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PURPOSE: Orbital rhabdomyosarcoma is a rare soft tissue sarcoma in childhood but with a good prognosis. Treatment usually includes surgery, chemotherapy, and radiotherapy. This study aimed to evaluate long-term alterations in teeth and cranial bones in children, adolescents, and young adults after oncologic treatment for childhood orbital rhabdomyosarcoma. METHOD: This was a cross-sectional study that evaluated patients treated for orbital rhabdomyosarcoma between 1988 and 2011. Demographic, clinical, and treatment data were collected during the study period; also, panoramic radiographs, cephalometric study, and photographs of the face were taken. RESULTS: Eight long-term survivors were studied. Of those, 50% were male, 75% had less than 5 years of treatment, and 88% had only one of the orbits affected by the tumor. Regarding treatment, 50% received 50.4 Gy of radiotherapy in the orbit; the chemotherapy included vincristine, actinomycin D, and cyclophosphamide in 75% of the cases and also ifosfamide and etoposide in 25%. The children presented craniofacial alterations, mainly when radiotherapy occurred between 0 and 5 years old (p = 0.01). The mandibles also showed dental alterations, probably due to chemotherapy. CONCLUSION: In conclusion, orbital RMS patients treated with chemoradiotherapy, important dental, and facial bone alterations were found. The most significant were in the maxilla and close to the irradiation field. Dental and mandibular bone alterations were also found, indicating the probable chemotherapy action, as this region was not included in the irradiation field.
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Neoplasias Orbitales , Rabdomiosarcoma , Humanos , Masculino , Femenino , Estudios Transversales , Rabdomiosarcoma/terapia , Adolescente , Neoplasias Orbitales/terapia , Niño , Preescolar , Adulto Joven , Protocolos de Quimioterapia Combinada Antineoplásica , Quimioradioterapia/métodos , Quimioradioterapia/efectos adversos , Lactante , Supervivientes de Cáncer/estadística & datos numéricos , Ciclofosfamida/administración & dosificación , Vincristina/administración & dosificaciónAsunto(s)
Quimioradioterapia , Neoplasias Pulmonares , Carcinoma Pulmonar de Células Pequeñas , Humanos , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/terapia , Carcinoma Pulmonar de Células Pequeñas/radioterapia , Carcinoma Pulmonar de Células Pequeñas/terapia , Carcinoma Pulmonar de Células Pequeñas/patología , Quimioradioterapia/métodos , Fraccionamiento de la Dosis de RadiaciónRESUMEN
BACKGROUND: Immunotherapy provided significant survival benefits for recurrent and metastatic patients with head and neck cancer. These improvements could not be reproduced in patients treated with curative-intent chemoradiotherapy (CRT) and the optimal radio-immunotherapy (RIT) concepts have yet to be designed. Exploration and analysis of the pre-therapeutic immune status of these patients and the changes occurring during the treatment course could be crucial in rationally designing future combined treatments. METHODS: Blood samples were collected from a cohort of 25 head and neck cancer patients treated with curative-intended (C)-RT prior to therapy, after the first week of treatment, and three months after treatment completion. Peripheral blood mononuclear cells (PBMCs) or all nucleated blood cells were isolated and analyzed via flow cytometry. RESULTS: At baseline, patients showed reduced monocyte and lymphocyte counts compared to healthy individuals. Although overall CD8+ T-cell frequencies were reduced, the proportion of memory subsets were increased in patients. Radiotherapy (RT) treatment led to a further increase in CD8+ effector memory T-cells. Among myeloid populations, tumor-promoting subsets became less abundant after RT, in favor of pro-inflammatory cells. CONCLUSION: The present study prospectively demonstrated a complex interplay and distinct longitudinal changes in the composition of lymphocytic and myeloid populations during curative (C)-RT of head and neck cancer. Further validation of this method in a larger cohort could allow for better treatment guidance and tailored incorporation of immunotherapies (IT) in the future.
