Abrasive challenge effects on enamel and dentin from irradiated human teeth: an in vitro study.

This study aimed to evaluate the effects of radiotherapy (RT) and chemoradiotherapy (CRT) on the wear and surface roughness of in vitro irradiated human enamel and dentin subjected to abrasive challenge. Enamel and dentin specimens (n = 42) were prepared from teeth donated by healthy patients and those with head and neck cancer who had received radiotherapy (RT) or chemoradiotherapy (CRT). The specimens were categorized into three groups: control, RT, and CRT (n = 14 per group for both enamel and dentin). These samples were subjected to an in vitro abrasive experiment using a brushing machine, followed by wear and surface roughness assessments with a confocal laser scanning microscope conducted before and after the abrasive challenge, considering both exposed and non-exposed areas. Statistical analysis used Shapiro-Wilk tests for normality, Wilcoxon tests for comparing two means, and Kruskal-Wallis tests. A significance level of 5% was adopted. In enamel specimens, wear profile values ​​of CRT and RT groups were not different from the control (p > 0.05). The RT group presents lower step values than the CRT and control groups (p < 0.001). No significant difference in final surface roughness was observed in all groups (p > 0.05). In dentin specimens, no significant difference in wear profile and step was observed in all groups (p > 0.05). However, CRT and RT groups present higher values in final surface roughness (p < 0.001). The exposure to ionizing radiation (associated or not to chemotherapy) influenced the surface roughness of dentin and the wear (step) of enamel after the in vitro abrasive challenge.Trial registration: Ethical procedures were approved by the FORP/USP Research Ethics Committee (CAAE: 61308416.4.0000.5419), and Hospital do Câncer de Barretos/Fundação Pio XII (CAAE: 61308416.4.3001.5437).

Prognostic factors for local recurrence in patients with rectal cancer submitted to neoadjuvant chemoradiotherapy and total mesorectal excision.

Prognostic factors for local recurrence in patients with rectal cancer submitted to neoadjuvant chemoradiotherapy and total mesorectal excision. BACKGROUND: The standard curative treatment for locally advanced rectal cancer of the middle and lower thirds is long-course chemoradiotherapy followed by total mesorectal excision. PURPOSE: To evaluate the prognostic factors associated with local recurrence in patients with rectal cancer submitted to neoadjuvant chemoradiotherapy and total mesorectal excision. METHODS: Retrospective study including patients with rectal cancer T3-4N0M0 or T (any)N + M0 located within 10 cm from the anal border, or patients with T2N0M0 located within 5 cm, treated by long course chemoradiotherapy followed by total mesorectal excision with curative intent. Clinical, demographic, radiologic, surgical, and anatomopathological data were collected. Local recurrence was estimated using the Kaplan-Meier function, and risk was estimated according to each characteristic using univariate and multivariate analyses. RESULTS: 270 patients were included, 57.8% male and mean age 61.7 (30‒88) years. At initial staging, 6.7% of patients were stage I, 21.5% stage II, and 71.8% stage III. Open surgery was performed in 65.2%, with sphincter preservation in 78.1%. Mortality within 30 postoperative days was 0.7%. After 49.4 (0.5‒86.1) months of median follow-up, overall and local recurrences were 26.3% and 5.9%. On multivariate analyses, local recurrence was associated with involvement of the mesorectal fascia on restaging MRI (HR = 9.11, p = 0.001) and with pathologic involvement of radial surgical margin (HR = 8.19, p < 0.001). CONCLUSION: Local recurrence of rectal cancer treated with long-course chemoradiation and total mesorectal excision is low and is associated with pathologic involvement of the radial surgical margin and can be predicted on restaging MRI.

Impact of a comprehensive geriatric assessment to manage elderly patients with locally advanced non-small-cell lung cancers: a multicenter prospective study.

PURPOSE: Concurrent chemoradiotherapy (cCRT) is the standard treatment for locally advanced and unresectable non-small-cell lung cancer. Population is aging, and Geriatric assessment (GA) has demonstrated its paper to select fit patients for active treatment and vulnerable, frail patients for interventions and/or palliative care in many histologies. Its role in locally advanced, unresectable non-small-cell lung cancer has been less explored. METHODS: To assess the capability of GA to detect frail patients not suitable for active treatment, we developed this exploratory non-interventional prospective study. All patients ≥ 70 years diagnosed with stage locally advanced and unresectable non-small-cell lung cancer were invited to undergo geriatric assessment. Secondary aims were description of population, exploring GA as prognostic factor, determination of toxicity profile and look for a frailty biomarker. RESULTS: From June 2017 to June 2020, 51 patients were included, of whom 35% (n:18) were classified as frail. Frail patients had less overall survival and more grade 3-4 toxicity. Exploratory results for frailty phenotype are described in the text. CONCLUSIONS: With the results of our study, we confirm that GA can detect frail patients unsuitable for treatment, with a higher risk of toxicity and less overall survival. A trend toward blood-test results for phenotype frailty can be hypothesis generation.

