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Antecedentes: La radioquimioterapia neoadyuvante es uno de los pilares del tratamiento del cáncer de recto localmente avanzado. La neoadyuvancia ha demostrado disminuir la recidiva local, generando también un downstaging tumoral, llegando incluso a una respuesta patológica completa (RPC), esta última relacionada con una mejor sobrevida global (SG) y sobrevida libre de enfermedad (SLE). Objetivo: Reportar los resultados anátomo-patológicos del tratamiento con radioquimioterapia en cáncer de recto, analizando su relación con la SG y la SLE. Material y Método: Estudio de cohorte prospectivo. Se analiza base de datos de cirugías coloproctológicas del Hospital Clínico de la Universidad de Chile, entre los años 20042019, incluyendo pacientes con cáncer de recto medio y bajo localmente avanzados, los cuales recibieron neoadyuvancia y posteriormente cirugía. Se realizó el análisis de sobrevida con el método de Kaplan-Meier y el test Log-rank para su comparación. Se consideró estadísticamente significativo un valor de p < 0,05. Resultados: 411 pacientes fueron operados por cáncer de recto, 143 pacientes recibieron neoadyuvancia, el 19% registró RPC. La SG del grupo con RPC fue 94% (IC 95%; 59,79-79,41%) mientras que la del grupo sin RPC fue 71% (IC 95%; 66,64-99,20%) (p = 0,018), la SLE en aquellos pacientes con RPC alcanzó un 100%, mientras que en aquellos sin RPC fue 74% (IC 95%; 64,08-81,28) (p = 0,008). Conclusiones: Los pacientes con RPC mostraron mejores resultados a largo plazo que aquellos sin RPC. La RPC podría indicar un perfil tumoral biológico favorable, con menos tendencia a la recurrencia y mejor supervivencia.
Background: One of the mainstays in the treatment of locally advanced rectal cancer is neoadjuvant chemoradiotherapy. Neoadjuvant therapy have demonstrated to decrease local recurrence, also generating tumor downstaging, even leading to a pathological complete response (PCR), the latter related to better overall survival (OS) and disease-free survival (SLE). Aim: To report the anatomo-pathological results of treatment with chemoradiotherapy in rectal cancer, analyzing the relationship with OS and SLE. Material and Method: Prospective cohort study. A database of colorectal surgeries from the Clinical Hospital of the University of Chile between the years 2004-2019, including patients with locally advanced low and middle rectal cancer, who received neoadjuvant and later surgery. Survival analysis was made with the Kaplan-Meier method and the Log-rank test for comparison. A value of p < 0.05 was considered statistically significant. Results: 411 patients underwent surgery for rectal cancer, 143 patients received neoadjuvant therapy, 19% registered PCR. The OS of the group with PCR was 94% (95% CI; 59.79-79.41%) while that of the group without PCR was 71% (95% CI; 66.64-99.20%) (p = 0.018), the SLE in those patients with PCR reached 100%, while in those without PCR it was 74% (95% CI; 64.08-81.28) (p = 0.008). Conclusions: Patients with PCR have better long-term results than those without PCR. PCR could indicate a favorable biological tumor profile, with less tendency to recurrence and improved survival.
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Abstract Objective To evaluate the efficacy and safety of Alternating Chemoradiotherapy (ACRT) using cisplatin and 5-Fluorouracil (5-FU) in patients with nasopharyngeal carcinoma. Methods This was a retrospective study in which patients' clinical records were reviewed to identify patients with a new diagnosis of nasopharyngeal carcinoma at our institution between January 2005 and January 2019. Thirty-seven eligible patients were identified; of these, the clinical details of 27 patients treated with ACRT were evaluated. Patient outcomes, including overall survival and progression-free survival, and adverse events were assessed. Results Of these initial 37 patients, 1, 10, 13, 10, and 3 were staged as I, II, III, IVA, and IVB, respectively, as defined by the 8th edition of the TNM classification system. Twenty-seven patients received ACRT comprising sequential administration of chemotherapy, radiotherapy (wide field), chemotherapy, radiotherapy (shrinking field), and chemotherapy. The 5-year overall survival and progression-free survival rates were 83.7% and 88.9%, respectively. Treatment compliance was 93%, which is comparable to that of previous reports. Conclusion ACRT using cisplating and 5-fluorouracil was well tolerated with acceptable efficacy. Level of Evidence IVa
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Abstract Objective Extended curettage with adjuvants of giant cell tumors of bone is associated with a lower rate of recurrence of the tumor while preserving the adjacent joint. The present study was conducted to estimate the recurrence rate and functional outcome after using argon beam as an adjuvant for extended curettage. Methods We selected 50 patients with giant cell tumors, meeting all the inclusion criteria, who underwent extended curettage using high speed burr and argon beam photocoagulation between July 2016 to January 2019. On their follow-up visit, they were assessed for any complaints of pain and signs like tenderness, locally raised temperature, and decreased range of motion of the adjacent joint. Radiologically, the patients were assessed for any increased lucency around the cement mantle and uptake of the subarticular graft. Musculoskeletal Tumor Society Score (MSTS) was administered to the patients, and range of motion of the adjacent joint was compared with the contralateral joint. Results Recurrence was found in 4 patients, that is, an 8% recurrence rate. Twenty-six out of 28 patients with a tumor in the lower limb had a grade-5 weight bearing status 6 months from the surgery, and their range of motion was comparable to contralateral healthy joint with an average MSTS score of 27 (18-30). Conclusion Extended curettage of giant cell tumors using argon beam coagulation is associated with low recurrence rates of the tumor and is an effective modality in the treatment of these tumors besides having a functional outcome comparable to the healthy limb.
