PERIOPERATIVE CHEMOTHERAPY, ADJUVANT CHEMOTHERAPY AND ADJUVANT CHEMORADIOTHERAPY IN THE SURGICAL TREATMENT OF GASTRIC CANCER IN A HOSPITAL OF THE BRAZILIAN UNIFIED HEALTH SYSTEM.

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.

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).

Argon Beam Coagulation as an Adjuvant for Extended Curettage for Giant Cell Tumors of the Bone: A Study of 50 Cases / Coagulação por plasma de argônio como adjuvante à curetagem estendida em tumores de células gigantes do osso: Um estudo de 50 casos

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.

Prognosis of Mesorectal Tumor Deposits in Patients with Rectal Cancer Treated with Neoadjuvant Chemoradiotherapy and Total Mesorectal Excision.

BACKGROUND: Tumor deposits (TDs) are associated with adverse prognostic factors and decreased survival in colon cancer. However, there is no information of their survival impact in rectal cancer with neoadjuvant chemoradiotherapy (n-CRT). METHODS: Retrospective study in 223 patients with rectal cancer with n-CRT. A survival analysis of factors associated with decreased overall survival (OS) including TDs was performed. RESULTS: From 223 patients, 131 (58.7%) were men, mean age 59.8 (± 13.06) years, and 42 (18.8%) of them revealed TDs. Survival analysis of TDs showed no association with mortality. Factors associated with decreased 5-year OS were the histologic grade (p = 0.42), perineural invasion (p = 0.001), and mesorectal quality (p = 0.067). Perineural invasion (HR = 2.335, 95% CI = 1.198-4.552) remained as independent factor in the multivariate analysis. CONCLUSIONS: TDs were not associated with mortality in rectal cancer patients treated with n-CRT. Factors associated with decreased survival were inadequate mesorectal quality and perineural invasion.

Oncological outcomes from surgical vs. non-surgical treatments for advanced hypopharyngeal squamous cell carcinoma: a surveillance, epidemiology, and end results-based study.

OBJECTIVE: Patients with advanced hypopharyngeal squamous cell carcinomas (HSCCs) have poor prognoses. The use of surgical or non-surgical treatments for these patients remains a topic of debate. This study compared survival following surgical and non-surgical treatments of patients with advanced HSCC based on the Surveillance, Epidemiology and End Results (SEER) database. METHODS: Patients diagnosed with hypopharyngeal cancer from 2004 to 2018 were identified from the SEER database. Patients were divided into non-surgical group and surgical group, and patients in the surgical group were further divided into three groups: surgery-only, surgery with adjuvant radiation therapy and surgery with adjuvant chemoradiation therapy. The primary endpoint was overall survival (OS), and the secondary outcome was cancer-specific survival (CSS). Outcomes were analyzed using Kaplan-Meier analysis. A multivariate Cox regression analysis was also used to identify independent prognostic factors. RESULTS: The records of 1568 eligible patients with stage III or IV HSCC were examined. Receipt of surgery was associated with a longer OS [hazard ratio (HR) = 0.47, 95% confidence interval (CI): 0.4-0.56] and a longer CSS (HR = 0.47, 95% CI: 0.38-0.57) after adjusting for age, sex, race, tumor site, tumor size, tumor grade, TNM stage, AJCC stage, number of carcinomas, prior cancer, receipt of radiotherapy, and receipt of chemotherapy. The results for OS were similar in an exploratory analysis of different patient subgroups. CONCLUSION: Among patients with advanced HSCC in the SEER database, treatment with surgery was associated with longer OS and CSS than treatment with a non-surgical modality.

Phase II Randomized Trial of Transoral Surgery and Low-Dose Intensity Modulated Radiation Therapy in Resectable p16+ Locally Advanced Oropharynx Cancer: An ECOG-ACRIN Cancer Research Group Trial (E3311).