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Quimioradioterapia , Neoplasias de Cabeza y Cuello , Células Mieloides , Humanos , Neoplasias de Cabeza y Cuello/terapia , Neoplasias de Cabeza y Cuello/inmunología , Quimioradioterapia/métodos , Masculino , Persona de Mediana Edad , Femenino , Anciano , Células Mieloides/inmunología , Estudios Longitudinales , Adulto , Estudios ProspectivosRESUMEN
BACKGROUND: Radiotherapy (RT) is used in head and neck squamous cell carcinoma (HNSCC) with excellent effectiveness, but it is burdened by important side effects, which may negatively impact patients' quality of life (QoL). In particular when associated with chemotherapy (CT), that has a radiosensitising effect (and its own toxicities), it is responsible for several adverse events, causing social discomfort and lower QoL, in patients who are already experiencing several tumor-related discomforts. Prehabilitation is a healthcare intervention consisting of several specialist visits prior to the start of treatment, with the aim of improving the patient's health status, resolving symptoms that interfere with treatment and impact QoL, and finally to better avoid or overcome complications. Of all cancer patients, HNSCC patients are among those who could benefit most from prehabilitation, both because of the high number of symptoms and toxicities and their difficult management. Despite this and the emerging data, prehabilitation is not often considered for the majority of patients undergoing (C)RT. In this review, we tried to understand what are the main areas in which interventions can be made prior to the (C)RT start, the possible side effects of the treatment, the effectiveness in their prevention and management, and the impact that prehabilitation may have in adherence to therapy and on the principal survival outcomes, providing important guidance for the planning of future studies. EVIDENCES AND CONCLUSIONS: Although there is no strong data evaluating multidisciplinary prehabilitation strategies, evidence shows that optimizing the patient's health status and preventing possible complications improve the QoL, reduce the incidence and severity of adverse events, and improve treatment adherence. While cardiology prehabilitation is of paramount importance for all patients undergoing concomitant CRT in the prevention of possible side effects, the remaining interventions are useful independently of the type of treatment proposed. Geriatricians have a key role in both elderly patients and younger patients characterized by many comorbidities to comprehensively assess health status and indicate which treatment may be the best in terms of risk/benefit ratio. Collaboration between nutritionists and phoniatrics, on the other hand, ensures adequate nutritional intake for the patient, where possible orally. This is because optimizing both body weight and muscle mass and qualities has been shown to impact key survival outcomes. Finally, HNSCC patients have the second highest suicide rate, and the disease has side effects such as pain, dysfiguration, and sialorrhea that can reduce the patient's social life and create shame and embarrassment: A psychological intake, in addition to the usefulness to the patient, can also provide current support to caregivers and family members. Therefore clinicians must define a personalized pathway for patients, considering the characteristics of the disease and the type of treatment proposed, to optimize health status and prevent possible side effects while also improving QoL and treatment adherence.
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Quimioradioterapia , Neoplasias de Cabeza y Cuello , Calidad de Vida , Carcinoma de Células Escamosas de Cabeza y Cuello , Humanos , Quimioradioterapia/métodos , Quimioradioterapia/efectos adversos , Neoplasias de Cabeza y Cuello/terapia , Carcinoma de Células Escamosas de Cabeza y Cuello/terapia , Ejercicio Preoperatorio , Carcinoma de Células Escamosas/terapiaAsunto(s)
Anticuerpos Monoclonales , Carcinoma de Pulmón de Células no Pequeñas , Quimioradioterapia , Análisis Costo-Beneficio , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/economía , Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Carcinoma de Pulmón de Células no Pequeñas/terapia , Anticuerpos Monoclonales/economía , Anticuerpos Monoclonales/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/economía , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/patología , Quimioradioterapia/economía , Quimioradioterapia/métodos , Estadificación de Neoplasias , Antineoplásicos Inmunológicos/economía , Antineoplásicos Inmunológicos/uso terapéutico , Nivel de Atención/economíaRESUMEN
Background: Although chemoradiotherapy is an effective treatment for esophageal cancer, its feasibility in esophageal cancer with cirrhosis remains largely unclear. Methods: We retrospectively studied 11 patients with superficial esophageal cancer with liver cirrhosis (Child-Pugh score ≤8) who underwent radical chemoradiotherapy from four centers, and the overall survival rate, local control rate and adverse events at 1 and 3 years were explored. Results: The median age of the included patients was 67 years (Inter-Quartile Range 60-75 years). Complete response was observed in most patients (n = 10, 90.9%), and the remaining patient was unevaluable. The 1- and 3-year overall survival and local control rates were 90.9% and 90.9%, and 72.7% and 63.6%, respectively. Hematotoxicity was a common adverse reaction, and seven patients developed radiation esophagitis, with grade 3-4 observed in two cases. All cases of radiation dermatitis (n = 4) and radiation pneumonia (n = 2) were grade 1-2. Gastrointestinal bleeding occurred in two patients, including one with grade 1-2 bleeding, and one died. Conclusion: Radical chemoradiotherapy is a potential treatment option for patients with superficial esophageal cancer complicated with cirrhosis. However, it can increase the risk of bleeding, which warrants prompt recognition and intervention.
