RESUMO
BACKGROUND: The KEYNOTE-048 trial showed that pembrolizumab-based first-line treatment for R/M HNSCC led to improved OS in the PD-L1 CPS ≥ 1 population when compared to the EXTREME regimen. However, the R/M HNSCC real-world population is generally frailer, often presenting with multiple comorbidities, worse performance status and older age than the population included in phase III clinical trials. METHODS: This is a retrospective, single-centre analysis of patients with R/M HNSCC treated with pembrolizumab-based first-line treatment. RESULTS: From February 2021 to March 2023, 92 patients were treated with pembrolizumab-based first-line treatment. Patients treated with pembrolizumab-based chemoimmunotherapy had better ECOG PS and younger age than those treated with pembrolizumab monotherapy. Median PFS and OS were 4 months and 8 months, respectively. PFS was similar among patients treated with pembrolizumab-based chemoimmunotherapy and pembrolizumab monotherapy, while patients treated with pembrolizumab monotherapy had worse OS (log-rank p =.001, HR 2.7). PFS and OS were improved in patients with PD-L1 CPS > = 20 (PFS: log-rank p =.005, HR 0.50; OS: log-rank p =.04, HR 0.57). Patients with higher ECOG PS scores had worse PFS and OS (PFS, log-rank p =.004; OS, log-rank p = 6e-04). In multivariable analysis, ECOG PS2 was associated with worse PFS and OS. CONCLUSIONS: PFS in our real-world cohort was similar to the KEYNOTE-048 reference while OS was numerically inferior. A deeper understanding of clinical variables that might affect survival outcomes of patients with R/M HNSCC beyond ECOG PS and PD-L1 CPS is urgently needed.
Assuntos
Anticorpos Monoclonais Humanizados , Antineoplásicos Imunológicos , Neoplasias de Cabeça e Pescoço , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Antígeno B7-H1 , Estudos Retrospectivos , Antineoplásicos Imunológicos/efeitos adversos , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/induzido quimicamenteRESUMO
INTRODUCTION: The advent of image-guided radiation therapy (IGRT) has recently changed the workflow of radiation treatments by ensuring highly collimated treatments. Artificial intelligence (AI) and radiomics are tools that have shown promising results for diagnosis, treatment optimization and outcome prediction. This review aims to assess the impact of AI and radiomics on modern IGRT modalities in RT. METHODS: A PubMed/MEDLINE and Embase systematic review was conducted to investigate the impact of radiomics and AI to modern IGRT modalities. The search strategy was "Radiomics" AND "Cone Beam Computed Tomography"; "Radiomics" AND "Magnetic Resonance guided Radiotherapy"; "Radiomics" AND "on board Magnetic Resonance Radiotherapy"; "Artificial Intelligence" AND "Cone Beam Computed Tomography"; "Artificial Intelligence" AND "Magnetic Resonance guided Radiotherapy"; "Artificial Intelligence" AND "on board Magnetic Resonance Radiotherapy" and only original articles up to 01.11.2022 were considered. RESULTS: A total of 402 studies were obtained using the previously mentioned search strategy on PubMed and Embase. The analysis was performed on a total of 84 papers obtained following the complete selection process. Radiomics application to IGRT was analyzed in 23 papers, while a total 61 papers were focused on the impact of AI on IGRT techniques. DISCUSSION: AI and radiomics seem to significantly impact IGRT in all the phases of RT workflow, even if the evidence in the literature is based on retrospective data. Further studies are needed to confirm these tools' potential and provide a stronger correlation with clinical outcomes and gold-standard treatment strategies.