Identification of radiologic and clinicopathologic variables associated with tumor regression pattern and distribution of cancer cells after short-course radiotherapy and consolidation chemotherapy in patients with rectal cancer.

Background: Knowledge of the pattern of regression and distribution of residual tumor cells may assist in the selection of candidates for rectum-sparing strategies. Objective: To investigate and identify factors associated with tumor regression pattern and distribution of residual tumor cells. Methods: We conducted a prospective study of patients with T3/T4 N0/N+ adenocarcinoma of the middle and lower third of the rectum (≤10 cm) treated with radiotherapy (5×5 Gy) followed by 6 cycles of CAPOX chemotherapy. The pattern of tumor regression was classified as fragmented or solid. Microscopic intramural spread was measured. We used a model of distribution of residual tumor cells not yet applied to rectal cancer, defined as follows: type I (luminal), type II (invasive front), type III (concentric), and type IV (random). Results: Forty patients were included with a median age of 66 years; 23 (57.5%) were men. A fragmented pattern was identified in 18 patients (45.0%), and a solid pattern in 22 (55.0%). Microscopic intramural spread was identified in 25 patients (62.5%), extending from 1 to 18 mm (median, 4 mm). There were 14 cases (35.0%) of microscopic intramural spread ≥10 mm. All cases of fragmented regression pattern, except one, showed microscopic intramural spread. Within the fragmented pattern, microscopic intramural spread was 4-8 mm in 4 cases and ≥10 mm in the remaining cases. All cases of microscopic intramural spread ≥ 10 mm were within the fragmented pattern. Regarding the distribution pattern of residual tumor cells, 11 cases (31.5%) were classified as type I, 14 (40.0%) as type II, 10 (28.5%) as type III, and none as type IV. Carcinoembryonic antigen levels >5 ng/mL, downsizing <50%, residual mucosal abnormality >20 mm, and anatomopathologic lymph node involvement were significantly associated with the occurrence of fragmentation (P<0.05). Having received all 6 cycles of CAPOX chemotherapy and absence of microscopic intramural spread were significantly associated with the type I distribution pattern (P<0.05). Conclusion: The occurrence of a fragmented regression pattern is common, as is the presence of microscopic intramural spread. We could identify radiologic and clinicopathologic factors associated with the pattern of tumor regression and a type I distribution pattern.

Brazil-TNT: A Randomized Phase 2 Trial of Neoadjuvant Chemoradiation Followed by FOLFIRINOX Versus Chemoradiation for Stage II/III Rectal Cancer.

BACKGROUND: Neoadjuvant radiation and oxaliplatin-based systemic therapy (total neoadjuvant therapy-TNT) have been shown to increase response and organ-preservation rates in localized rectal cancer. However, trials have been heterogeneous regarding treatment protocols and few have used a watch-and-wait (WW) approach for complete responders. This trial evaluates if conventional long-term chemoradiation followed by consolidation of FOLFIRINOX increases complete response rates and the number of patients managed by WW. METHODS: This was a pragmatic randomized phase II trial conducted in 2 Cancer Centers in Brazil that included patients with T3+ or N+ rectal adenocarcinoma. After completing a long-course 54 Gy chemoradiation with capecitabine patients were randomized 1:1 to 4 cycles of mFOLFIRINOX (Oxaliplatin 85, irinotecan 150, 5-FU 2400)-TNT-arm-or to the control arm, that did not include further neoadjuvant treatment. All patients were re-staged with dedicated pelvic magnetic resonance imaging and sigmoidoscopy 12 weeks after the end of radiation. Patients with a clinical complete response were followed using a WW protocol. The primary endpoint was complete response: clinical complete response (cCR) or pathological response (pCR). RESULTS: Between April 2021 and June 2023, 55 patients were randomized to TNT and 53 to the control arm. Tumors were 74% stage 3, median distance from the anal verge was 6 cm, 63% had an at-risk circumferential margin, and 33% an involved sphincter. The rates of cCR + pCR were (31%) for TNT versus (17%) for controls (odds ratio 2.19, CI 95% 0.8-6.22 P = .091) and rates of WW were 16% and 9% (P = ns). Median follow-up was 8.1 months and recurrence rates were 16% versus 21% for TNT and controls (P = ns). CONCLUSIONS: TNT with consolidation FOLFIRINOX is feasible and has high response rates, consistent with the current literature for TNT. This trial was supported by a grant from the Brazilian Government (PROADI-SUS - NUP 25000.164382/2020-81).