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Quimioradioterapia , Neoplasias Esofágicas , Cirrosis Hepática , Humanos , Persona de Mediana Edad , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/mortalidad , Neoplasias Esofágicas/complicaciones , Masculino , Anciano , Cirrosis Hepática/complicaciones , Cirrosis Hepática/mortalidad , Femenino , Estudios Retrospectivos , Quimioradioterapia/efectos adversos , Quimioradioterapia/métodos , Resultado del TratamientoRESUMEN
BACKGROUND: Stromal fibrosis is highly associated with therapeutic resistance and poor survival in esophageal squamous cell carcinoma (ESCC) patients. Low expression of plasma gelsolin (pGSN), a serum abundant protein, has been found to correlate with inflammation and fibrosis. Here, we evaluated pGSN expression in patients with different stages of cancer and therapeutic responses, and delineated the molecular mechanisms involved to gain insight into therapeutic strategies for ESCC. METHODS: Circulating pGSN level in ESCC patients was determined by enzyme-linked immunosorbent assay analysis, and the tissue microarray of tumors was analyzed by immunohistochemistry staining. Cell-based studies were performed to investigate cancer behaviors and molecular mechanisms, and mouse models were used to examine the pGSN-induced tumor suppressive effects in vivo. RESULTS: Circulating pGSN expression is distinctively decreased during ESCC progression, and low pGSN expression correlates with poor therapeutic responses and poor survival. Methylation-specific PCR analysis confirmed that decreased pGSN expression is partly attributed to the hypermethylation of the GSN promoter, the gene encoding pGSN. Importantly, cell-based immunoprecipitation and protein stability assays demonstrated that pGSN competes with oncogenic tenascin-C (TNC) for the binding and degradation of integrin αvß3, revealing that decreased pGSN expression leads to the promotion of oncogenic signaling transduction in cancer cells and fibroblasts. Furthermore, overexpression of pGSN caused the attenuation of TNC expression and inactivation of cancer-associated fibroblast (CAF), thereby leading to tumor growth inhibition in mice. CONCLUSIONS: Our results demonstrated that GSN methylation causes decreased secretion of pGSN, leading to integrin dysregulation, oncogenic TNC activation, and CAF formation. These findings highlight the role of pGSN in therapeutic resistance and the fibrotic tumor microenvironment of ESCC.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Gelsolina , Microambiente Tumoral , Humanos , Carcinoma de Células Escamosas de Esófago/metabolismo , Gelsolina/genética , Gelsolina/metabolismo , Ratones , Neoplasias Esofágicas/metabolismo , Animales , Masculino , Femenino , Quimioradioterapia/métodos , Persona de Mediana Edad , Línea Celular Tumoral , Resistencia a Antineoplásicos , FibrosisRESUMEN
OBJECTIVE: To explore the survival effect of thoracic gross tumor volume (GTV) in three-dimensional (3D) radiotherapy for stage IV non-small cell lung cancer (NSCLC). METHODS: The data cases were obtained from a single-center retrospective analysis. From May. From 2008 to August 2018, 377 treatment criteria were enrolled. GTV was defined as the volume of the primary lesion and the hilus as well as the mediastinal metastatic lymph node. Chemotherapy was a platinum-based combined regimen of two drugs. The number of median chemotherapy cycles was 4 (2-6), and the cut-off value of the planning target volume (PTV) dose of the primary tumor was 63 Gy (30-76.5 Gy). The cut-off value of GTV volume was 150 cm3 (5.83-3535.20 cm3). RESULTS: The survival rate of patients with GTV <150 cm3 is better than patients with GTV ≥150 cm3. Multivariate Cox regression analyses suggested that peripheral lung cancer, radiation dose ≥63 Gy, GTV <150 cm3, 4-6 cycles of chemotherapy, and CR + PR are good prognostic factors for patients with stage IV non-small cell lung cancer. The survival rate of patients with GTV <150 cm3 was longer than patients with ≥150 cm3 when they underwent 2 to 3 cycles of chemotherapy concurrent 3D radiotherapy (p < 0.05). When performing 4 to 6 cycles of chemotherapy concurrent 3D radiotherapy, there was no significant difference between <150 cm3 and ≥150 cm3. CONCLUSIONS: The volume of stage IV NSCLC primary tumor can affect the survival of patients. Appropriate treatment methods can be opted by considering the volume of tumors to extend patients' lifetime to the utmost.
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Carcinoma de Pulmón de Células no Pequeñas , Quimioradioterapia , Neoplasias Pulmonares , Estadificación de Neoplasias , Carga Tumoral , Humanos , Carcinoma de Pulmón de Células no Pequeñas/terapia , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/tratamiento farmacológico , Masculino , Femenino , Quimioradioterapia/métodos , Persona de Mediana Edad , Anciano , Estudios Retrospectivos , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Anciano de 80 o más Años , Pronóstico , Tasa de SupervivenciaRESUMEN
PURPOSE: To evaluate the long-term efficacy and safety of GP and TPF sequential chemotherapy regimens in patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC). METHODS: From 2005 to 2016, a total of 408 LA-NPC patients treated with GP or TPF sequential chemoradiotherapy were retrospectively included. Propensity Score Matching (PSM) was employed to balance the baseline variables. Survival outcomes and acute toxicities were compared between both groups. RESULTS: A total of 230 patients were selected by 1:1 PSM. At a median follow-up of 91 months, no significant differences were observed between the matched GP and TPF groups regarding 5-year overall survival, progression-free survival, distant metastasis-free survival, and locoregionally relapse-free survival (83.4% vs. 83.4%, P = 0.796; 75.6% vs. 68.6%, P = 0.301; 86.7% vs. 81.1%, P = 0.096; and 87.4% vs. 87.2%, P = 0.721). Notable disparities in adverse effects were identified, with higher incidences of grade 3/4 thrombocytopenia in the GP group while grade 3/4 leukopenia and neutropenia in the TPF group. Though not recorded in our cohort, combined with the FAERS database, thrombotic adverse reactions are a concern for the GP regimen, while the TPF regimen requires vigilance for life-threatening adverse reactions such as septic shock, acute respiratory distress syndrome, and laryngeal edema. CONCLUSION: No significant difference in long-term outcomes was observed between the GP and TPF sequential chemotherapy regimens for LA-NPC. Differences in adverse effects should be noted when choosing the regimen.