Assuntos
Radioterapia (Especialidade) , Radioterapia Guiada por Imagem , Humanos , Radioterapia Guiada por Imagem/métodos , Inteligência Artificial , Estudos Retrospectivos , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia (Especialidade)/métodos , ItáliaRESUMO
Background Recent consensus statements and clinical trials have assessed the value of MRI-guided focused ultrasound surgery for pain palliation of bone metastases; however, a comparison with external beam radiation therapy (EBRT) has not been performed. Purpose To compare safety and effectiveness data of MRI-guided focused ultrasound and EBRT in the treatment of bone metastases. Materials and Methods Participants with painful bone metastases, excluding skull and vertebral bodies, were enrolled in a prospective open-label nonrandomized phase II study between January 2017 and May 2019 and underwent either MRI-guided focused ultrasound or EBRT. The primary end point was the overall response rate at 1-month following treatment, assessed via the numeric rating scale (NRS) for pain (0-10 scale, with zero meaning "no pain" and 10 meaning "the worst pain imaginable"). Secondary end points were improvements at 12-month follow-up in NRS and quality of life (QoL) measures, including the Brief Pain Inventory (BPI), QoL-Questionnaire Cancer-15 Palliative Care (QLQ-C15-PAL), and QoL-Questionnaire Bone Metastases-22 (QLQ-BM22) and analysis of adverse events. Statistical analyses, including linear regression, χ2 test, and Student t test followed the per-protocol principle. Results Among 198 participants, 100 underwent MRI-guided focused ultrasound (mean age, 63 years ± 13 [SD]; 51 women), and 98 underwent EBRT (mean age, 65 years ± 14; 52 women). The overall response rates at 1-month follow-up were 91% (91 of 100) and 67% (66 of 98), respectively, in the focused ultrasound and EBRT arms (P < .001), and complete response rates were 43% (43 of 100) and 16% (16 of 98) (P < .001). The mean baseline NRS score was 7.0 ± 2.1 for focused ultrasound and 6.6 ± 2.4 for EBRT (P = .16); at 1-month follow-up, they were reduced to 3.2 ± 0.3 and 5.1 ± 0.3 (P < .001), respectively. QLQ-C15-PAL for physical function (P = .002), appetite (P < .001), nausea and vomiting (P < .001), dyspnea (P < .001), and QoL (P < .001) scores were lower in the focused ultrasound group. The overall adverse event rates were 15% (15 of 100) after focused ultrasound and 24% (24 of 98) after EBRT. Conclusion MRI-guided focused ultrasound surgery and external beam radiation therapy showed similar improvements in pain palliation and quality of life, with low adverse event rates. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Kelekis in this issue.
Assuntos
Neoplasias Ósseas , Qualidade de Vida , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Cuidados Paliativos/métodos , Estudos Prospectivos , Dor , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/radioterapiaRESUMO
Despite aggressive management consisting of surgery, radiation therapy (RT), and systemic therapy given alone or in combination, a significant proportion of patients with brain tumors will experience tumor recurrence. For these patients, no standard of care exists and management of either primary or metastatic recurrent tumors remains challenging.Advances in imaging and RT technology have enabled more precise tumor localization and dose delivery, leading to a reduction in the volume of health brain tissue exposed to high radiation doses. Radiation techniques have evolved from three-dimensional (3-D) conformal RT to the development of sophisticated techniques, including intensity modulated radiation therapy (IMRT), volumetric arc therapy (VMAT), and stereotactic techniques, either stereotactic radiosurgery (SRS) or stereotactic radiotherapy (SRT). Several studies have suggested that a second course of RT is a feasible treatment option in patients with a recurrent tumor; however, survival benefit and treatment related toxicity of reirradiation, given alone or in combination with other focal or systemic therapies, remain a controversial issue.We provide a critical overview of the current clinical status and technical challenges of reirradiation in patients with both recurrent primary brain tumors, such as gliomas, ependymomas, medulloblastomas, and meningiomas, and brain metastases. Relevant clinical questions such as the appropriate radiation technique and patient selection, the optimal radiation dose and fractionation, tolerance of the brain to a second course of RT, and the risk of adverse radiation effects have been critically discussed.
Assuntos
Neoplasias Encefálicas , Neoplasias Cerebelares , Radiocirurgia , Radioterapia Conformacional , Reirradiação , Humanos , Reirradiação/métodos , Recidiva Local de Neoplasia/radioterapia , Recidiva Local de Neoplasia/cirurgia , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/cirurgia , Radioterapia Conformacional/métodos , Neoplasias Cerebelares/cirurgiaRESUMO
OBJECTIVE: To investigate the predictive role of diffusion-weighted magnetic resonance imaging (DW-MRI) in the assessment of response to total neoadjuvant therapy (TNT) in patients with locally advanced rectal cancer (LARC). METHODS: In this single-center retrospective study, patients with LARC who underwent staging MRI and TNT were enrolled. MRI-based staging, tumor volume, and DWI-ADC values were analyzed. Patients were classified as complete responders (pCR) and non-complete responders (non-pCR), according to post-surgical outcome. Pre-treatment ADC values were compared to pathological outcome, post-treatment downstaging, and reduction of tumor volume. The diagnostic accuracy of DWI-ADC in differentiating between pCR and non-pCR groups was calculated with receiver operating characteristic (ROC) analysis. RESULTS: A total of 36 patients were evaluated (pCR, n = 20; non-pCR, n = 16). Pre-treatment ADC values were significantly different between the two groups (p = 0.034), while no association was found between pre-TNT tumor volume and pathological response. ADC values showed significant correlations with loco-regional downstaging after therapy (r = -0.537, p = 0.022), and with the reduction of tumor volume (r = -0.480, p = 0.044). ADC values were able to differentiate pCR from non-pCR patients with a sensitivity of 75% and specificity of 70%. CONCLUSIONS: ADC values on pre-treatment MRI were strongly associated with the outcome in patients with LARC, both in terms of pathological response and in loco-regional downstaging after TNT, suggesting the use of DW-MRI as a potential predictive tool of response to therapy. KEY POINTS: ⢠ADC values of pre-TNT MRI examinations of patients with LARC were significantly associated with a pathological complete response (pCR) and with post-treatment regression of TNM staging. ⢠An ADC value of 1.042 ×10-3 mm2/s was found to be the optimal cutoff value for discriminating between pCR and non-pCR patients, with a sensitivity of 75% and specificity of 70%. ⢠DW-MRI proved to have a potential predictive role in the assessment of response to therapy in patients with LARC, throughout the analysis of ADC map values.