LC-MS metabolomics analysis of serum metabolites during neoadjuvant chemoradiotherapy in locally advanced rectal cancer.

BACKGROUND: This study aimed to investigate the serum metabolite profiles during neoadjuvant chemoradiotherapy (NCRT) in locally advanced rectal cancer (LARC) using liquid chromatography-mass spectrometry (LC-MS) metabolomics analysis. METHODS: 60 serum samples were collected from 20 patients with LARC before, during, and after radiotherapy. LC-MS metabolomics analysis was performed to identify the metabolite variations. Functional annotation was applied to discover altered metabolic pathways. The key metabolites were screened and their ability to predict sensitivity to radiotherapy was calculated using random forests and ROC curves. RESULTS: The results showed that NCRT led to significant changes in the serum metabolite profiles. The serum metabolic profiles showed an apparent separation between different time points and different sensitivity groups. Moreover, the functional annotation showed that the differential metabolites were associated with a series of important metabolic pathways. Pre-radiotherapy (3Z,6Z)-3,6-Nonadiena and pro-radiotherapy 1-Hydroxyibuprofen showed good predictive performance in discriminating the sensitive and non-sensitive group to NCRT, with an AUC of 0.812 and 0.75, respectively. Importantly, the combination of different metabolites significantly increased the predictive ability. CONCLUSION: This study demonstrated the potential of LC-MS metabolomics for revealing the serum metabolite profiles during NCRT in LARC. The identified metabolites may serve as potential biomarkers and therapeutic targets for the management of this disease. Furthermore, the understanding of the affected metabolic pathways may help design more personalized therapeutic strategies for LARC patients.

Effects of prebiotics, probiotics, and synbiotics on the prevention and treatment of cervical cancer: Mexican consensus and recommendations.

Gut microbiota plays a crucial role in modulating immune responses, including effector response to infection and surveillance of tumors. This article summarizes the current scientific evidence on the effects of supplementation with prebiotics, probiotics, and synbiotics on high-risk human papillomavirus (HPV) infections, precancerous lesions, and various stages of cervical cancer development and treatment while also examining the underlying molecular pathways involved. Our findings indicate that a higher dietary fiber intake is associated with a reduced risk of HPV infection, while certain probiotics have shown promising results in clearing HPV-related lesions. Additionally, certain strains of probiotics, prebiotics such as inulin and fructo-oligosaccharides, and synbiotics decrease the frequency of gastrointestinal adverse effects in cervical cancer patients. These agents attain their results by modulating crucial metabolic pathways, including the reduction of inflammation and oxidative stress, promoting apoptosis, inhibiting cell proliferation, and suppressing the activity of oncogenes, thus attenuating tumorigenesis. We conclude that although further human studies are necessary, robust evidence in preclinical models demonstrates that prebiotics, probiotics, and synbiotics play an essential role in cervical cancer, from infection to carcinogenesis and its medical treatment. Consequently, we strongly recommend conducting high-quality clinical trials using these agents as adjuvants since they have proven safe.

The S-REAL study: Spanish real-world data on unresectable stage III NSCLC patients treated with durvalumab after chemoradiotherapy.

OBJECTIVES: The S-REAL study aimed to assess the effectiveness of durvalumab as consolidation therapy after definitive chemoradiotherapy (CRT) in a real-world cohort of patients with locally advanced, unresectable stage III non-small cell lung cancer (LA-NSCLC) included in a Spanish early access program (EAP). METHODS: In this multicentre, observational, retrospective study we analysed data from patients treated in 39 Spanish hospitals, who started intravenous durvalumab (10 mg/kg every 2 weeks) between September 2017 and December 2018. The primary endpoint was progression-free survival (PFS). Secondary endpoints included patient characterization and adverse events of special interest (AESI). RESULTS: A total of 244 patients were followed up for a median of 21.9 months [range 1.2-34.7]. Median duration of durvalumab was 45.5 weeks (11.4 months) [0-145]. Median PFS was 16.7 months (95% CI 12.2-25). No remarkable differences in PFS were observed between patients with programmed cell death-ligand 1 (PD-L1) expression ≥ 1% or < 1% (16.7 versus 15.6 months, respectively). However, PFS was higher in patients who had received prior concurrent CRT (cCRT) versus sequential CRT (sCRT) (20.6 versus 9.4 months). AESIs leading to durvalumab discontinuation were registered in 11.1% of patients. CONCLUSIONS: These results are in line with prior published evidence and confirm the benefits of durvalumab in the treatment of LA-NSCLC patients in a real-world setting. We also observed a lower incidence of important treatment-associated toxicities, such as pneumonitis, compared with the pivotal phase III PACIFIC clinical study.