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Protocolos de Quimioterapia Combinada Antineoplásica , Quimioradioterapia , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Puntaje de Propensión , Humanos , Masculino , Femenino , Carcinoma Nasofaríngeo/terapia , Carcinoma Nasofaríngeo/patología , Carcinoma Nasofaríngeo/mortalidad , Carcinoma Nasofaríngeo/tratamiento farmacológico , Persona de Mediana Edad , Quimioradioterapia/efectos adversos , Quimioradioterapia/métodos , Neoplasias Nasofaríngeas/terapia , Neoplasias Nasofaríngeas/patología , Neoplasias Nasofaríngeas/tratamiento farmacológico , Neoplasias Nasofaríngeas/mortalidad , Estudios Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Adulto , Anciano , Resultado del Tratamiento , Cisplatino/administración & dosificación , Cisplatino/uso terapéutico , Cisplatino/efectos adversos , Fluorouracilo/administración & dosificación , Fluorouracilo/efectos adversos , Fluorouracilo/uso terapéutico , Gemcitabina , Estudios de Seguimiento , Compuestos OrganoplatinosRESUMEN
Combination of immunotherapy with radiotherapy is under active investigation. The PACIFIC trial firmly established the treatment paradigm of consolidation immunotherapy following definitive chemoradiotherapy, inspiring a series of similar or exploratory combination regimens. This summary highlighted six reports updated in the 2024 ASCO Annual Meeting.
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Inmunoterapia , Neoplasias , Humanos , Inmunoterapia/métodos , Neoplasias/terapia , Neoplasias/inmunología , Neoplasias/radioterapia , Quimioradioterapia/métodos , Terapia Combinada , Oncología Médica/métodos , Oncología Médica/tendencias , Sociedades MédicasRESUMEN
Importance: Patients with locally advanced rectal cancer and persistent lymph node metastases (PLNM) after neoadjuvant treatment are at high risk of developing locoregional and distant metastasis, yet optimal postsurgical treatment of these patients is limited. Objective: To analyze the association of PLNM with pretreatment clinical parameters, intensity of neoadjuvant treatment, and long-term oncological outcomes. Design, Setting, and Participants: This cohort study is a post-hoc analysis of 3 randomized clinical trials (Surgical Oncology Working Group of Germany [CAO], Radiological Oncology Working Group of Germany [ARO], and Working Group for Internal Oncology in the German Cancer Society [AIO]) conducted in Germany in 1994, 2004, and 2012 that included 1948 patients with locally advanced rectal cancer recruited between February 1995 and January 2018. Statistical analysis was conducted between September 2023 and February 2024. Exposures: Receiving preoperative fluorouracil-based chemoradiotherapy (CRT, comprising the preoperative group of CAO/ARO/AIO-94 and the control group of CAO/ARO/AIO-04), fluorouracil-based CRT plus oxaliplatin (experimental group of CAO/ARO/AIO-04), or total neoadjuvant treatment (TNT) with fluorouracil-based CRT plus oxaliplatin with induction or consolidation leucovorin calcium (folinic acid), fluorouracil, and oxaliplatin chemotherapy within the CAO/ARO/AIO-12 trial. Main Outcome and Measures: The associations of PLNM with clinical parameters, intensity of neoadjuvant treatment, and cumulative incidences of LR, DM, and overall survival were assessed. Results: A total of 1888 patients (1333 male participants [70.6%]; median [range] age, 62 [19-84] years) with locally advanced rectal adenocarcinoma (clinical tumor stage 3 to 4 and/or clinically node-positive) treated within 3 consecutive clinical trials were analyzed. A total of 522 (29%) experienced PLNM; 378 had lymph node stage (ypN) 1 (20%) after neoadjuvant treatment (ypN) 1 (20%), and 174 had ypN2 (9%). Age, clinical T-stage, N-stage, grading, carcinoembryonic antigen levels, and time interval from completion of CRT to surgery were significantly associated with PLNM, whereas sex and tumor location were not. The percentage of patients with ypN2 stage was almost halved after TNT (18 of 293 patients [6%]) compared with patients treated with fluorouracil-based CRT (114 of 1009 patients [11.3%]; χ26 = 16.693; P = .01). After a median (IQR) follow-up of 54 (37-62) months, 5-year overall survival was 86.1% (95% CI, 83.9%-88.4%) for ypN0, 74.0% (95% CI, 83.9%-88.4%) for ypN1, and 43% for ypN2 (95% CI, 35.4%-52.2%) (P < .001). The 5-year cumulative incidences of locoregional and distant metastases were, respectively, 3% (95% CI, 2.1%-4.2%) and 20% (95% CI, 18%-23%) for ypN0, 6% (95% CI, 3.4%-8.8%) and 40% (95% CI, 34%-46%) for ypN1, and 19% (95% CI, 13%-26%) and 72% (95% CI, 63%-79%) for ypN2 (both P < .001). Conclusions and Relevance: In this cohort study, PLNM unmasked an unfavorable phenotype of rectal cancer at high risk for treatment failure. More aggressive adjuvant treatment might be considered; however, risk-adapted surveillance strategies and early recurrence-directed surgery, if feasible, are important strategies in this group of patients with CRT- and/or chemotherapy-resistant disease.