Assuntos
Imagem de Difusão por Ressonância Magnética , Neoplasias Retais , Humanos , Imagem de Difusão por Ressonância Magnética/métodos , Terapia Neoadjuvante , Estudos Retrospectivos , Neoplasias Retais/terapia , Neoplasias Retais/tratamento farmacológico , Imageamento por Ressonância Magnética , Quimiorradioterapia , Resultado do TratamentoRESUMO
PURPOSE: The present study examined the longitudinal trajectories, through hierarchical modeling, of quality of life among patients with head and neck cancer, specifically symptoms burden, during radiotherapy, and in the follow-up period (1, 3, 6, and 12 months after completion of radiotherapy), through the M.D. Anderson Symptom Inventory Head and Neck questionnaire, formed by three factors. Furthermore, analyses were conducted controlling for socio-demographic as well as clinical characteristics. METHODS: Multi-level mixed-effects linear regression was used to estimate the association between quality of life and time, age, gender, household, educational level, employment status, ECOG performance status, human papilloma virus (HPV) status, surgery, chemotherapy, alcohol intake, and smoking. RESULTS: Among the 166 participants, time resulted to be a predictor of all the three questionnaire factors, namely, general and specific related symptoms and interference with daily life. Moreover, regarding symptom interference with daily activities factor, HPV-positive status played a significant role. Considering only HPV-negative patients, only time predicted patients' quality of life. Differently, among HPV-positive patients, other variables, such as gender, educational level, alcohol use, surgery, age at diagnosis, employment status, and ECOG status, resulted significant. CONCLUSION: It was evident that quality of life of patients with head and neck cancer declined during RT, whereas it slowly improved after ending treatment. Our results clarified the role of some socio-demographic and clinical variables, for instance, HPV, which would allow to develop treatments tailored to each patient.
Assuntos
Neoplasias de Cabeça e Pescoço , Infecções por Papillomavirus , Humanos , Qualidade de Vida , Estudos Prospectivos , Neoplasias de Cabeça e Pescoço/radioterapia , OncologiaRESUMO
OBJECTIVE: To assess the accuracy of pathological diagnosis by transvaginal ultrasound-guided biopsy versus surgery in patients with suspicious primary advanced tubo-ovarian carcinoma. The Feasibility, adequacy, and safety of the procedure were also evaluated. METHODS: Consecutive women with pre-operative suspicious primary advanced tubo-ovarian carcinoma presenting between July 2019 and September 2021 were enrolled. Accuracy was calculated including only cases who underwent surgery. Feasibility was defined as the number of cases in which ultrasound-guided biopsy was possible according to tumor characteristics (morphology and site). Adequacy was defined as the number of conclusive diagnoses out of the samples collected. Safety was defined by the number of major complications which were defined as hospitalization, surgery, and/or blood transfusion. RESULTS: A total of 278 patients were eligible for the study; 158 were enrolled, while 120 were excluded for logistic reasons or patient refusal. Ultrasound-guided biopsy was not feasible in 30 (19%) patients. The samples obtained in the remaining 128 patients were all adequate (100%), and no major complications were noted. A total of 26 (20%) patients started neoadjuvant chemotherapy on the basis of the diagnosis obtained by ultrasound, whereas 102 (80%) patients underwent surgery. Accuracy of ultrasound-guided biopsy versus surgery was 94% (96/102), with six false negative cases at ultrasound (6%). Site (prevesical peritoneum) and size (<8 mm) of the nodules resulted as major predictive factors for ultrasound-guided biopsy failure (false negative). Ultrasound-guided biopsy correctly identified 86 primary invasive tubo-ovarian carcinomas and 10 metastatic tumors. CONCLUSION: Ultrasound-guided biopsy is a feasible, safe, and accurate method to provide histological diagnosis in suspicious advanced tubo-ovarian cancer patients.