Current status of neoadjuvant immunotherapy for the treatment of gastric cancer.

Gastric cancer is one of the most prevalent malignant tumors worldwide, characterized by high incidence and mortality rates. At present, comprehensive surgical treatment has enhanced the prognosis of locally advanced gastric cancer patients significantly. However, the postoperative recurrence rate remains high, and the long-term survival for patients is sub-optimal. In recent years, immunotherapy has garnered extensive attention as an innovative approach to the treatment of gastric cancer. Indeed, multiple studies have validated its therapeutic effects in advanced gastric cancer patients, leading to its incorporation into treatment guidelines. Currently, researchers are exploring the application of immunotherapy in the neoadjuvant setting globally in order to further adjust and refine neoadjuvant immunotherapy regimens for gastric cancer. This article summarizes the research progress and controversies associated with neoadjuvant immunotherapy in gastric cancer, aiming to optimize clinical benefits for gastric cancer patients undergoing this treatment approach. The retrieval methods of this study encompassed databases such as PubMed, Google Scholar, Web of Science, clinicaltrials.gov, etc. The retrieved articles included guidelines, consensus, meta-analyses, clinical trials, and reviews related to locally advanced gastric cancer published up to January 2024.

Single Nucleotide Polymorphisms as Biomarker Predictors of Oral Mucositis Severity in Head and Neck Cancer Patients Submitted to Combined Radiation Therapy and Chemotherapy: A Systematic Review.

Single Nucleotide Polymorphisms (SNPs) are the most common type of genetic variation found in an individual's DNA sequences. SNPs can occur in both coding and non-coding regions of the genome and can affect gene expression, protein function, and disease susceptibility. In this systematic review, we evaluate the potential of SNPs as biomarkers in the assessment of oral mucositis (OM) severity in head and neck cancer (HNC) patients treated with concomitant chemoradiation (CRT). The study selection process involved screening 66 articles from different platforms, and after removing duplicates and excluding articles that did not meet the eligibility criteria, 23 articles were included for full-text evaluation. Among them, genes from several pathways were analyzed. The DNA damage repair pathways had the highest number of genes studied. The most frequently analyzed gene was XRCC1. The proinflammatory cytokine pathways evaluated were TNF, with three articles, and NF-κB, with one article. Most included studies showed a potential association between certain SNPs and high-grade mucositis. We conclude that SNPs can be used as possible biomarkers for the assessment of OM intensity in HNC patients, and further research is needed to explore the potential of SNPs in personalized medicine for HNC treatment.

The ypT may better predict the efficacy of neoadjuvant chemoradiotherapy than tumor regression grade in locally advanced rectal cancer patients diagnosed ypT1-4N0.

PURPOSE: This study aimed to assess the impact of ypT stage and tumor regression grade (TRG) on the long-term prognosis of patients with locally advanced rectal cancer (LARC) stage ypT1-4N0 after neoadjuvant chemoradiotherapy (NCRT). METHODS: We retrospectively analyzed 585 patients with histologically diagnosed middle-low LARC (cT3-4 or cN + by pelvic MRI) from 2014 to 2019. All patients underwent NCRT, followed by total mesorectal excision. Disease-free survival (DFS) rates were compared among patients with different ypT stages and TRGs by Kaplan-Meier survival analysis. The chi-square test was used to analyze the relationship between clinicopathological or therapeutic factors and ypT stage. RESULTS: The median follow-up was 35.8 months (range 2.8-71.8 months). The 3-year DFS was 79.5%. A better 3-year DFS was achieved in patients with a pathologic complete response (94.0% vs. 74.3%, p < 0.001) and those in the ypT0-2 (86.5% vs. 66.6%, p < 0.001), ypN0 (85.0% vs. 60.2%, p < 0.001), and TRG0 + 1 (83.1% vs. 73.0%, p = 0.004) subgroups. A total of 309 patients (52.8%) achieved stage ypT1-4N0 after surgery. Among these patients, the ypT1-2N0 subgroup achieved a significantly higher 3-year DFS than the ypT3-4N0 subgroup (85.4% vs. 72.8%, p = 0.018); in contrast, the 3-year DFS did not significantly differ between the TRG1 and TRG2 + 3 subgroups (79.9% vs. 81.1%, p = 0.833). In the ypT1-2N0 or ypT3-4N0 subgroup, different TRG had no significant effect on failure patterns. CONCLUSIONS: For LARC patients with a ypT1-4N0 status after NCRT, ypT stage may be a more effective predictor of long-term prognosis than TRG.