Resumo Objetivo A curetagem estendida com adjuvantes de tumores de células gigantes do osso está associada a uma menor taxa de recidiva da neoplasia e à preservação da articulação adjacente. Este estudo foi feito para estimar a taxa de recidiva e o resultado funcional após o uso de plasma de argônio como adjuvante à curetagem estendida. Métodos Cinquenta pacientes com tumores de células gigantes que atendiam a todos os critérios de inclusão foram selecionados para o estudo e submetidos à curetagem estendida com broca de alta velocidade e fotocoagulação com plasma de argônio entre julho de 2016 e janeiro de 2019. À consulta de acompanhamento, os pacientes foram avaliados quanto a quaisquer queixas de dor e sinais como sensibilidade, aumento local da temperatura e diminuição da amplitude de movimento da articulação adjacente. Radiologicamente, os pacientes foram avaliados quanto à presença de qualquer aumento de radiotransparência ao redor do manto de cimento e incorporação do enxerto subarticular. O questionário Musculoskeletal Tumor Society Score (MSTS) foi administrado aos pacientes e a amplitude de movimentação da articulação adjacente foi comparada à articulação contralateral. Resultados Quatro pacientes apresentaram recidiva, o que corresponde a uma taxa de 8%. Seis meses após a cirurgia, 26 de 28 pacientes com tumor no membro inferior tinham capacidade de sustentação de peso de grau 5 e amplitude de movimento comparável à articulação saudável contralateral, com pontuação MSTS média de 27 (intervalo de 18 a 30). Conclusão A curetagem estendida de tumores de células gigantes com coagulação por plasma de argônio está associada a baixas taxas de recidiva da neoplasia; é uma modalidade eficaz no tratamento desses tumores e o resultado funcional é comparável ao do membro saudável.
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Humans , Bone Neoplasms/therapy , Giant Cell Tumor of Bone/therapy , Argon Plasma Coagulation , Chemoradiotherapy, AdjuvantABSTRACT
Background: Surgery has been the mainstay treatment for oral cancer. Patients who do not receive surgery are generally treated with concurrent chemoradiotherapy (CCRT). Many factors play a role in patients� survival; tumor volume might be one of those factors. This study aims to determine the effect of the pre-treatment tumor volume on the survival of oral cancer. Methods: Retrospective study of patients with histological confirmed squamous cell carcinoma, stage III朓V oral cancer, who received definitive CCRT. Tumor volume from pre-treatment computed tomography (CT) scans were reviewed and analyzed. The optimal cut-off tumor volume was evaluated by receiver operating characteristic (ROC) curve analysis. Results: Among 67 patients, half of the primary tumor sites were oral tongue. The median total tumor volume (TTV) was 73.25 cm3, while the median survival was 12.5 months (95% confidence interval: 10.9-20.3). The optimal cut-off TTV ?52.9 cm3 (P < 0.0001). The median survival of the patients, who had tumor volume <52.9 cm3 were 34.4 months, and for tumor volume ?52.9 cm3 were 8.6 months (P < 0.0001). Multivariate analysis showed that TTV ?52.9 cm3, and intensity-modulated radiotherapy (IMRT) or volumetric-modulated arc therapy (VMAT) technique had significantly influenced the overall survival. Conclusion: TTV had an influence on the overall survival of locally advanced oral cancer. In addition, TTV may be considered as a factor in selecting the appropriate treatment option for these patients.