PURPOSE: Definitive or postoperative chemoradiation (CRT) is curative for human papillomavirus-associated (HPV+) oropharynx cancer (OPC) but induces significant toxicity. As a deintensification strategy, we studied primary transoral surgery (TOS) and reduced postoperative radiation therapy (RT) in intermediate-risk HPV+ OPC. METHODS: E3311 is a phase II randomized trial of reduced- or standard-dose postoperative RT for resected stage III-IVa (American Joint Committee on Cancer-seventh edition) HPV+ OPC, determined by pathologic parameters. Primary goals were feasibility of prospective multi-institutional study of TOS for HPV+ OPC, and oncologic efficacy (2-year progression-free survival) of TOS and adjuvant therapy in intermediate-risk patients after resection. TOS plus 50 Gy was considered promising if the lower limit of the exact 90% binomial confidence intervals exceeded 85%. Quality of life and swallowing were measured by functional assessment of cancer therapy-head and neck and MD Anderson Dysphagia Index. RESULTS: Credentialed surgeons performed TOS for 495 patients. Eligible and treated patients were assigned as follows: arm A (low risk, n = 38) enrolled 11%, intermediate risk arms B (50 Gy, n = 100) or C (60 Gy, n = 108) randomly allocated 58%, and arm D (high risk, n = 113) enrolled 31%. With a median 35.2-month follow-up for 359 evaluable (eligible and treated) patients, 2-year progression-free survival Kaplan-Meier estimate is 96.9% (90% CI, 91.9 to 100) for arm A (observation), 94.9% (90% CI, 91.3 to 98.6]) for arm B (50 Gy), 96.0% (90% CI, 92.8 to 99.3) for arm C (60 Gy), and 90.7% (90% CI, 86.2 to 95.4) for arm D (66 Gy plus weekly cisplatin). Treatment arm distribution and oncologic outcome for ineligible or step 2 untreated patients (n = 136) mirrored the 359 evaluable patients. Exploratory comparison of functional assessment of cancer therapy-head and neck total scores between arms B and C is presented. CONCLUSION: Primary TOS and reduced postoperative RT result in outstanding oncologic outcome and favorable functional outcomes in intermediate-risk HPV+ OPC.

Cytotoxic T-lymphocyte-associated protein 4 in gastric cancer: Prognosis and association with PD-L1 expression.

BACKGROUND: Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) is one of the most studied immune checkpoint in gastric cancer (GC). However, the prognostic role of CTLA-4 expression in GC is poorly described. This study aimed to evaluate CTLA-4 expression in GC and its impact on survival, including patients treated with standard platinum-based chemotherapy (CMT), and association with PD-L1 expression. METHODS: All GC patients who underwent D2-gastrectomy were investigated retrospectively. Tumor samples were examined for CTLA-4 and PD-L1 by immunohistochemistry. Tumor-infiltrating inflammatory cells, including CD4 + and CD8 + , were also examined. RESULTS: Among the 284 GC patients included, 159 (56%) were CTLA-4 positive and the remaining 125 (44%) were classified as negative. CTLA-4 positive GC was associated with increased inflammatory cell infiltration (p < 0.001), high CD8 + T cells (p = 0.016) and PD-L1 expression (p = 0.026). Considering GC referred for treatment, CTLA-4 negative patients who received CMT had a significant improvement in disease-free survival compared to untreated CLTA-4 negative (p = 0.028). In multivariate analysis, GC positive for both CTLA-4 and PD-L1 had a prognostic impact on survival. CONCLUSION: CTLA-4 positive was associated with PD-L1 expression and a high tumor-infiltrating CD8 + T cells. Accordingly, positivity for both CTLA-4 and PD-L1 was an independent factor associated to better survival in GC patients.

SEOM clinical guidelines for the treatment of head and neck cancer (2020).

Head and neck cancers (HNC) are defined as malignant tumours located in the upper aerodigestive tract and represents 5% of oncologic cases in adults in Spain. More than 90% of these tumours have squamous histology. In an effort to incorporate evidence obtained since 2017 publication, the Spanish Society of Medical Oncology (SEOM) presents an update of the squamous cell HNC diagnosis and treatment guideline. Most relevant diagnostic and therapeutic changes from the last guideline have been updated: introduction of sentinel node biopsy in early oral/oropharyngeal cancer treated with surgery, concomitant radiotherapy with weekly cisplatin 40 mg/m2 in the adjuvant setting, new approaches for HPV-related oropharyngeal cancer and new treatments with immune-checkpoint inhibitors in recurrent/metastatic disease.