Evaluación de respuesta a la quimiorradioterapia en carcinomas no microcíticos de pulmón en estadios iniciales

Introducción: El cáncer de pulmón representa la causa más común de muerte por enfermedades malignas en el mundo. La tasa de respuesta al tratamiento es pobre aún en estadios iniciales y depende de varios elementos. Objetivo: Evaluar la respuesta a la quimiorradioterapia en carcinomas de pulmón en estadios iniciales según hábito de fumar, histología y etapa clínica al diagnóstico. Materiales y métodos: Se realizó un estudio de evaluación, analítico, transversal, retrospectivo. El universo estuvo constituido por los 45 pacientes con diagnóstico citohistológico de cáncer de pulmón de células no pequeñas en etapas desde la IA a la IIIA, que recibieron tratamiento de primera línea con quimiorradioterapia, atendidos en el Centro Oncológico Provincial de Matanzas, en el período de enero de 2017 a diciembre de 2019. Resultados: Se obtuvo respuesta completa en un 36,6 % de los no fumadores y en el 25 % de los fumadores. En cuanto a respuesta completa a la quimiorradioterapia de los tumores de pulmón según histología, en los adenocarcinomas fue del 10 %; en los epidermoides, 22,6 %, y en los adenoescamosos, 50 %. En etapas IA-IB presentó respuesta completa el 50 % de los casos, en las IIA-IIB el 37,5 %, mientras que en la IIIA predominó la respuesta parcial. Conclusiones: Los mejores porcientos de respuesta completa se obtuvieron en los no fumadores, con tipo histológico adenoescamoso y en etapas IA-IB.

Introduction: Lung cancer is the most common cause of death from malignant diseases in the world. The response rate to treatment is poor even in the initial stages and depends on several elements. Objective: To evaluate the response to chemoradiotherapy in lung carcinomas in early stages according to smoking habit, histology and clinical stage at diagnosis. Materials and method: An analytical, cross-sectional, retrospective evaluation study was carried out; the universe consisted of 45 patients with a cytohistological diagnosis of non-small cell lung cancer in stages from IA to IIIA, who received first-line treatment with chemoradiotherapy, attended at the Provincial Cancer Center of Matanzas, in the period of January 2017 to December 2019. Results: A complete response was obtained in 36.6% of non-smokers and in 25% of smokers. Regarding complete response to chemoradiotherapy of lung tumors according to histology, in adenocarcinomas it was 10%, in epidermoids, 22.6%, and in adenosquamous cell, 50%. In stages IA-IB, 50% of the cases presented a complete response, in stages IIA-IIB, 37.5%, while in IIIA partial response predominated. Conclusions: The best percentages of complete response were obtained in non-smokers, with adenosquamous histology type and in stages IA-IB.

Quimioterapia perioperatória, quimioterapia adjuvante e quimiorradioterapia adjuvante no tratamento cirúrgico do câncer gástrico em um hospital do sistema único de saúde brasileiro / Perioperative chemotherapy, adjuvant chemotherapy and adjuvant chemoradiotherapy in the surgical treatment of gastric cancer in a hospital of the brazilian unified health system

ABSTRACT BACKGROUND: Despite the preference for multimodal treatment for gastric cancer, abandonment of chemotherapy treatment as well as the need for upfront surgery in obstructed patients brings negative impacts on the treatment. The difficulty of accessing treatment in specialized centers in the Brazilian Unified National Health System (SUS) scenario is an aggravating factor. AIMS: To identify advantages, prognostic factors, complications, and neoadjuvant and adjuvant therapies survival in gastric cancer treatment in SUS setting. METHODS: The retrospective study included 81 patients with gastric adenocarcinoma who underwent treatment according to INT0116 trial (adjuvant chemoradiotherapy), CLASSIC trial (adjuvant chemotherapy), FLOT4-AIO trial (perioperative chemotherapy), and surgery with curative intention (R0 resection and D2 lymphadenectomy) in a single cancer center between 2015 and 2020. Individuals with other histological types, gastric stump, esophageal cancer, other treatment protocols, and stage Ia or IV were excluded. RESULTS: Patients were grouped into FLOT4-AIO (26 patients), CLASSIC (25 patients), and INT0116 (30 patients). The average age was 61 years old. More than 60% of patients had pathological stage III. The treatment completion rate was 56%. The pathological complete response rate of the FLOT4-AIO group was 7.7%. Among the prognostic factors that impacted overall survival and disease-free survival were alcoholism, early postoperative complications, and anatomopathological status pN2 and pN3. The 3-year overall survival rate was 64.9%, with the CLASSIC subgroup having the best survival (79.8%). CONCLUSIONS: The treatment strategy for gastric cancer varies according to the need for initial surgery. The CLASSIC subgroup had better overall survival and disease-free survival. The INT0116 regimen also protected against mortality, but not with statistical significance. Although FLOT4-AIO is the preferred treatment, the difficulty in carrying out neoadjuvant treatment in SUS scenario had a negative impact on the results due to the criticality of food intake and worse treatment tolerance.