Assuntos
Carcinoma , Neoplasias Ovarianas , Humanos , Feminino , Ultrassonografia , Biópsia Guiada por Imagem/métodos , Neoplasias Ovarianas/diagnóstico por imagem , Neoplasias Ovarianas/cirurgia , Neoplasias Ovarianas/patologia , Ultrassonografia de Intervenção/métodosRESUMO
OBJECTIVES: To report clinical outcomes of relapsed oropharyngeal squamous cell carcinoma (OPSCC) after definitive intensity-modulated (chemo)radiotherapy [(C)RT]. MATERIALS AND METHODS: Data for all relapsed patients treated for OPSCC with definitive (C)RT between 2010 and 2016 were collected. Primary end-point was post-failure survival (PFS). RESULTS: Overall, 273 OPSCC patients completed definitive (C)RT. Of these, 42 cases (n = 26 human papilloma virus (HPV)-negative; n = 16 HPV-positive) had relapsed (n = 23 persistent disease; n = 19 recurrent disease) and were included in the final analysis. Two-year PFS for the entire population was 30.6%; 20.5% for HPV-negative and 43.8% for HPV-positive patients. Salvage curative surgery was associated with a significantly higher 2 years PFS rate (56.2%) compared with palliative treatment (22.9%) and best supportive care (0%) (p < 0.001). A positive trend in 2 years PFS was recorded in the early complete response cases (49.5%) versus patients who did not achieve a complete response within 3 months of the end of (C)RT (23.0%) (p = 0.11). CONCLUSION: A higher PFS rate is achieved when relapsed OPSCC cases are treated with salvage curative intent. HPV-positive disease and early complete response within 3 months from the end of (C)RT may be related to better PFS.
Assuntos
Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Neoplasias Orofaríngeas , Infecções por Papillomavirus , Humanos , Infecções por Papillomavirus/complicações , Neoplasias Orofaríngeas/tratamento farmacológico , Neoplasias Orofaríngeas/radioterapia , Carcinoma de Células Escamosas de Cabeça e Pescoço , Neoplasias Bucais/complicações , Papillomavirus Humano , Doença Crônica , Neoplasias de Cabeça e Pescoço/complicações , Prognóstico , Estudos RetrospectivosRESUMO
OBJECTIVES: To prospectively investigate changes in M.D. Anderson Dysphagia Inventory (MDADI) scores in patients affected by naso- and oropharynx cancer after definitive radiochemotherapy (ChemoRT) using swallowing organs at risk (SWOARs)-sparing IMRT. METHODS: MDADI questionnaires were collected at baseline and at 6 and 12 months after treatment. MDADI scores were categorized as follows: ≥ 80 "optimal," 80-60 "adequate," < 60 "poor" deglutition-related quality of life (QoL) group, and dichotomized as "optimal" vs "adequate/poor" for the analysis. A mean MDADI composite (MDADI-C) change of 10 points was considered as minimal clinically important difference (MCID). RESULTS: Sixty-three patients were enrolled of which 47 were considered for the analysis. At baseline, 26 (55%) were "optimal" and 21 (45%) were "adequate/poor." The mean baseline MDADI-C score was 93.6 dropping to 81 at 6 months (p = 0.013) and slightly rising to 85.5 at 12 months (p = 0.321) for the "optimal" group. Indeed, the mean baseline MDADI-C score was 64.3 rising to 77.5 at 6 months (p = 0.006) and stabilizing at 76 at 12 months (p = 0.999) for the "adequate/poor" group. A statistically significant but not clinically relevant worsening of the MDADI-C score was reported for the "optimal" group, whereas both a statistically significant and clinically meaningful improvement of the MDADI-C score were reported for the "adequate/poor" group from before to post-treatment. CONCLUSION: Our results suggest a doubly clinical benefit of dose optimization to SWOARs to minimize the RT sequalae in patients with a baseline "optimal" deglutition-related QoL and to recover from cancer dysphagia in those with a baseline "adequate/poor" deglutition-related QoL.
Assuntos
Transtornos de Deglutição , Neoplasias de Cabeça e Pescoço , Radioterapia de Intensidade Modulada , Humanos , Transtornos de Deglutição/etiologia , Estudos Prospectivos , Qualidade de Vida , Deglutição , Radioterapia de Intensidade Modulada/efeitos adversos , Órgãos em Risco , Neoplasias de Cabeça e Pescoço/complicações , Neoplasias de Cabeça e Pescoço/radioterapia , Medidas de Resultados Relatados pelo Paciente , OncologiaRESUMO
PURPOSE: This study aimed to establish a nomogram for predicting overall survival (OS) in oropharyngeal cancer patients treated with curative (chemo)radiotherapy. MATERIALS AND METHODS: The dynamic nomogram was constructed on 273 patients with oropharyngeal squamous cell carcinoma treated in a Tertiary Head and Neck Cancer Unit. The clinical features that were previously reported to be associated with OS were analyzed. The performance of the nomogram was assessed using concordance index (C-index) and calibration curves. RESULTS: The nomogram incorporated three explanatory variables derived from a decision tree approach including HPV status, N classification according to 8th edition TNM and early response to (chemo)radiotherapy. The nomogram was capable to predict OS with a validation C-index of 0.768. The proposed stratification in risk groups allowed significant distinction between Kaplan-Meier curves for OS outcome (p < 0.0001). CONCLUSIONS: The nomogram provided an accurate evaluation of OS for oropharyngeal cancer patients treated with curative (chemo)radiotherapy.