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Metástasis Linfática , Terapia Neoadyuvante , Neoplasias del Recto , Humanos , Neoplasias del Recto/patología , Neoplasias del Recto/terapia , Masculino , Femenino , Terapia Neoadyuvante/métodos , Persona de Mediana Edad , Anciano , Adulto , Estudios de Cohortes , Alemania/epidemiología , Quimioradioterapia/métodos , Fluorouracilo/uso terapéutico , Fluorouracilo/administración & dosificaciónRESUMEN
BACKGROUND AND OBJECTIVE: To investigate the oncologic outcomes of patients with esophageal squamous cell carcinoma (ESCC) who have achieved a pathologic complete response (pCR) of the primary tumor (ypT0) after neoadjuvant chemoradiotherapy (NCRT). METHODS: Patients with thoracic ESCC who underwent scheduled NCRT followed by surgery at our hospital between January 2010 and December 2022 were retrospectively analyzed. Only patients with ypT0 disease were enrolled in this study. RESULTS: A total of 118 patients were ultimately enrolled in this study. Ninety-two patients achieved pCR in the primary tumor and lymph nodes (ypT0N0), while 26 patients had residual metastatic disease in 52 lymph nodes (ypT0N+). Forty-five of the 52 lymph nodes with residual tumors were abdominal lymph nodes. Positive lymph nodes were more often observed in patients with tumors located in the lower third of the esophagus. The 1-, 3-, and 5-year overall survival (OS) rates for the entire study group were 96.5%, 79.5%, and 77.1%, and the 1-, 3-, and 5-year disease-free survival (DFS) rates were 90.5%, 76.8%, and 69.0%, respectively. According to multivariate analyses, pN classification was an independent predictor of both OS and DFS (P < 0.05), while sex and cT classification were also found to be independent prognostic factors for DFS (P < 0.05). CONCLUSIONS: Residual nodal metastatic disease in patients with ypT0 ESCC after NCRT was more often found in the abdominal lymph nodes. pN classification was an independent predictor of both OS and DFS for ypT0 ESCC patients after NCRT.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Terapia Neoadyuvante , Humanos , Masculino , Femenino , Persona de Mediana Edad , Terapia Neoadyuvante/métodos , Carcinoma de Células Escamosas de Esófago/terapia , Carcinoma de Células Escamosas de Esófago/patología , Carcinoma de Células Escamosas de Esófago/mortalidad , Estudios Retrospectivos , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/mortalidad , Anciano , Quimioradioterapia/métodos , Adulto , Resultado del Tratamiento , Metástasis Linfática , Estadificación de Neoplasias , Supervivencia sin Enfermedad , Esofagectomía , Tasa de SupervivenciaRESUMEN
BACKGROUND: Neoadjuvant chemoradiotherapy (nCRT) followed by surgery remains a standard of care for resectable esophageal cancer (EC), and definitive chemoradiotherapy (dCRT) is an alternative for unresectable diseases. However, it is controversial for the use of the two aggressive regimens in elderly patients. METHODS: We systematically searched multiple databases for studies comparing overall survival (OS) and/or progression-free survival (PFS) between dCRT and surgery (nCRT + surgery or surgery alone) or between dCRT and radiotherapy (RT) alone in elderly patients (age ≥ 65 years) until March 28, 2024. Statistical analysis was performed using random-effects model. RESULTS: Fourty-five studies with 33,729 patients were included. dCRT significantly prolonged OS (hazard ratio [HR] = 0.64, 95% confidence interval [CI]: 0.58-0.70) and PFS (HR = 0.67, 95% CI: 0.60-0.76) compared to RT alone for unresectable EC, and resulted in a worse OS compared to surgery for resectable cases (HR = 1.34, 95% CI: 1.23-1.45). Similar results of OS were also observed when the multivariate-adjusted HRs were used as the measure of effect (dCRT vs. RT alone: HR = 0.65, 95% CI: 0.58-0.73; dCRT vs. surgery: HR = 1.49, 95% CI: 1.28-1.74). Subgroup analyses according to age group (≥ 70, ≥ 75, or ≥ 80 years), study design, study region, histological type, radiation field, chemotherapy regimen revealed comparable results. CONCLUSIONS: nCRT + surgery is likely a preferred strategy for elderly patients with good physiological conditions; and dCRT is a better alternative for unresectable cases. Advanced age alone does not appear to be a key predictor for the tolerability of the two aggressive treatments.