Predictors of pathological response and clinical outcome following chemoradiation for locally advanced rectal cancer - a systematic review / Preditores de resposta patológica e de outcome clinico após quimioradioterapia neoadjuvante para cancro do reto localmente avançado - uma revisão sistemática

Abstract Background: Colorectal cancer is one of the most common types of cancer and is associated with a high lethality rate. Treatment is multidisciplinary, and neoadjuvant chemoradiation is recommended in locally advanced rectal cancer. About 15% of patients answer favorably to neoadjuvant chemoradiation, so it is important to determine the predictors of response. Objective: To review the results of studies that analyzes the predictors of complete pathological response to neoadjuvant chemoradiation in patients with locally advanced rectal cancer. Search methods: We searched for eligible articles in data bases Pubmed and Scopus, between the 12th and the 20th of March 2020. The following key words were used: "predictors of response", "chemoradiation" and "locally advanced rectal cancer". Selection criteria: Inclusion criteria: Studies including patients with locally advanced rectal cancer, patients receiving neoadjuvant chemoradiation as treatment, studies including predictors of response to neodjuvant chemoradiation, overall survival as an outcome and regarding language restrictions, only articles in English were accepted, only studies published until the 31st of December 2019 were accepted. Main results: Fourteen studies fulfilled the inclusion criteria. Thirteen are cohort studies and one is a clinical trial. Four groups of predictors were defined: blood markers, tumors, histopathological and patients' characteristics. Author's conclusions: During the analysis of the articles, there were several predictors identified as potential candidates for clinical practice, such as high pre neoadjuvant chemoradiation Carcinoembryonic Antigen levels and small post neoadjuvant chemoradiation tumor size. Nevertheless, it is difficult to make definitive conclusions about the most reliable predictors. That is why it is crucial to initiate further studies with standardized cut-off values and a methodology homogenization.

Resumo Introdução: O cancro colorretal é um dos cancros mais prevalentes em Portugal e tem associada uma alta taxa de letalidade. Atualmente, o tratamento é multidisciplinar, e a quimioradioterapia neoadjuvante está indicada no Cancro do Reto Localmente Avançado. Sabe-se que cerca de 15% dos doentes responde favoravelmente à quimioradioterapia neoadjuvante, sendo por isso importante determinar quais os preditores de resposta a este tipo de tratamento. Objetivo: Rever os resultados dos estudos que analisam os preditores de resposta completa à quimioradioterapia em pacientes com Cancro do Reto Localmente Avançado. Métodos de pesquisa: Pesquisamos artigos elegíveis nos bancos de dados Pubmed e Scopus, desde o dia 12 a 20 de Março de 2020. Foram utilizadas as seguintes palavras chave: "preditores de resposta", "quimioradioterapia neoadjuvante" e "Cancro do Reto Localmente Avançado". Critérios de seleção: Critérios de inclusão: Estudos que incluam pacientes com Cancro do Reto Localmente Avançad, pacientes sujeitos a quimioradioterapia neoadjuvante, preditores de resposta à quimioradioterapia, que avaliem a sobrevivência como outcome, escritos em inglês e publicados até dia 31 de Dezembro de 2019. Resultados principais: Catorze estudos preencheram os critérios de inclusão. De todos os artigos, treze são Cohort e um é Clinical Trial. Foram definidos quatro grupos de preditores: marcadores de sangue e caraterísticas do tumor, histopatológicas e dos pacientes. Conclusões dos autores: Durante a análise dos artigos, foram identificados vários preditores como potenciais candidates para a prática clínica, tais como o valor elevado de antigénio carcinoembrionário pré- quimioradioneoaajuvância e tamanho reduzido. Contudo, é arriscado elaborar conclusões concretas relativamente aos preditores mais confiáveis. Por isso, é crucial iniciar novos estudos com valores de cut-off estandardizados e métodos com maior homogeneidade.

Do We Have to Treat All T3 Rectal Cancer the Same Way?