Assuntos
Neoplasias de Cabeça e Pescoço , Neoplasias Orofaríngeas , Humanos , Nomogramas , Prognóstico , Estadiamento de Neoplasias , Neoplasias Orofaríngeas/terapia , Neoplasias de Cabeça e Pescoço/terapia , QuimiorradioterapiaRESUMO
BACKGROUND AND PURPOSE: The Young Section of the Italian Association of Radiotherapy and Clinical Oncology (yAIRO) circulated an online questionnaire survey among residents currently enrolled within Italian radiotherapy residency schools to investigate the profiles, motivations, knowledge of the radiotherapy discipline, organizations and the needs of younger members. MATERIALS AND METHODS: The survey was developed by the yAIRO steering committee and included questions about the demographic characteristics of the residents (Profile A), the background of their clinical experience during the school of medicine and national residency admission test performance (Profile B) and the residents' knowledge of the scientific associations active in the field of radiotherapy (Profile C). RESULTS: Out of 400 residents actually in training, 134 responded to the questionnaire (response rate 33.5%). According to most of the residents, radiotherapy was not adequately studied during the medical school (n. 95; 71%) and an Internship in Radiotherapy was not mandatory (n. 99; 74%). Only a minority of the residents had chosen to complete a master's degree thesis in radiotherapy (n. 12; 9%). A low percentage of the residents stated that they were aware of the Italian Association of Radiotherapy and Clinical Oncology (AIRO), its young section (yAIRO) and the European Society for Radiotherapy and Oncology (ESTRO) when they were in School of Medicine (respectively, 11%, 7% and 13%). CONCLUSIONS: The results of the survey require a profound reflection on the current teaching methods of Radiation Oncology in our country, highlighting the need for a better integration in the framework of the School of Medicine core curriculum.
Assuntos
Internato e Residência , Radioterapia (Especialidade) , Humanos , Radioterapia (Especialidade)/educação , Radio-Oncologistas , Oncologia/educação , Inquéritos e Questionários , CurrículoRESUMO
Target volume delineation in the radiation treatment of nasopharyngeal cancer is challenging due to several reasons such as the complex anatomy of the site, the need for the elective coverage of definite anatomical regions, the curative intent of treatment and the rarity of the disease, especially in non-endemic areas. We aimed to analyze the impact of educational interactive teaching courses on target volume delineation accuracy between Italian radiation oncology centers. Only one contour dataset per center was admitted. The educational course consisted in three parts: (1) The completely anonymized image dataset of a T4N1 nasopharyngeal cancer patient was shared between centers before the course with the request of target volume and organs at risk delineation; (2) the course was held online with dedicated multidisciplinary sessions on nasopharyngeal anatomy, nasopharyngeal cancer pattern of diffusion and on the description and explanation of international contouring guidelines. At the end of the course, the participating centers were asked to resubmit the contours with appropriate corrections; (3) the pre- and post-course contours were analyzed and quantitatively and qualitatively compared with the benchmark contours delineated by the panel of experts. The analysis of the 19 pre- and post-contours submitted by the participating centers revealed a significant improvement in the Dice similarity index in all the clinical target volumes (CTV1, CTV2 and CTV3) passing from 0.67, 0.51 and 0.48 to 0.69, 0.65 and 0.52, respectively. The organs at risk delineation was also improved. The qualitative analysis consisted in the evaluation of the inclusion of the proper anatomical regions in the target volumes; it was conducted following internationally validated guidelines of contouring for nasopharyngeal radiation treatment. All the sites were properly included in target volume delineation by >50% of the centers after correction. A significant improvement was registered for the skull base, the sphenoid sinus and the nodal levels. These results demonstrated the important role that educational courses with interactive sessions could have in such a challenging task as target volume delineation in modern radiation oncology.
