading causes of death worldwide. Pulmonary nodules located in the vicinity of the mediastinum, retrocardiac, near the aorta or pulmonary vessels, and in front of the spine, may be difficult to access through a percutaneous or bronchoscopic approach. Fine needle aspiration/biopsy guided by transesophageal echoendoscopy (EUS-FNA/FNB) is a minimally invasive method with low morbidity that could allow access to lesions in these places. We present the case of a patient with a solitary pulmonary nodule, in which the diagnosis of lung cancer was obtained by EUS-FNA/FNB.