Chemoradiotherapy (CRT) followed by surgery is the recommended approach in the last years for stage II and III rectal cancer with the intention to decrease the risk of local recurrence. However, fewer patients benefit from this strategy in terms of overall survival and long-term adverse outcomes because T3 rectal cancer has a broad range of prognosis, as shown by recent publications. Many patients with cT3 rectal cancer have a substantial risk of overtreatment with long-term toxicity related to radiotherapy that could be avoided in a subset group of cT3 tumors with good prognosis. These findings raised the question of whether all cT3 rectal cancer should receive preoperative radiotherapy and if a selected cT3 subgroup could be treated by surgery alone. This review addresses the rationale of selecting good prognosis cT3 rectal cancer for surgery alone and analyzes the data to support this recommendation.

The importance of adjuvant treatment and primary anatomical site in head and neck basaloid squamous cell carcinoma survival: an analysis of the National Cancer Database.

PURPOSE: Basaloid squamous cell carcinoma (BSCC) of the head and neck is an aggressive and highly malignant variant of squamous cell carcinoma that accounts for 2% of head and neck cancers. Previous studies have not analyzed the significance of adjuvant chemoradiation and anatomical site within BSCC subtype and its impact on survival. METHODS: A cohort of 1999 patients with BSCC of the head and neck was formed from the National Cancer Database and analyzed with descriptive studies, median survival and 5- and 10-year survival. A multivariable Cox hazard regression was performed to determine the prognostic significance of anatomical site and adjuvant therapy. RESULTS: The most common primary anatomical site was the oropharynx (71.9%) followed by oral cavity (11.5%), larynx (10.1%), hypopharynx (3.5%), esophagus (1.9%), and nasopharynx (1.1%). The presence of metastasis increased the risk of mortality (HR = 2.14; 95% CI 1.40-3.26). Tumors localized to the oropharynx demonstrated better survival compared to all sites except nasopharynx, including the oral cavity (HR = 2.45; 95% CI 1.83-3.29), hypopharynx (HR = 2.58; 95% CI:1.64-4.05), and larynx (HR = 2.89; 95% CI:2.25-3.73). Adjuvant chemoradiation (HR = 0.36; 95% CI 0.23-0.58) and adjuvant radiation (HR = 0.38; 95% CI 0.23-0.64) had better survival outcomes compared to adjuvant chemotherapy. Patients with microscopic margins had better survival outcomes when compared to no surgery (HR = 0.38, 98% Cl 0.23-0.64) while there were no better survival outcomes of patients with macroscopic margins compared to no surgery. CONCLUSION: This study illustrated that tumors in the oropharynx, lower age, adjuvant chemoradiation and radiation, and microscopic margins were associated with greater survival.

What is the impact of radical hysterectomy on endometrial cancer with cervical involvement?

BACKGROUND: When endometrial carcinoma invades the cervical stroma, overall survival and disease-free survival decrease. However, it is still controversial whether patients in suspected stage II should be treated with radical hysterectomy. The goal of this study is to describe the role of radical hysterectomy in patients with endometrial carcinoma and cervical involvement. METHODS: This was a retrospective cohort study were a total of 239 patients with endometrial carcinoma with cervical involvement from Mexico City's National Cancer Institute were divided according to the type of hysterectomy, and the outcomes were compared using statistical analysis. RESULTS: The 5-year overall survival was 75.76% for the simple hysterectomy group and 89.19% for the radical hysterectomy group, without achieving statistical significance. The 5-year disease-free survival was 72.95% for the simple hysterectomy group and 64.31% for the radical hysterectomy group, without achieving statistical significance. Radicality was associated with longer surgical times, intraoperative complications, and bleeding over 500 ml. CONCLUSIONS: In patients with endometrial carcinoma with cervical involvement, radical hysterectomy does not improve prognosis or alter adjuvant therapy.