Assuntos
Neoplasias Nasofaríngeas , Radioterapia (Especialidade) , Humanos , Neoplasias Nasofaríngeas/radioterapia , Carcinoma Nasofaríngeo/radioterapia , Nasofaringe , Radioterapia (Especialidade)/educação , Planejamento da Radioterapia Assistida por Computador/métodosRESUMO
Background and Objective: Exclusive radiotherapy, including external beam radiotherapy (EBRT) and interventional radiotherapy/brachytherapy (IRT/BT), with concurrent cisplatin-based chemotherapy, represents the standard of care in patients with locally advanced cervical cancer (LACC). The emerging topic of vaginal toxicity has become a key endpoint in LACC management, although different approaches and non-standardized procedures were available. Our aim was to analyze a nationwide study of the attitudes of Italian gynecological radiation oncology teams in the management of LACC patients' vaginal toxicities. Methods: A nationwide survey of radiation oncologists specializing in the treatment of gynecological malignancies was performed, using the free SurveyMonkey platform, consisting of 26 items. The questionnaire was proposed by the Italian Association of Radiation Oncologists (AIRO) gynecological working group to all 183 Italian radiation oncology institutions, as per AIRO's website. Results: Fifty-eight questionnaires (31%) were completed and returned. The assessment of acute and late vaginal toxicities was systematic in 32 (55.2%) and 26 (44.8%) centers, respectively. In the case of EBRT, 70.7% of centers, according to the contouring and treatment plan data, did not contour the vagina as an organ at risk (OAR). Vaginal dose constraints were heterogeneous for both EBRT and IRT/BT. Local treatment to prevent vaginal toxicity was prescribed by 60.3% of radiation oncologists, mostly vaginal hyaluronic acid cream, and one center recommended vaginal estrogen preparations. During follow-up visits, vaginal toxicity was considered an issue to be investigated always (n = 31) or in sexually active women only (n = 11). Conclusions: This survey showed that wide variation exists with regard to recording and treating vaginal toxicity after exclusive chemoradiation for cervical cancer, underscoring the need to develop more comprehensive guidelines for contouring e-dose reporting of the vagina, so as to implement clinical approaches for vaginal toxicity.
Assuntos
Braquiterapia , Neoplasias dos Genitais Femininos , Ginecologia , Radioterapia (Especialidade) , Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/patologia , Radio-Oncologistas , Oncologia , Braquiterapia/métodos , Inquéritos e QuestionáriosRESUMO
Ovarian cancer (OC) remains a fatal malignancy because most patients experience recurrent disease, which is resistant to chemotherapy. The outcomes for patients with platinum-resistant OC are poor, response rates to further chemotherapy are low and median survival is lower than 12 months. The complexity of platinum-resistant OC, which comprises a heterogeneous spectrum of diseases, is indeed far from being completely understood. Therefore, comprehending tumors' biological behaviour to identify reliable biomarkers, which may predict responses to therapies, is a demanding challenge to improve OC management. In the age of precision medicine, efforts to overcome platinum resistance in OC represent a dynamic and vast field in which innovative drugs and clinical trials rapidly develop. This review will present the exceptional biochemical environment implicated in OC and highlights mechanisms of chemoresistance. Furthermore, innovative molecules and new therapeutic opportunities are presented, along with currently available therapies and ongoing clinical trials.
Assuntos
Biomarcadores Tumorais , Carcinoma Epitelial do Ovário , Resistencia a Medicamentos Antineoplásicos , Animais , Carcinoma Epitelial do Ovário/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Feminino , HumanosRESUMO
INTRODUCTION: The aim of this study is to assess the clinical reproducibility and the potential oncological validity of the molecular information provided by the immunohistochemistry (IHC) to properly stratify the endometrial cancer patients. METHODS: Retrospective IHC analyses were conducted in a large series of 778 pre-operative uterine-confined ECs, studying the presence/absence of MLH1, MSH2, MSH6 and PMS2 to define the mismatch repair (MMR) stable or instable phenotype; the presence of p53 mutations and other molecular features. The molecular profile was correlated with histological, clinical and prognostic data. RESULTS: Based on IHC assessment, we defined 3 EC populations: stable MMR patients (MMRs), instable patients (MMRi) and p53 mutated patients (p53+). Our result demonstrated that the IHC stratification statistically correlated with the most relevant pathologic-clinical features: FIGO stage (p < 0.001), grading (p < 0.001), histotype (p < 0.001), presence of LVSI (p < 0.001), myometrial invasion and tumor dimension (p = 0.003 for both). These 3 IHC populations statistically reflected the EC risk class ESGO-ESMO-ESP classification 2021 (p < 0.001). These results were also confirmed in the Kaplan-Meier curves in terms of overall survival (OS) and disease-free survival (DFS) (p < 0.0001). The multivariate analyses demonstrated that absence of estrogen receptor (ER) impacted the OS (p = 0.011) and, the Age > 60 years and the ER-status the DFS (p = 0.041 and p = 0.004). CONCLUSION: In this large series, we demonstrated that the pragmatic and systematic use of IHC may have an important role to properly stratify, in terms of histological features and clinical outcomes, the EC patients.