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ABSTRACT Metastatic gastric cancer traditionally hinders surgical treatment options, confining them to palliative procedures. The presence of metastases in these tumors is classified as M1, irrespective of their characteristics, quantity, or location. However, oligometastatic disease emerged as an intermediate state between localized and widely disseminated cancer. It exhibits diverse patterns based on metastatic disease extent, type, and location. Adequately addressing this distinctive metastatic state necessitates tailored strategies that surpass the realm of palliative care. Differentprimary tumor types present discernible scenarios of oligometastatic disease, including preferred sites of occurrence and chronological progression. Due to the novelty of this theme and the heterogeneity of the disease, uncertainties still exist, and the ability to provide confident guidelines is challenging. Currently, there are no effective predictors to determine the response and provide clear indications for surgical interventions and systemic treatments in oligometastatic disease. Treatment decisions are commonly based on apparent disease control by systemic therapies, with a short observation period and imaging assessments. Nonetheless, the inherent risk of misinterpretation remains a constant concern. The emergence of novel technologies and therapeutic modalities, such as immunotherapy, cellular therapy, and adoptive therapies, holds the potential to reshape the landscape of surgical treatment for the oligometastatic disease in gastric cancer, expanding the surgeon's role in this multidisciplinary approach. Prospective tools for patient selection in oligometastatic gastric cancer are being explored. Using non-invasive, cost-effective, widely available imaging techniques that provide real-time information may revolutionize medical practice, ensuring precision medicine accessibility, even in resource-constrained small healthcare facilities. Incorporating molecular classifications, liquid biopsies, and radiomic analysis in a complementary protocol will augment patient selection precision for surgical intervention in oligometastasis. Hopefully, these advancements will render surgeries unnecessary in many cases by providing highly effective alternative treatments.
RESUMO O câncer gástrico metastático representa um desafio para o tratamento cirúrgico, restringindo-se a procedimentos paliativos. A presença de metástases nestes tumores é categorizada como estágio M1, independentemente das características, quantidade e localização. No entanto, a doença oligometastática surgiu como um estado intermediário entre o câncer localizado e o amplamente disseminado. A oligometastática apresenta diversos padrões com base na extensão, tipo e localização da doença metastática. Abordar adequadamente esse estado distintivo requer estratégias adaptadas que ultrapassem o escopo dos cuidados paliativos. Diferentes tipos de tumores primários exibem cenários distintos de oligometastática, incluindo locais preferenciais de ocorrência e progressão cronológica. Devido à novidade desse tema e à heterogeneidade da doença, ainda existem incertezas, e a capacidade de fornecer diretrizes seguras é limitada. Atualmente, não existem preditores eficazes para determinar a resposta e fornecer indicações claras para intervenções cirúrgicas e tratamentos sistêmicos em oligometastática. As decisões de tratamento geralmente se baseiam no controle aparente da doença por meio de terapias sistêmicas, com um curto período de observação e avaliação por imagem. No entanto, o risco inerente de interpretação incorreta continua sendo uma preocupação constante. A emergência de novas tecnologias e modalidades terapêuticas, como imunoterapia, terapia celular e terapias adotivas, tem o potencial de remodelar o panorama do tratamento cirúrgico da oligometastática no câncer gástrico, expandindo o papel do cirurgião nessa abordagem multidisciplinar. Ferramentas prospectivas para a seleção de pacientes com câncer gástrico oligometastático estão sendo exploradas. A utilização de técnicas de imagem não invasivas, rentáveis e amplamente disponíveis, que fornecem informações em tempo real, pode revolucionar a prática médica, garantindo a acessibilidade da medicina de precisão, mesmo em unidades de saúde com recursos limitados. A incorporação de classificações moleculares, biópsias líquidas e análises radiômicas em um protocolo complementar aumentará a precisão da seleção de pacientes para intervenção cirúrgica em oligometástases. Espera-se que esses avanços tornem as cirurgias desnecessárias em muitos casos, proporcionando tratamentos alternativos altamente eficazes.
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We conducted a prospective study to assess the non-inferiority of adjuvant chemotherapy alone versus adjuvant concurrent chemoradiotherapy (CCRT) as an alternative strategy for patients with early-stage (FIGO 2009 stage IB-IIA) cervical cancer having risk factors after surgery. The condition was assessed in terms of prognosis, adverse effects, and quality of life. This randomized trial involved nine centers across China. Eligible patients were randomized to receive adjuvant chemotherapy or CCRT after surgery. The primary end-point was progression-free survival (PFS). From December 2012 to December 2014, 337 patients were subjected to randomization. Final analysis included 329 patients, including 165 in the adjuvant chemotherapy group and 164 in the adjuvant CCRT group. The median follow-up was 72.1 months. The three-year PFS rates were both 91.9%, and the five-year OS was 90.6% versus 90.0% in adjuvant chemotherapy and CCRT groups, respectively. No significant differences were observed in the PFS or OS between groups. The adjusted HR for PFS was 0.854 (95% confidence interval 0.415-1.757; P = 0.667) favoring adjuvant chemotherapy, excluding the predefined non-inferiority boundary of 1.9. The chemotherapy group showed a tendency toward good quality of life. In comparison with post-operative adjuvant CCRT, adjuvant chemotherapy treatment showed non-inferior efficacy in patients with early-stage cervical cancer having pathological risk factors. Adjuvant chemotherapy alone is a favorable alternative post-operative treatment.