Predictive factors for tumour response after the neoadjuvant-treatment of rectal adenocarcinoma / Fatores preditivos de resposta tumoral após tratamento neoadjuvante de adenocarcinoma retal

ABSTRACT Purpose Standard of care for locally advanced rectal cancer is neoadjuvant chemoradiotherapy followed by surgery. This study identified predictive factors for tumour response in our series. Patients and methods Between January 2005 and December 2018, 292 patients with locally advanced rectal cancer treated by preoperative chemo-radiation before surgery were retrospectively analyzed. The radiation dose was 50.4 Gy with fluoropyrimidine-based chemotherapy regimens. Patients-tumour and treatment-factors were tested for influence on tumour down staging and regression grade using Mandard scoring system on surgical specimens (TRG). Results Median age was 69 years (range 39-87); 33.9% of patients was Stage II and 54.5% Stage IIIB. Tumour down staging occurred in 211 patients (73%), including 63 patients (21.6%) with ypT0 (documented T0 at surgery) and 148 patients (50.7%) with a satisfactory tumour regression grade defined as TRG2­3. Upper rectal tumours were identified to predictive factors for pathologic complete response by univariate analysis (p = 0.002). TRG1­3 was associated with intervals from chemo-radiation to surgery (p = 0.004); TRG1­3 rates were higher with longer intervals: 1.71% in ≤ 5 weeks, 23.63% in 6-8 weeks and 46.9% in ≥ 9 weeks; and PTV 50.4 ≥ 800cc (p = 0.06); 3 and 5 years survivals were 85% and 90% for the group as a whole. Among ypT0 cases, the overall survival was 91.1% without significantly different (p = 0.25) compared with the remaining group, 87.2%. Among ypT0 cases, the relapse-free survival was 94.5%, with significantly different (p = 0.03) compared with the remaining group 78.2%. There were no treatment-associated fatalities. Thirty-two patients (10.96%) experienced Grade III/IV toxicities (proctitis, ephitelitis and neutropenia). Conclusions Tumour localization was identified as predictive factors of pathologic complete response for locally advanced rectal cancer treated with preoperative chemo-radiation. Upper rectal tumours are more likely to develop complete responses. Delay in surgery was identified as a favorable predictive factor for TRG1­3. The relapse-free survival in pathologic complete response group was higher compared with non-pathologic complete response.

RESUMO Objetivo O tratamento padrão para o câncer retal localmente avançado é a quimiorradioterapia neoadjuvante, seguida de cirurgia. Este estudo identificou fatores preditivos de resposta tumoral em nossa série. Pacientes e métodos Entre janeiro de 2005 e dezembro de 2018, 292 pacientes com câncer retal localmente avançado, tratados com quimiorradiação pré-operatória, foram retrospectivamente analisados. O tratamento quimioterápico foi à base de fluoropirimidina e a dose de radiação foi de 50,4 Gy. Os tumores dos pacientes e os fatores do tratamento foram testados quanto à influência no estadiamento do tumor e no grau de regressão usando o sistema de classificação de Mandard em espécimes cirúrgicos (TRG). Resultados A mediana das idades foi 69 anos (variação de 39 a 87); 33,9% dos pacientes estavam no estágio II e 54,5% no estágio IIIB. O estadiamento do tumor ocorreu em 211 pacientes (73%), incluindo 63 pacientes (21,6%) com ypT0 (T0 documentado na cirurgia) e 148 pacientes (50,7%) com grau satisfatório de regressão do tumor, definido como TRG1­3. Os tumores retais superiores foram identificados como fatores preditivos de resposta patológica completa por análise univariada p = 0,002. TRG1­3 foi associado aos intervalos entre a quimioterapia e a cirurgia p = 0,004; As taxas de TRG1­3 foram maiores com intervalos mais longos: 1,71% em ≤ 5 semanas, 23,63% em 6-8 semanas e 46,9% em ≥ 9 semanas; e PTV 50,4 ≥ 800cc (p = 0,06); as sobrevidas de 3 e 5 anos foram de 85% e 90% para o grupo em geral. Entre os casos de ypT0, a sobrevida global foi de 91,1%, sem diferença significativa (p = 0,25) na comparação com o grupo restante (87,2%). Entre os casos de ypT0, a sobrevida livre de recidiva foi de 94,5%, com diferença significativa (p = 0,03) na comparação com o grupo restante (78,2%). Não houve fatalidades associadas ao tratamento. Trinta e dois pacientes (10,96%) apresentaram toxicidade de grau III/IV (proctite, efitelite e neutropenia). Conclusões A localização do tumor foi identificada como fator preditivo de resposta patológica completa para o câncer retal localmente avançado tratado com quimiorradiação pré-operatória. Os tumores retais superiores têm mais probabilidade de desenvolver respostas completas. O atraso da cirurgia foi identificado como um fator preditivo favorável para o TRG1­3. A sobrevida livre de recidiva no grupo com resposta patológica completa à quimiorradioterapia pré-operatória foi maior comparado ao grupo com resposta patológica incompleta.