Assuntos
Neoplasias do Endométrio , Proteína Supressora de Tumor p53 , Reparo de Erro de Pareamento de DNA , Neoplasias do Endométrio/patologia , Feminino , Humanos , Endonuclease PMS2 de Reparo de Erro de Pareamento/genética , Proteína 1 Homóloga a MutL/genética , Reprodutibilidade dos Testes , Estudos Retrospectivos , Proteína Supressora de Tumor p53/genéticaRESUMO
OBJECTIVES: The role of radiotherapy (RT) for oligometastases is currently established in different oncological settings but data on salivary gland cancer (SGC) are lacking. We evaluated the role of RT in oligometastatic SGC patients, focusing on stereotactic body radiation therapy (SBRT). MATERIALS AND METHODS: We performed a retrospective, multicentric study of oligometastatic SGC treated with palliative RT or SBRT. Endpoints included response evaluation and local control (LC). RESULTS: Between 2006 and 2016, 64 patients were collected from 9 Italian Cancer Centers, on behalf of the Italian Association of Radiotherapy and Clinical Oncology (AIRO) Head and Neck Working Group. 37 patients (57.8%) were suffering from adenoid cystic carcinoma (ACC) and 27 patients (42.2%) had non-ACC. Thirty-four patients underwent palliative RT (53,1%), and 30 received SBRT (46,9%). Most common metastatic sites were bone for palliative RT and lung for SBRT. Among patients treated with SBRT, an objective response or a stability was observed in all treated lesions. After a median follow-up of 29.2 months (range 2.3-117.1), LC at 12 months was 57.5% for patients treated with SBRT and was higher in ACC subgroup. CONCLUSION: We confirmed the potential role of SBRT in the management of oligometastatic SGC patients to control limited burden of disease considering the absence of effective systemic therapies.
Assuntos
Carcinoma Adenoide Cístico , Neoplasias Pulmonares , Radiocirurgia , Neoplasias das Glândulas Salivares , Carcinoma Adenoide Cístico/radioterapia , Carcinoma Adenoide Cístico/cirurgia , Humanos , Neoplasias Pulmonares/patologia , Radiocirurgia/efeitos adversos , Estudos Retrospectivos , Neoplasias das Glândulas Salivares/radioterapia , Neoplasias das Glândulas Salivares/cirurgia , Glândulas Salivares/patologiaRESUMO
STUDY OBJECTIVE: To identify preoperative/intraoperative patient and tumor characteristics associated with an increased risk of tumor spillage during minimally invasive surgery (MIS) for early-stage ovarian cancer (OC). The secondary end point was to develop a score system able to estimate the risk of tumor rupture during MIS. DESIGN: Retrospective observational study. SETTING: Patients with International Federation of Gynecology and Obstetrics stage I OC. PATIENTS: Patients aged ≥18 years old, with International Federation of Gynecology and Obstetrics stage IA to IC1 OC of any histology. INTERVENTIONS: Preoperative and intraoperative characteristics of patients treated with MIS for early-stage OC at Policlinico Universitario Agostino Gemelli, IRCCS in Rome, Italy, from January 1, 2001, to December 31, 2017, were collected. MEASUREMENTS AND MAIN RESULTS: A total of 151 patients were included. Previous pelvic surgery was more represented in patients with nonruptured tumors (46.0% vs 63.4%; p = .042). In addition, a larger tumor diameter (p <.001), a higher body mass index (p = .032), ultrasound characteristics (p = .029), and adhesions to large bowel (14% vs 2.0%; p = .003), uterus (44% vs 6.9%; p <.001), contralateral ovary (8.0% vs 0%; p = .004), ovarian fossa (64% vs 14.9%; p <.001), and pouch of Douglas peritoneum (32% vs 4.0%; p <.001) increased rupture rate. At multivariate analysis, a larger tumor diameter (p <.001) and adhesions to ovarian fossa peritoneum (p = .007) were independently associated with intraoperative cancer spillage and included in the score calculation. A disease-free survival (DFS) difference between the rupture group and the no-rupture group was detected (5-year DFS, 74.9% vs 94.4%; p = .011), with superimposable overall survival (5-year overall survival, 91.2% vs 97.9%; p = .089). CONCLUSION: Some preoperative/intraoperative characteristics increase the risk of tumor rupture during MIS for early-stage OC. A laparoscopic predictive model of capsule disruption could be considered to intraoperatively tailor surgical approach to prevent tumor spillage and avoid affecting patient's DFS.
Assuntos
Laparoscopia , Neoplasias Ovarianas , Adolescente , Adulto , Carcinoma Epitelial do Ovário/cirurgia , Feminino , Humanos , Laparoscopia/efeitos adversos , Estadiamento de Neoplasias , Neoplasias Ovarianas/patologia , Estudos RetrospectivosRESUMO
OBJECTIVE: First-line therapy for metastatic squamous cell carcinoma of the head and neck (R/M HNSCC) has been revolutionized by the introduction of anti-checkpoint monoclonal antibodies, which have shown a significant improvement in overall survival (OS) gaining approval in a first line setting. Efficacy and safety of first-line weekly chemotherapy, compared to 3-weeks treatment, was retrospectively evaluated in a frail patient population with R/M HNSCC with the aim to evaluate its role as part of a personalized first-line approach. METHODS: A total of 124 patients with locally incurable R/M HNSCC receiving weekly (21) or three-weekly (103) chemotherapy plus cetuximab in a first line setting from December 2010 to September 2020 were retrospectively reviewed. Treatment outcomes in terms of objective response rate (ORR), progression-free survival (PFS), overall survival (OS) and toxicities were analysed. RESULTS: Patients in the three-week subgroup were ECOG PS 0 (39) and 1 (64) while patients in weekly group (21) were all PS 2. No significant differences were reported in terms of age, sex, smoking and previous alcohol abuse considering the two distinct subgroups. Moreover, no statistically significant difference was found in PFS and OS between the two treatment subgroups. The response rate was 35% (36 patients) and 34% (7 patients) in three-week and weekly treatment group, respectively. Seventy patients (68%) in the three-week group experienced chemotherapy-related toxicities, predominantly G3. In the weekly group a predominantly low-grade toxicity was found in a lower number of patients (52%). CONCLUSION: The weekly schedule appears to be an active and safe strategy in frail patients with R/M HNSCC. Based on these data, a weekly schedule could be considered as a first line treatment in all frail patients excluded from pembrolizumab treatment and a study on the combination of weekly chemotherapy and immunotherapy should be performed.