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Female , Humans , Uterine Cervical Neoplasms/drug therapy , Prospective Studies , Quality of Life , Neoplasm Staging , Chemoradiotherapy , Chemotherapy, Adjuvant/adverse effects , Adjuvants, Immunologic , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Retrospective StudiesABSTRACT
The cisplatin-based concurrent chemoradiotherapy (CCRT) has been accepted as a standard treatment for most locally advanced cervical cancer. Compared with radiation therapy alone, CCRT can increase tumor control and survival rates, whereas it also can increase the incidence of acute hematological toxicity, which results in the treatment interruption or delay, and may even affect clinical efficacy and prognosis of patients. Therefore, how to reduce the incidence and severity of acute hematological toxicity induced by CCRT is a hot spot of clinical research. Previous studies have demonstrated that the occurrence of hematological toxicity is associated with the volume and dose of irradiated pelvic bone marrow. With the development of modern radiotherapy technology, precise radiotherapy technologies, such as intensity-modulated radiotherapy (IMRT) and image-guided radiotherapy (IGRT), not only guaranteed the enough dose for tumor, but also realized the protection of normal tissues. This article will focus on the feasibility of bone marrow sparing during CCRT for cervical cancer, and summarize the research progress in recent years.
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Long-course concurrent chemoradiotherapy (CCRT) or short-course radiotherapy (SCRT) prior to surgery and postoperative chemotherapy is one of the main standard therapies for patients with locally advanced rectal cancer (LARC). On this basis, total neoadjuvant therapy (TNT) has been shown to improve disease-free survival, distant metastasis-free survival and complete response rates, whereas the 3-year distant recurrence rate is still above 20% and pathological complete response (pCR) is less than 30%. Long-term survival and adverse reactions remain to be improved. Currently, significant achivement has been obtained in immunotherapy. Application of immunotherapy in the treatment of rectal cancer remains to be urgently validated. In recent years, immunotherapy combined with preoperative chemoradiotherapy has been adopted for LARC in clinical trials. Besides, immunotherapy alone, especially programmed death-1 (PD-1) / programmed death ligand-1 (PD-L1) inhibitor, has also been utilized to treat colon rectal cancer. Relevant research progress was reviewed in this article.
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Objective:To construct machine learning models based on CT imaging and clinical parameters for predicting progression-free survival (PFS) of locally advanced cervical cancer (LACC) patients after concurrent chemoradiotherapy (CCRT).Methods:Clinical data of 167 LACC patients treated with CCRT at Shandong Cancer Hospital from September 2015 to October 2021 were retrospectively analyzed. All patients were randomly divided into the training and validation cohorts according to the ratio of 7 vs. 3. Clinical features were selected by univariate and multivariate Cox proportional hazards model ( P<0.1). Radiomics models and nomograms were constructed by radiomics features which were selected by least absolute shrinkage and selection operator (LASSO) Cox regression model to predict the 1-, 3- and 5-year PFS. Combined models and nomogram models were developed by selected clinical and radiomics features. The Kaplan Meier-curve, receiver operating characteristic (ROC) curve, C-index and calibration curve were used to evaluate the model performance. Results:A total of 1 409 radiomics features were extracted based on the region of interest (ROI) in CT images. CT radiomics models showed better performance for predicting 1-, 3-and 5-year PFS than the clinical model in the training and validation cohorts. The combined model displayed the optimal performance in predicting 1-, 3-and 5-year PFS in the training cohort [area under the curve (AUC): 0.760, 0.648, 0.661, C-index: 0.740, 0.667, 0.709] and verification cohort (AUC: 0.763, 0.677, 0.648, C-index: 0.748, 0.668, 0.678).Conclusions:Combined model constructed based on CT radiomics and clinical features yield better prediction performance than that based on radiomics or clinical features alone. As an objective image analysis approach, it possesses high prediction efficiency for PFS of LACC patients after CCRT, which can provide reference for clinical decision-making.