RESUMO RACIONAL: Apesar da preferência pelo tratamento multimodal para o câncer gástrico, o abandono do tratamento quimioterápico bem como a necessidade de cirurgia "upfront" em pacientes obstruídos traz impactos negativos para o tratamento. A dificuldade de acesso ao tratamento em centros especializados no Sistema Único de Saúde (SUS) é um agravante. OBJETIVOS: Identificar vantagens, fatores prognósticos, complicações e sobrevida de terapias neoadjuvantes e adjuvantes no tratamento do câncer gástrico no cenário do SUS. MÉTODOS: Estudo retrospectivo incluindo 81 pacientes com adenocarcinoma gástrico submetidos a tratamento segundo os protocolos INT0116 (quimiorradioterapia adjuvante), CLASSIC (quimioterapia adjuvante), FLOT4-AIO (quimioterapia perioperatória) e cirurgia com intuito curativo (ressecção R0 e linfadenectomia D2) em um único centro oncológico entre 2015 e 2020. Indivíduos com outros tipos histológicos, coto gástrico, câncer de esôfago, outros protocolos de tratamento e estádio Ia ou IV foram excluídos. RESULTADOS: Os pacientes foram distribuídos em: FLOT4-AIO (26 pacientes), CLASSIC (25 pacientes) e INT0116 (30 pacientes). A média de idade foi 61 anos. Mais de 60% dos pacientes apresentaram estádio III patológico. A taxa de completude do tratamento foi 56%. A taxa de resposta patológica completa do grupo FLOT4-AIO foi 7,7%. Dentre os fatores prognósticos que impactaram a sobrevida global e sobrevida livre de doença tivemos etilismo, complicações pós-operatórias precoces, status anatomopatológico pN2 e pN3. A taxa de sobrevida global em 3 anos foi 64,9% sendo o subgrupo CLASSIC com melhor sobrevida (79,8%). CONCLUSÕES: A estratégia de tratamento do câncer gástrico varia de acordo com a necessidade de cirurgia inicial. O subgrupo CLASSIC apresentou melhor sobrevida global e sobrevida livre de doença. O esquema INT0116 também protegeu contra a mortalidade, mas não com significância estatística. Apesar do FLOT4-AIO ser o tratamento de escolha, a dificuldade na realização da neoadjuvância no âmbito do SUS impactou negativamente nos resultados devido à criticidade da ingesta alimentar e à pior tolerância ao tratamento.

Prognostic factors for local recurrence in patients with rectal cancer submitted to neoadjuvant chemoradiotherapy and total mesorectal excision

Abstract Prognostic factors for local recurrence in patients with rectal cancer submitted to neoadjuvant chemoradiotherapy and total mesorectal excision. Background: The standard curative treatment for locally advanced rectal cancer of the middle and lower thirds is long-course chemoradiotherapy followed by total mesorectal excision. Purpose: To evaluate the prognostic factors associated with local recurrence in patients with rectal cancer submitted to neoadjuvant chemoradiotherapy and total mesorectal excision. Methods: Retrospective study including patients with rectal cancer T3-4N0M0 or T (any)N + M0 located within 10 cm from the anal border, or patients with T2N0M0 located within 5 cm, treated by long course chemoradio-therapy followed by total mesorectal excision with curative intent. Clinical, demographic, radiologic, surgical, and anatomopathological data were collected. Local recurrence was estimated using the Kaplan-Meier function, and risk was estimated according to each characteristic using univariate and multivariate analyses. Results: 270 patients were included, 57.8% male and mean age 61.7 (30‒88) years. At initial staging, 6.7% of patients were stage I, 21.5% stage II, and 71.8% stage III. Open surgery was performed in 65.2%, with sphincter preservation in 78.1%. Mortality within 30 postoperative days was 0.7%. After 49.4 (0.5‒86.1) months of median follow-up, overall and local recurrences were 26.3% and 5.9%. On multivariate analyses, local recurrence was associated with involvement of the mesorectal fascia on restaging MRI (HR = 9.11, p = 0.001) and with pathologic involvement of radial surgical margin (HR = 8.19, p < 0.001). Conclusion: Local recurrence of rectal cancer treated with long-course chemoradiation and total mesorectal excision is low and is associated with pathologic involvement of the radial surgical margin and can be predicted on restaging MRI.