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Neoplasias Esofágicas , Terapia Neoadyuvante , Humanos , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/mortalidad , Neoplasias Esofágicas/patología , Anciano , Terapia Neoadyuvante/métodos , Quimioradioterapia/métodos , Anciano de 80 o más Años , Esofagectomía , MasculinoRESUMEN
Objectives. This study investigates the association between cerebral blood flow (CBF) and overall survival (OS) in glioblastoma multiforme (GBM) patients receiving chemoradiation. Identifying CBF biomarkers could help predict patient response to this treatment, facilitating the development of personalized therapeutic strategies.Materials and Methods. This retrospective study analyzed CBF data from dynamic susceptibility contrast (DSC) MRI in 30 newly diagnosed GBM patients (WHO grade IV). Radiomics features were extracted from CBF maps, tested for robustness, and correlated with OS. Kaplan-Meier analysis was used to assess the predictive value of radiomic features significantly associated with OS, aiming to stratify patients into groups with distinct post-treatment survival outcomes.Results. While mean relative CBF and CBV failed to serve as independent prognostic markers for OS, the prognostic potential of radiomic features extracted from CBF maps was explored. Ten out of forty-three radiomic features with highest intraclass correlation coefficients (ICC > 0.9), were selected for characterization. While Correlation and Zone Size Variance (ZSV) features showed significant OS correlations, indicating prognostic potential, Kaplan-Meier analysis did not significantly stratify patients based on these features. Visual analysis of the graphs revealed a predominant association between the identified radiomic features and OS under two years. Focusing on this subgroup, Correlation, ZSV, and Gray-Level Nonuniformity (GLN) emerged as significant, suggesting that a lack of heterogeneity in perfusion patterns may be indicative of a poorer outcome. Kaplan-Meier analysis effectively stratified this cohort based on the features mentioned above. Receiver operating characteristic (ROC) analysis further validated their prognostic value, with ZSV demonstrating the highest sensitivity and specificity (0.75 and 0.85, respectively).Conclusion. Our findings underscored radiomics features sensitive to CBF heterogeneity as pivotal predictors for patient stratification. Our results suggest that these markers may have the potential to identify patients who are unlikely to benefit from standard chemoradiation therapy.
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Neoplasias Encefálicas , Circulación Cerebrovascular , Glioblastoma , Imagen por Resonancia Magnética , Humanos , Glioblastoma/diagnóstico por imagen , Glioblastoma/patología , Pronóstico , Masculino , Femenino , Persona de Mediana Edad , Neoplasias Encefálicas/diagnóstico por imagen , Estudios Retrospectivos , Imagen por Resonancia Magnética/métodos , Anciano , Adulto , Estimación de Kaplan-Meier , Quimioradioterapia/métodos , RadiómicaRESUMEN
INTRODUCTION: Cervical cancer, while highly preventable, remains an international public health challenge especially in under resourced regions. Although early-stage cervix confined cancers are often amenable to surgical resection, larger tumors deemed locally advanced cervical cancer (LACC) necessitate systemic therapy as part of chemoradiation therapy. Moreover, systemic therapy is the standard therapeutic approach for those presenting with primary metastasis or recurrence. AREAS COVERED: While several agents have been approved to treat recurrent cervical cancer including checkpoint inhibitors as well as both biomarker agnostic and specific antibody drug conjugates, the development of agents added to chemoradiation has been less fruitful. Until recently, the addition of novel therapies to chemoradiation has been negative in terms of improving outcomes; however, results of a recent Phase III clinical trial (NCT04221945) in LACC demonstrated that the addition of pembrolizumab to standard of care chemoradiation was associated with an improvement in progression-free survival and resulted in an FDA approval for this therapy. This observation led to the first change in treating LACC since the early 2000s. EXPERT OPINION: Improvements in systemic therapy both alone and in combination with chemoradiation for cervical cancer have been realized. Ongoing research is needed for therapeutic options following immunotherapy.