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Objective:To investigate the prognostic value of Onodera's prognostic nutrition index (PNI) before treatment in patients with cervical and upper thoracic esophageal squamous cell carcinoma (CUTESCC) undergoing definitive chemoradiotherapy (dCRT) and its predictive value in the occurrence of ≥ grade 2 radiation esophagitis (RE).Methods:The data of 163 CUTESCC patients eligible for inclusion criteria admitted to the Fourth Hospital of Hebei Medical University from January 2012 to December 2017 were retrospectively analyzed. The receiver operating characteristic (ROC) curve was used to calculate the best cut-off value of PNI for predicting the prognosis of patients. The prognosis of patients was analyzed by univariate and Cox multivariate analyses. Logistics binary regression model was adopted to analyze the risk factors of ≥ grade 2 RE in univariate and multivariate analyses. The significant factors in logistic multivariate analysis were used to construct nomogram for predicting ≥ grade 2 RE.Results:The optimal cut-off value of PNI was 48.57 [area under the curve (AUC): 0.653, P<0.001]. The median overall survival (OS) and progression-free survival (PFS) were 26.1 and 19.4 months, respectively. The OS ( χ2=6.900, P=0.009) and PFS ( χ2=9.902, P=0.003) of patients in the PNI ≥ 48.57 group ( n=47) were significantly better than those in the PNI < 48.57 group ( n=116). Cox multivariate analysis showed that cTNM stage and PNI were the independent predictors of OS ( HR=1.513, 95% CI: 1.193-1.920, P=0.001; HR=1.807, 95% CI: 1.164-2.807, P=0.008) and PFS ( HR=1.595, 95% CI: 1.247-2.039, P<0.001; HR=2.260, 95% CI: 1.439-3.550, P<0.001). Short-term efficacy was another independent index affecting PFS ( HR=2.072, 95% CI: 1.072-4.003, P=0.030). Logistic multivariate analysis showed that the maximum transverse diameter of the lesion ( OR=3.026, 95% CI: 1.266-7.229, P=0.013), gross tumor volume (GTV) ( OR=3.456, 95% CI: 1.373-8.699, P=0.008), prescription dose ( OR=3.124, 95% CI: 1.346-7.246, P=0.009) and PNI ( OR=2.072, 95% CI: 1.072-4.003, P=0.030) were the independent factors affecting the occurrence of ≥ grade 2 RE. These four indicators were included in the nomogram model, and ROC curve analysis showed that the model could properly predict the occurrence of ≥ grade 2 RE (AUC=0.686, 95% CI: 0.585-0.787). The calibration curve indicated that the actually observed values were in good agreement with the predicted RE. Decision curve analysis (DCA) demonstrated satisfactory nomogram positive net returns in most threshold probabilities. Conclusions:PNI before treatment is an independent prognostic factor for patients with CUTESCC who received definitive chemoradiotherapy. The maximum transverse diameter of the lesion, GTV, prescription dose and PNI are the risk factors for ≥ grade 2 RE in this cohort. Establishing a prediction model including these factors has greater predictive value.
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Objective:To evaluate the value of chemoradiotherapy and surgery in cervical esophageal cancer (CEC).Methods:Data of 459 patients with CEC from 2004 to 2017 were collected and retrospectively analyzed from the surveillance, epidemiology, and end results (SEER) database of National Cancer Institute (US). All patients were divided into the chemoradiotherapy group ( n=379) and surgery group ( n=80) according to the treatment methods. Survival analysis was performed by Kaplan-Meier method and survival curve was drawn. Multivariate survival analysis was conducted by Cox proportional hazards regression model. The death rate of different causes between two groups was calculated by cumulative incidence function (CIF). The differences of death rate between two groups were evaluated by Fine-Gray competing risk model. By analyzing the clinical characteristics and survival of CEC patients, the overall survival (OS) was compared between the surgery and chemoradiotherapy groups. Results:The 2- and 5-year survival rates in the chemoradiotherapy group were 43.1% and 22.4%, while those of the surgical group were 46.8% and 26.0%, respectively. No significant difference was observed in the OS between the chemoradiotherapy and surgery groups ( P=0.750). Cox multivariate analysis showed that treatment (surgery group vs. chemoradiotherapy group) was not an independent prognostic factor for OS. Based on the results of competing risk analysis, the risk of esophageal cancer-specific death in the chemoradiotherapy group was higher than that in the surgery group, and the difference was statistically significant between two groups ( P<0.001). The risk of other cause-specific death in the chemoradiotherapy group was lower than that in the surgery group ( P<0.001). The proportion of patients who died of oral, oropharyngeal, hypopharyngeal and laryngeal diseases in the surgery group was significantly higher than that in the chemoradiotherapy group(all P<0.001). Conclusions:No significant difference is observed in the OS of CEC patients treated with chemoradiotherapy or surgery. In the surgery group, the risk of esophageal cancer-specific death is lower, whereas the risk of other cause-specific death is higher compared with those in the chemoradiotherapy group.