Paclitaxel liposome, cisplatin and 5-fluorouracil-based induction chemotherapy followed by de-escalated intensity-modulated radiotherapy with concurrent cisplatin in stage IVA-IVB childhood nasopharyngeal carcinoma in endemic area: a phase II, single-arm trial.

Background: Previous studies demonstrated that induction chemotherapy (IC) followed by de-escalated chemoradiotherapy adapted to tumor response was effective in treating childhood nasopharyngeal carcinoma (NPC), but the toxicity profile of this treatment strategy, and whether childhood patients with advanced stages can obtain enough benefits from it requires further investigation. Methods: We conducted a single-center phase II trial (NCT03020329). All participants received 3 cycles of paclitaxel liposome, cisplatin and 5-fluorouracil (TPF)-based IC. Patients who showed complete or partial response received de-escalated radiotherapy of 60 Gy with 3 cycles of concurrent cisplatin, and those who showed stable or progressive disease received standard-dose radiotherapy of 70 Gy with concurrent cisplatin. The primary endpoint was the complete response (CR) rate at the end of concurrent chemoradiotherapy (CCRT). Findings: From November 2016 to March 2021, 44 patients were recruited in the cohort. The CR rate was 80% (35/44, 95% CI, 65-90) of the whole cohort. All patients achieved CR 3 months after CCRT. By the last follow-up, the 3-year progression-free survival and overall survival were 91% (95% CI, 82-99) and 100% respectively. Dry mouth was the most common late toxicity, with an incidence of 41% (18/44), followed by skin fibrosis and hearing impairment. No patient suffered from severe late toxicity and growth retardation. Interpretation: Our results proved the efficacy and safety of TPF regimen followed by de-escalated radiotherapy with concurrent cisplatin in treating stage IVa-b childhood NPC patients. Funding: A full list of funding bodies that contributed to this study can be found in the Acknowledgements section.

Carcinoma escamoso de nasofaringe localmente avanzado: actualización en el manejo y rol de la quimioterapia de inducción

El carcinoma escamoso de nasofaringe es responsable del 0,7% del total de tumores malignos a nivel mundial, siendo la mayor incidencia vista en la población del sur de china y sudeste asiático. El tratamiento estándar para la enfermedad localmente avanzada consiste en la combinación de radioterapia y quimioterapia en diferentes secuencias. Dentro de ellas, la quimioterapia de inducción seguida de radio quimioterapia concomitante ha demostrado durante los últimos años ser una opción terapéutica estándar con altas tasas de control locorregional y sobrevida global. El presente trabajo tiene como objetivo revisar la evidencia actual relacionada al tratamiento del cáncer de nasofaringe con quimioterapia de inducción y radio quimioterapia, su efectividad y los aspectos técnicos para su aplicabilidad.

Squamous cell carcinoma of the nasopharynx is responsible for 0.7% of all malignant tumors worldwide, with the highest incidence in the population of southern China and Southeast Asia. The standard treatment for locally advanced disease consists of a combination of radiotherapy and chemotherapy in different schedules. Among them, induction chemotherapy followed by concomitant radio-chemotherapy has shown in recent years to be a standard therapeutic option with high rates of locoregional control and overall survival. This paper aims to review the current evidence related to treatment with induction chemotherapy and subsequent radio-chemotherapy in nasopharyngeal cancer, its effectiveness, and the technical aspects of its applicability.

Morbidity of adjuvant treatment in early cervical cancer: a retrospective cohort study in a Latin American center.

Background: Radical hysterectomy with pelvic lymph node assessment is the standard of treatment in early cervical cancer. Adjuvant radiotherapy or chemoradiotherapy are offered to patients with risk factors for recurrence. The objective of this study was to compare the incidence of severe (> G3) early or late morbidity related to treatment in patients with cervical cancer undergoing radical surgery with/without adjuvant treatment in a Latin American center. Materials and methods: Retrospective cohort study of patients diagnosed with cervical cancer stage IA1 to IB1. Complications were evaluated according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. The cumulative incidence of severe morbidity was estimated. Risk ratios (RR) were calculated to determine the factors associated with morbidity. Results: 239 patients were included. 133 (55.6%) received only radical surgical management and 106 (44.4%) adjuvant treatment. The incidence of early morbidity was 18.8% [95% confidence interval (CI): 12.6% to 26.5%] in the group without adjuvant treatment versus 21.7% (95% CI: 14.3% to 30.8%) in the adjuvant treatment group (p = 0.58). Late morbidity was 3% (95% CI: 1% to 7.5%) and 8.5% (95% CI: 4% to 15.5%), respectively (p = 0.063). No statistically significant differences regarding grade ≥ 3 morbidity between the groups was found (2.3% vs. 5.7%, p = 0.289). Complications during surgery is the only factor associated with postoperative morbidity related to treatment (RR = 4.1) (95% CI: 3% to 5.7%). Conclusion: In our study, the addition of adjuvant treatment for early cervical cancer patients who underwent radical surgery did not increase the incidence of severe early or late morbidity.