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Quimioradioterapia , Recurrencia Local de Neoplasia , Nivel de Atención , Neoplasias del Cuello Uterino , Humanos , Neoplasias del Cuello Uterino/tratamiento farmacológico , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/terapia , Femenino , Quimioradioterapia/métodos , Recurrencia Local de Neoplasia/tratamiento farmacológico , Supervivencia sin Progresión , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inmunoterapia/métodos , Estadificación de Neoplasias , Antineoplásicos/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéuticoRESUMEN
PURPOSE: For women with locoregionally advanced cervical cancer, the standard of care treatment is the curatively intended chemoradiation therapy (CRT). A relationship between bone marrow (BM) dose-volume histograms (DVHs) and acute hematological toxicity (HT) has been debated recently. Aim of this study was the evaluation of BM dose constraints and HT in a contemporary patient cohort. METHODS: Radiation treatment plans of 31 patients with cervical cancer (FIGO stage IIB-IVB) treated with intensity-modulated radiotherapy and simultaneous chemotherapy were explored retrospective. Pelvic bones (PB) and femoral heads (FH) were contoured and DVHs were correlated with white blood cells (WBC), hemoglobin levels and platelets. RESULTS: Comparing the absolute blood levels with the dose volumes of both FH and PB the data showed a significant correlation between WBC and the median dose of the FH and the median dose, V30Gy, V40Gy and V50Gy of the PB. A correlation between the toxicity grade of anemia and mean dose, maximum dose and V5Gy of the PB was found. Counting the highest grade of HT of all three blood levels of each patient, significant correlations were found for the mean and median dose, V30Gy, V40Gy and V50Gy of the PB. CONCLUSION: The results show that blood levels may correlate with distinct dosimetric subvolumes of critical bone marrow compartments with a potential impact on therapeutic outcome and treatment-related toxicity. The data presented are in line with the previous findings on the relevance of dosimetric exposure of pelvic bony subvolumes.
Asunto(s)
Médula Ósea , Radioterapia de Intensidad Modulada , Neoplasias del Cuello Uterino , Humanos , Femenino , Neoplasias del Cuello Uterino/radioterapia , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/terapia , Radioterapia de Intensidad Modulada/efectos adversos , Radioterapia de Intensidad Modulada/métodos , Médula Ósea/efectos de la radiación , Médula Ósea/efectos de los fármacos , Médula Ósea/patología , Persona de Mediana Edad , Adulto , Dosificación Radioterapéutica , Anciano , Estudios Retrospectivos , Quimioradioterapia/efectos adversos , Quimioradioterapia/métodos , Planificación de la Radioterapia Asistida por Computador/métodos , Terapia CombinadaRESUMEN
The objective of this study was to construct a concise prediction model for serious adverse events (SAEs) in order to assess the likelihood of SAE occurrence among hospitalized patients undergoing concurrent chemoradiotherapy. An electronic database of a Cancer Centre was utilized to conduct a cross-sectional review survey. Our research involved the recruitment of 239 patients who were undergoing concurrent chemoradiotherapy in the Department of Nasopharynx and Radiotherapy. The clinical prediction rule was derived using logistic regression analysis, with SAE serving as the primary outcome. Internal verification was conducted. The occurrence rate of SAE in the derivation cohort was 59.4%. The ultimate model used had 3 variables, namely cystatin C, C-reactive protein, and serum amyloid A. The model exhibited an area under the curve of 0.626 (95% CI: 0.555-0.696; Pâ <â .001). The model accurately predicts the occurrence of SAE, and the variable data can be easily obtained, and the assessment technique is straightforward.
Asunto(s)
Quimioradioterapia , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Humanos , Masculino , Carcinoma Nasofaríngeo/terapia , Femenino , Quimioradioterapia/efectos adversos , Quimioradioterapia/métodos , Persona de Mediana Edad , Neoplasias Nasofaríngeas/terapia , Estudios Transversales , Adulto , Medición de Riesgo , Anciano , Modelos Logísticos , Estudios Retrospectivos , Proteína C-Reactiva/análisisRESUMEN
BACKGROUND AND AIM: The German NPC-GPOH trials introduced treatment including neoadjuvant chemotherapy, radiochemotherapy (RCT) and antiviral treatment in patients aged 25 years or younger with nasopharyngeal cancer (NPC). We conducted a retrospective study on outcomes of patients at the age of ≥26 years treated accordingly at our institution. METHODS: Consecutive patients who received primary RCT for NPC were included. The Kaplan-Meier method was used to calculate survival probabilities, and the Cox regression analysis was used to test for an influence of the variables on outcomes. Acute and late toxicity were evaluated via CTCAE criteria and LENT/SOMA criteria, respectively. RESULTS: In total, 30 patients were included. Diagnosis was made from 09/1994 to 11/2016. The median 5 year overall survival (OS), disease-free survival (DFS), cancer-specific survival (CSS) and locoregional recurrence-free survival (LRC) were 75%, 56%, 83%, and 85%, respectively. We found a negative impact on outcomes (p < .05) in case of older age (OS), history of smoking (OS), and T4 stage/ UICC stage IV (DFS). WHO histologic type significantly influenced outcomes, with best outcomes for type III and worst outcomes for type I. The rates of acute and late toxicities were acceptable. CONCLUSION: We found excellent outcomes and good feasibility of the NPC-GPOH trials regimen in adult patients. Additionally, we identified patients with outcomes which need to be improved (smokers, histologic type I tumors) and with particularly excellent outcomes (histologic type III tumors). This stimulates further studies on treatment intensification or de-escalation aiming at reduced side effects with optimal tumor control in NPC.