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Objective:To analyze the fail mode of neoadjuvant therapy combined with surgery for locally advanced esophageal squamous cell carcinoma (ESCC) after long-term follow-up.Methods:Clinical data of consecutive 238 patients with locally advanced resectable ESCC who underwent neoadjuvant therapy combined with surgery in Zhejiang Cancer Hospital from September 2012 to October 2019 were retrospectively analyzed. The failure mode in the whole cohort was analyzed after long-term follow-up. The overall survival (OS) and disease free survival (DFS) rates were analyzed by Kaplan-Meier method. Survival differences were determined by log-rank test.Results:The pathological complete response (pCR) rate was 42.0% in 238 patients. After a median follow-up of 46.1 months, tumor progression occurred in 96 patients (40.3%), including 25 patients (10.5%) with local recurrence, 61 patients (25.6%) with distant metastases, and 10 patients (4.2%) with simultaneous local recurrence and distant metastases. The median OS and DFS were 64.7 months and 49.9 months. And the 3-, 5-, and 7-year OS and DFS rates were 70.0%, 52.8%, 36.4% and 63.5%, 42.5%, and 30.0%, respectively. The 3-, 5-, and 7-year locoregional recurrence-free survival rates and distant metastasis-free survival rates were 86.0%, 71.4%, 61.2% and 70.6%, 55.9%, 43.0%. Compared with non-pCR patients, the overall progression rate and distant metastasis rate of pCR patients were lower (26.0% vs. 50.7%, 16.0% vs. 32.6%, both P<0.05). And the 3-, 5-, and 7-year OS (83.0% vs. 60.2%, 69.7% vs. 41.7%, 50.4% vs. 27.7%, all P<0.001) and DFS rates (80.4% vs. 51.4%, 63.9% vs. 31.2%, 45.9% vs. 20.3%, all P<0.001) were significantly better in pCR patients. Conclusions:Distant metastasis is the main failure mode of patients with locally advanced ESCC after neoadjuvant therapy. Patients with postoperative pCR can achieve better long-term survival.
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With the aging of population, the elderly (≥65 years old) cancer patients have become one of the main populations for cancer care. For inoperable locally advanced head and neck squamous carcinomas, cisplatin-based concurrent chemoradiotherapy is the first-line choice. Several large clinical studies have shown that patients under 70 years of age can still benefit from concurrent chemoradiotherapy, while it should be cautious to apply chemotherapy to patients aged 70-80 years. For elderly patients who are intolerant to cisplatin, carboplatin or other regimens with less gastrointestinal and renal toxicity should be considered. Although anti-epidermal growth factor receptor (EGFR) monoclonal antibodies combined with radiotherapy has been proved to be more effective than radiotherapy alone in total patient population, age-subgroup analysis showed limited benefit in elderly patients. The safety of immune checkpoint inhibitors in elderly patients has been validated and those with high programmed death ligand-1 (PD-L1) expression may benefit from concurrent or neoadjuvant immunotherapy, however, high-level evidence is still lacking. For patients older than 80 years, radiotherapy alone may be superior to concurrent chemoradiotherapy, and hypofractionated radiotherapy for palliative purposes can be safely used in this population.
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For locally advanced (T 3-4/N +M 0) rectal cancer (LARC), neoadjuvant chemoradiotherapy (nCRT) followed by total mesorectal excision (TME) is the standard treatment, which have been demonstrated to decrease the local recurrence rate and increase the tumor response grade. However, the distant metastasis remains an unresolved issue. Radiotherapy and immunotherapy can supplement each other and the combination of the two treatments has a good theoretical basis. Recently, multiple clinical trials are ongoing in terms of the combination of nCRT and immunotherapy in LARC. These trials have achieved promising short-term efficacy in both microsatellite instability-high (MSI-H) and microsatellite stable (MSS) rectal cancers, which could further improve the rate of tumor response and rate of pathological complete response, increase the possibility of organ preservation and "watch and wait" approach. Large-scale clinical trials need to be performed in the future to demonstrate these findings and to improve long-term prognosis.
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Objective:To investigate the value of nomograms based on clinical parameters, apparent diffusion coefficient (ADC) and MRI-derived radiomics in predicting survival of patients with locally advanced cervical cancer (LACC) after concurrent chemoradiotherapy (CCRT).Methods:Clinical data of 423 patients with IB-IVA cervical cancer treated with CCRT at Anhui Provincial Hospital Affiliated to Anhui Medical University from March 2014 to March 2020 were retrospectively analyzed and randomly divided into the training and validation groups at a ratio of 2∶1 using the simple randomization method. The values of ADC min, ADC mean, ADC max and 3D texture parameters of diffusion weighted imaging (DWI), T 2WI, T 2WI-fat suppression of pre-treatment primary lesions in all patients were measured. The least absolute shrinkage and selection operator (LASSO) algorithm and logistic regression analysis were used to screen the texture features and calculate radiomics score (Rad-score). Cox regression analysis was employed to construct nomogram models for predicting overall survival (OS) and cancer-specific survival (CS) of patients with LACC after CCRT, which were subject to internal and external validation. Results:Squamous cell carcinoma antigen (SCC-Ag), external beam radiotherapy dose, ADCmin and Rad-score were the independent prognostic factors for OS and CS of LACC patients after CCRT and constituted predictive models for OS and CS. The area under the receiver operating characteristic (ROC) curve (AUC) of two models in predicting 1-year, 3-year, 5-year OS and CS was 0.906, 0.917, 0.916 and 0.911, 0.918, 0.920, with internally validated consistency indexes (C-indexes) of 0.897 and 0.900. Then, models were brought into the validation group for external validation with AUC of 0.986, 0.942, 0.932 and 0.986, 0.933, 0.926 in predicting 1-year, 3-year, 5-year OS and CS.Conclusion:The nomograms based on clinical parameters, ADC values and MRI-derived radiomics are of high clinical value in predicting OS and CS of patients with LACC after CCRT, which can be used as prognostic markers for patients with cervical cancer to certain extent.