Chemo-radiotherapy with 177Lu-PLGA(RGF)-CXCR4L for the targeted treatment of colorectal cancer.

Introduction: More than 1.9 million new cases of colorectal cancer and 935,000 deaths were estimated to have occurred worldwide in 2020. Therapies for metastatic colorectal cancer include cytotoxic chemotherapy and targeted therapies in multiple lines of treatment. Nevertheless, the optimal use of these agents has not yet been resolved. Regorafenib (RGF) is an Food and Drug Administration (FDA)-authorized multikinase inhibitor indicated for patients with metastatic colorectal cancer, non-responding to priority lines of chemotherapy and immunotherapy. Nanoparticles have been used in specific applications, such as site-specific drug delivery systems, cancer therapy, and clinical bioanalytical diagnostics. C-X-C Chemokine receptor type 4 (CXCR4) is the most widely-expressed chemokine receptor in more than 23 human cancer types, including colorectal cancer. This research aimed to synthesize and preclinically evaluate a targeted nanosystem for colorectal cancer chemo-radiotherapy using RGF encapsulated in Poly(D,L-lactic-co-glycolic acid) (PLGA) nanoparticles coated with a CXCR4 ligand (CXCR4L) and 177Lu as a therapeutic ß-emitter. Methods: Empty PLGA and PLGA(RGF) nanoparticles were prepared using the microfluidic method, followed by the DOTA and CXCR4L functionalization and nanoparticle radiolabeling with 177Lu. The final nanosystem gave a particle size of 280 nm with a polydispersity index of 0.347. In vitro and in vivo toxicity effects were assessed using the HCT116 colorectal cancer cell line. Results: 177Lu-PLGA(RGF)-CXCR4L nanoparticles decreased cell viability and proliferation by inhibiting Erk and Akt phosphorylation and promoting apoptosis. Moreover, in vivo administration of 177Lu-PLGA(RGF)-CXCR4L significantly reduced tumor growth in an HCT116 colorectal cancer xenograft model. The biokinetic profile showed hepatic and renal elimination. Discussion: Data obtained in this research justify additional preclinical safety trials and the clinical evaluation of 177Lu-PLGA(RGF)-CXCR4L as a potential combined treatment of colorectal cancer.

The Role of Probe-Based Confocal Laser Endomicroscopy (pCLE) in the Diagnosis of Sustained Clinical Complete Response Under Watch-and-Wait Strategy After Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Adenocarcinoma: a Score Validation.

BACKGROUND: Watch-and-wait strategy has been increasingly accepted for patients with clinical complete response (cCR) after multimodal treatment for locally advanced rectal adenocarcinoma. Close follow-up is essential to the early detection of local regrowth. It was previously demonstrated that probe-based confocal laser endomicroscopy (pCLE) scoring using the combination of epithelial and vascular features might improve the diagnostic accuracy of cCR. AIM: To validate the pCLE scoring system in the assessment of patients with cCR after neoadjuvant chemoradiotherapy (nCRxt) for advanced rectal adenocarcinoma. METHODS: Digital rectal examination, pelvic magnetic resonance imaging (MRI), and pCLE were performed in 43 patients with cCR, who presented either a scar (N = 33; 76.7%) or a small ulcer with no signs of tumor, and/or biopsy negative for malignancy (N = 10; 23.3%). RESULTS: Twenty-five (58.1%) patients were men, and the mean age was 58.4 years. During the follow-up, 12/43 (27.9%) patients presented local regrowth and underwent salvage surgery. There was an association between pCLE diagnostic scoring and final histological report (for patients who underwent surgical resection) or final diagnosis at the latest follow-up (p = 0.0001), while this association was not observed with MRI (p = 0.49). pCLE sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 66.7%, 93.5%, 80%, 88.9%, and 86%, respectively. MRI sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 66.7%, 48.4%, 66.7%, 78.9%, and 53.5%, respectively. CONCLUSIONS: pCLE scoring system based on epithelial and vascular features improved the diagnosis of sustained cCR and might be recommended during follow-up. pCLE might add some valuable contribution for identifying local regrowth. Trial Registration This protocol was registered at the Clinical Trials (ClinicalTrials.gov identifier NCT02284802).

Treatment outcomes of alternating chemoradiotherapy for nasopharyngeal carcinoma: a single-center safety and efficacy study

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