Assuntos
Idoso Fragilizado , Neoplasias de Cabeça e Pescoço , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica , Cetuximab/uso terapêutico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Humanos , Imunoterapia , Recidiva Local de Neoplasia/tratamento farmacológico , Estudos RetrospectivosRESUMO
BACKGROUND: Phase 3 randomized clinical trials have been designed to compare secondary cytoreductive surgery followed by systemic therapy with systemic therapy alone for management of patients with recurrent ovarian cancer. This study aimed to compare differences in clinical outcomes between these two treatment approaches. METHODS: The PRISMA statement was applied. Only phase 3 randomized clinical trials were included in the final analysis. RESULTS: Three randomized clinical trials (n = 1250 patients) were identified. Secondary cytoreductive surgery was associated with significantly better progression-free survival (PFS) improvement than systemic therapy alone (hazard ratio [HR], 95% CI, 0.61-0.78; p < 0.001). The PFS benefit was greater for the complete resection subpopulation (HR, 0.56; 95% CI, 0.48-0.66; p < 0.001). The HR of overall survival (OS) was similar between the groups (HR, 0.93; 95% CI, 0.78-1.10; p = 0.37), but it was 0.73 (95% CI, 0.59-0.91) in favor of the complete resection subpopulation. CONCLUSION: This meta-analysis showed secondary cytoreductive surgery as superior to systemic therapy alone in terms of PFS. The PFS and OS benefits were particularly observed for complete surgical resection. The impact on OS in the general population remains to be proven.
Assuntos
Procedimentos Cirúrgicos de Citorredução , Neoplasias Ovarianas , Carcinoma Epitelial do Ovário , Intervalo Livre de Doença , Feminino , Humanos , Recidiva Local de Neoplasia/cirurgia , Neoplasias Ovarianas/cirurgia , Intervalo Livre de ProgressãoRESUMO
OBJECTIVE: The therapeutic role of pelvic and para-aortic lymphadenectomy in surgical staging of apparent early-stage epithelial ovarian cancer (eEOC) is still under debate. The aim of this study was to evaluate the potential therapeutic role of systematic lymphadenectomy in patients with eEOC. METHODS: Multi-center retrospective cohort study, comparing women with apparent eEOC who underwent comprehensive bilateral pelvic and para-aortic lymphadenectomy (defined as ≥20 lymph nodes) versus patients receiving no lymphadenectomy or lymph node sampling, from 05/1985 to 12/2016. Patients with bulky nodes at CT-scan and those without complete intra-peritoneal surgical staging were excluded. Only patients who received at least 3 cycles of platinum-based adjuvant chemotherapy were included. RESULTS: Out of 2559 patients with FIGO stage IA-IIIA1 ovarian cancer, 639 (25.0%) met inclusion criteria. 360 (56.3%) underwent comprehensive lymphadenectomy, 150 (23.5%) lymph node sampling and 129 (20.2%) no lymphadenectomy. Patients who underwent comprehensive lymphadenectomy were younger (p < 0.001), experienced a higher number of severe post-operative complications (p = 0.008) and had a longer time to start chemotherapy (p = 0.034). There was no difference in intra-operative complications. Median follow-up was 63 months (range, 5-342). The 5-year disease-free survival (DFS) was 79.7% vs. 76.5% vs. 68.3% (p = 0.006), and 5-year overall survival (OS) was 92.3% vs. 94.5% vs. 89.8% (p = 0.165) in women who received comprehensive lymphadenectomy vs. lymph node sampling vs. no lymphadenectomy, respectively. Lymphadenectomy represented an independent factor for DFS improvement, HR 0.52 (95%CI 0.37-0.73) (p < 0.001). CONCLUSION: Pelvic and para-aortic lymphadenectomy in surgical staging of eEOC improves DFS for the price of increasing post-operative complications and time to chemotherapy but does not affect OS. Better understanding of tumor biology may help to identify those patients in whom lymphadenectomy should still play a role.