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Objective:To analyze the local recurrence patterns after concurrent chemoradiotherapy (CCRT) for thoracic esophageal squamous cell carcinoma (ESCC) through image fusion, and to explore the risk factors of local recurrence and its relationships with dosimetric indices.Methods:A retrospective analysis was conducted for 209 thoracic ESCC patients who received radical CCRT in Fourth Hospital of Hebei Medical University during 2016-2019. For the patients diagnosed as the local recurrence of esophageal lesions, their CT images were fused with the original planning CT images using image registration software to identify the recurrence sites. Through 1∶1 propensity score matching (PSM) of the clinal data of patients with local recurrence (the recurrence group, nbefore = 81, nafter = 62) and those without local recurrence (the recurrence-free group, nbefore = 128, nafter=62), the dose and volume parameters of the treatment plans for the two groups were compared. Univariate and multivariate analyses were conducted using the Kaplan-Meier method and the Cox regression model to analyze the factors affecting the overall survival (OS), progression-free survival (PFS), and recurrence-free survival (RFS). Results:All patients had 1-, 3-, and 5-year OS rates of 80.9%, 42.6%, and 33.0%, respectively, 1-, 3-, and 5-year PFS rates of 67.9%, 34.0%, and 27.9%, respectively, and 1-, 3-, and 5-year RFS rates of 71.3%, 39.2%, and 30.5%, respectively. T stage, N stage, and radiation dose were independent prognostic factors for the OS, PFS, and RFS ( HR = 1.42-1.87, P < 0.05) of the patients, respectively. Among 68 patients with local recurrence, 62 cases (91.2%) suffered recurrence within the gross tumor volume (GTV). The dose and volume parameters of patients with local recurrence, such as GTV- D95%, clinical target volume (CTV)- D95%, GTV- D50%, CTV- D50%, and planning target volume (PTV)- D50%, GTV- V60, CTV- V60, and PTV- V60, were significantly lower than those of patients free from the local recurrence ( t=1.90-2.15, P < 0.05). Conclusions:Local recurrence of patients with thoracic ESCC after radical CCRT occurs mainly within the GTV. Increasing radiation doses may contribute to their survival benefits. The D50% for each target volume in the radiotherapy plan may be related to local recurrence, and it is necessary to conduct further research.
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Objective:To analyze the correlation between the volume of irradiated pelvic bone marrow and acute hematologic toxicity (HT), in order to provide clinical data to reduce the risk of acute HT and optimize the radiotherapy plan.Methods:From October 2017 to May 2019, 41 LARC patients who received neoadjuvant concurrent chemoradiotherapy (CCRT) were retrospectively reviewed in our center. All patients were treated with 5-field intensity-modulated radiotherapy (IMRT), and the prescription dose delivered to PTV was 45-50.4 Gy in 25-28 fractions. Capecitabine or 5-fluorouracil (5-FU) wasadministered daily 5 days a week during radiotherapy. Different HTswere recorded according to National Cancer Institute Common Toxicity Criteria Version 5.0 (NCI-CTC.V5.0) based on laboratory tests. The volume of PBM or each site (coxal, sacrum, femoral) receiving more than x Gy refers to as TVx, CVx, SVx, and FVx, respectively. Logistic regression was performed to evaluate the association between the volume of irradiated pelvic bone marrow and different HT. Generalized additive model (GAM) and piecewise regression were used to further analyze the possible nonlinear relationship and threshold effect between them. Results:Multivariate logistic regression analysis showed that low-dose of irradiated total pelvic bone marrow volume ( TV5) and coxal bone marrow volume ( CV5, CV10) were significantly correlated with Grade ≥2 leukopenia( P<0.05). There was a significant negative correlation between the sacrum bone marrow volume ( SV5, SV10) and Grade ≥2 leukopenia ( P<0.05). A thresholdeffect has been observed between CV10 and Grade ≥2 leukopenia by Generalized additive model (GAM) and piecewise linear regression. The threshold between CV10 and Grade ≥2 leukopenia was 575 ml, OR (95% CI) was 1.85 (1.08, 3.16). Conclusions:In neoadjuvant IMRT of rectal cancer, CV is a better predictor of acute HT induced by CCRT than TV. The irradiated volume of CV associated with acute HT was mainly low-dose levels ( CV5, CV10). The thresholds of our study ( CV10= 575 ml) could be a good reference for the optimization of the radiotherapy plan.