Asunto(s)
Quimioradioterapia , Neoplasias Nasofaríngeas , Terapia Neoadyuvante , Humanos , Masculino , Femenino , Neoplasias Nasofaríngeas/terapia , Neoplasias Nasofaríngeas/mortalidad , Neoplasias Nasofaríngeas/patología , Adulto , Estudios Retrospectivos , Persona de Mediana Edad , Quimioradioterapia/métodos , Terapia Neoadyuvante/métodos , Adulto Joven , Carcinoma Nasofaríngeo/terapia , Carcinoma Nasofaríngeo/mortalidad , Carcinoma Nasofaríngeo/patología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Estadificación de Neoplasias , Anciano , Antivirales/uso terapéutico , Antivirales/administración & dosificación , Supervivencia sin Enfermedad , Terapia Combinada/métodos , Tasa de SupervivenciaRESUMEN
Male infertility is a recognized side effect of chemoradiotherapy. Extant spermatogonial stem cells (SSCs) may act as originators for any subsequent recovery. However, which type of SSCs, the mechanism by which they survive and resist toxicity, and how they act to restart spermatogenesis remain largely unknown. Here, we identify a small population of Set domain-containing protein 4 (Setd4)-expressing SSCs that occur in a relatively dormant state in the mouse seminiferous tubule. Extant beyond high-dose chemoradiotherapy, these cells then activate to recover spermatogenesis. Recovery fails when Setd4+ SSCs are deleted. Confirmed to be of fetal origin, these Setd4+ SSCs are shown to facilitate early testicular development and also contribute to steady-state spermatogenesis in adulthood. Upon activation, chromatin remodeling increases their genome-wide accessibility, enabling Notch1 and Aurora activation with corresponding silencing of p21 and p53. Here, Setd4+ SSCs are presented as the originators of both testicular development and spermatogenesis recovery in chemoradiotherapy-induced infertility.
Asunto(s)
Infertilidad Masculina , Espermatogénesis , Masculino , Animales , Espermatogénesis/efectos de los fármacos , Espermatogénesis/efectos de la radiación , Infertilidad Masculina/terapia , Ratones , Quimioradioterapia/efectos adversos , Quimioradioterapia/métodos , Células Madre/metabolismo , Células Madre/efectos de la radiación , Ratones Endogámicos C57BL , Proteína p53 Supresora de Tumor/metabolismo , Proteína p53 Supresora de Tumor/genética , Ensamble y Desensamble de Cromatina/efectos de los fármacos , Testículo/efectos de los fármacos , Testículo/metabolismo , Receptor Notch1/metabolismo , Receptor Notch1/genéticaRESUMEN
Purpose: 68Ga-labeled fibroblast activation protein inhibitor (FAPI) is a novel PET tracer with great potential for staging pancreatic cancer. Data on locally advanced or recurrent disease is sparse, especially on tracer uptake before and after high dose chemoradiotherapy (CRT). The aim of this study was to evaluate [68Ga]Ga-FAPI-46 PET/CT staging in this setting. Methods: Twenty-seven patients with locally recurrent or locally advanced pancreatic adenocarcinoma (LRPAC n = 15, LAPAC n = 12) in stable disease or partial remission after chemotherapy underwent FAPI PET/CT and received consolidation CRT in stage M0 with follow-up FAPI PET/CT every three months until systemic progression. Quantitative PET parameters SUVmax, SUVmean, FAPI-derived tumor volume and total lesion FAPI-uptake were measured in baseline and follow-up PET/CT scans. Contrast-enhanced CT (ceCT) and PET/CT data were evaluated blinded and staged according to TNM classification. Results: FAPI PET/CT modified staging compared to ceCT alone in 23 of 27 patients in baseline, resulting in major treatment alterations in 52% of all patients (30%: target volume adjustment due to N downstaging, 15%: switch to palliative systemic chemotherapy only due to diffuse metastases, 7%: abortion of radiotherapy due to other reasons). Regarding follow-up scans, major treatment alterations after performing FAPI PET/CT were noted in eleven of 24 follow-up scans (46%) with switch to systemic chemotherapy or best supportive care due to M upstaging and ablative radiotherapy of distant lymph node and oligometastasis. Unexpectedly, in more than 90 % of the follow-up scans, radiotherapy did not induce local fibrosis related FAPI uptake. During the first follow-up, all quantitative PET metrics decreased, and irradiated lesions showed significantly lower FAPI uptake in locally controlled disease (SUVmax p = 0.047, SUVmean p = 0.0092) compared to local failure. Conclusion: Compared to ceCT, FAPI PET/CT led to major therapeutic alterations in patients with LRPAC and LAPAC prior to and after radiotherapy, which might help identify patients benefiting from adjustments in every treatment stage. FAPI PET/CT should be considered a useful diagnostic tool in LRPAC or LAPAC before and after CRT.