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Objective:To explore the establishment and application of ovarian cancer organoids.Methods:Fresh ovarian tumor tissues, obtaining from patients underwent surgery in the First Affiliated Hospital of Nanjing Medical University between October 2021 and March 2022, were collected, enzymatic degraded, digested, and embedded into matrigel to establish organoids. A total of 32 ovarian cancer samples were collected. Hematoxylin eosin (HE) staining and immunofluorescence (IF) procedure were used to verify the morphological structure of organoids and their expression of molecular markers. 3D cyto-live or dead assay was used to detecte the live or dead cells in organoids. Carboplatin with a concentration ranging from 5 to 80 μmol/L (5, 10, 20, 40, 80 μmol/L) was added to organoids to calculate the 50% inhibitory concentration (IC 50) in different organoids. Results:(1) Organoids from a total of 32 patients were established, of which 18 cases could be passaged stably in the long term in vitro, while 14 could be passaged in the short time. The average amplification time of long-term passage in vitro was over 3 months, and the longest reached 9 months. (2) In HE staining, significant nuclei atypia and local micropapillary structures were observed in organoids. IF staining revealed that ovarian cancer organoids expressed molecular markers similar to primary tumor tissues, such as Pan cytokeratin (Pan-CK), p53, paired box gene 8 (PAX8), and Wilms tumor gene 1 (WT1). (3) In 3D cyto-live or dead assay, a large number of apoptotic cells were observed inside and around the organoids after added carboplatin. The sensitivity to carboplatin varied in 18 organoids could amplify in the long term, with an average IC 50 of (29.5±15.8) μmol/L. Moreover, IC 50 values of 4 organoids derived from patients received neoadjuvant chemotherapy were much higher than the 14 organoids which did not received neoadjuvant chemotherapy [(48.7±11.3) μmol/L vs (24.0±12.1) μmol/L; t=3.429, P=0.022]. Conclusions:Organoids recapitulate ovarian cancers in vitro and could be stably passaged. Organoids derived from patients received neoadjuvant chemotherapy have higher resistance to carboplatin.
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Malignant mesothelioma of the tunica vaginalis testis (MMTVT) is a rare tumor. At present, there are still many disputes in its epidemiology, pathogenesis, selection of diagnostic methods, treatment and prognosis. Asbestos exposure, ionizing radiation and chromosome abnormalities are the risk factors of MMTVT. Immunohistochemistry, ultrasonography and electron microscope can be used for the diagnosis and aggressive surgery is the main treatment method. The development of endoscopic surgery, multi-disciplinary treatment (MDT), tumor targeted therapy and immunotherapy will bring more benefits to MMTVT patients.
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Objective To investigate whether sarcopenia before concurrent chemoradiotherapy is prone to grade≥3 acute adverse reactions (AAR) and shorten survival in patients with advanced esophageal squamous cell carcinoma (ESCC). Methods Data of advanced patients with pathologically diagnosed ESCC and CCRT (FP regimen) from August 2018 to July 2022 were reviewed retrospectively.Skeletal muscle mass and body composition were measured using pre-treatment CT images, and patients were divided into sarcopenia and non-sarcopenia groups.Grade≥3 AAR was diagnosed based on CTCAE5.0 and acute radiation injury criteria of the US RTOG.Risk factors for developing grade≥3 AAR were analyzed, and survival rates were calculated by Kaplan-Meier method. Results Among 132 patients with ESCC (87 in the sarcopenia group and 45 in the non-sarcopenia group), 23(17.4%) experienced grade≥3 AAR.In multivariate regression analysis, independent risk factors for grade ≥3 AAR included the following: sarcopenia (OR: 6.034, 95%CI: 1.206-30.190, P=0.029), decreased SMD (OR: 0.693, 95%CI: 0.492-0.976, P=0.036), decreased SMI (OR: 0.841, 95%CI: 0.721-0.982, P=0.028), and increased FMI (OR: 2.433, 95%CI: 1.194-4.958;P=0.014).The OS rates were 16.01 months (95%CI: 14.89-17.13) in the sarcopenia group and 19.27 months (95%CI: 14.45-24.09) in the non-sarcopenia group (χ2=5.326, P=0.021) as well as 14.86 months (95%CI: 11.30-18.42) for patients with grade≥3 AAR and 16.67 months (95%CI: 14.91-18.43) for patients with grade 0-2 AAR (χ2=5.47, P=0.019).Among patients with grade≥3 AAR, the OS rates were 12.13 months (95%CI: 10.15-14.11) in the sarcopenia group and 18.69 months (95%CI: 12.85-21.88) in the non-sarcopenia group (χ2=4.466, P=0.035). Conclusion Sarcopenia, decreased skeletal muscle density, and increased fat mass are important predictors of grade≥3 AAR.The OS of patients with sarcopenia and grade≥3 AAR may be reduced.