Adjuvant therapy for true ampullary cancer: a systematic review.

BACKGROUND: Given the lack of evidence on the best adjuvant approach, this review closely examines optimal adjuvant management for resected true ampullary cancer and its histological subtypes. MATERIALS AND METHODS: A comprehensive literature search of PubMed was performed to identify studies on resected true ampullary cancers, published between January 2010 and December 2018. Data including the use of radiation, chemotherapy or chemoradiation and the outcomes were extracted. RESULTS: A total of 116 records were identified, of which 65 screened were selected. Finally, nine studies were included. Only two of the studies reported separately the outcomes of pancreatobiliary and intestinal subtypes. Patients in the selected studies were treated with a pancreaticoduodenectomy with negative margins. Patients treated with adjuvant therapy were more likely to be pT3-4 and have positive nodes; median survival ranged from 30 to 47 months. A significant benefit for adjuvant treatment was observed in four of the studies, restricted to patients at stage IIB or higher. Likewise, patients with positive nodes may have a longer median survival with adjuvant chemoradiation compared to observation. CONCLUSIONS: The present review suggests a benefit for adjuvant treatment for patients with locally advanced tumors. Randomized trials are needed to ascertain the topic, as well as studies reporting toxicity and quality of life of resected true ampullary cancer patients.

Prognostic factors associated with survival in a large cohort of gastric cancer patients resected over a decade at a single Italian center: the Cremona experience.

BACKGROUND: Incidence of gastric cancer (GC) shows different distribution in Italy, with higher incidence in the north and center. We retrospectively analyzed the clinical data of patients resected at the Hospital of Cremona between January 2007 and December 2016. Available clinical variables were linked with survival to identify possible prognostic factors. MATERIALS AND METHODS: Variables analyzed were age, sex, type of surgery, site, histology, invasion, nodal status, resection margins, grade, HER2 status, Helicobacter pylori infection (neo)adjuvant chemotherapy, adjuvant chemoradiotherapy, neutrophil-to-lymphocyte ratio, number of nodes removed and type of lymphadenectomy. Overall survival (OS) was estimated by the Kaplan-Meier method and differences between groups by the log-rank test. Data on OS were analyzed by Cox regression and the final model was obtained using the step-wise method. RESULTS: 379 patients were considered, out of which 195 were operated from 2007 to 2011 and 184 from 2012 to 2016. Median follow-up was 25.5 months, median OS 31.3 months and time to recurrence 23.2 months. D2 resection rate increased from 36% (period 2007-2011) to 74% in 2012-2016 (p = 0.01) with a higher mean number of nodes collected (20.98 for 2007-2011 and 23.53 for 2012-2016, p = 0.040). Only 37% of patients received a postoperative treatment. At multivariate analysis, variables associated with OS were age (p = 0.002), stage (p < 0.001), resection margins status (p < 0.001), adjuvant chemotherapy (p < 0.010) and tumor location (cardia vs non-cardia) (p = 0.029). CONCLUSIONS: Our analysis shows that completeness of resection and lower stage are strong predictors of long-term survival in GC, providing the rationale for adjuvant and neoadjuvant approaches (chemotherapy, radiotherapy or combined). Cardial GC has worse prognosis compared to distal cancers. TRIAL REGISTRATION NUMBER: Service evaluation number 256, protocol 16821/17, date 05 June 2017.

The efficacy and safety of docetaxel, cisplatin and fluorouracil (TPF)-based induction chemotherapy followed by concurrent chemoradiotherapy for locoregionally advanced nasopharyngeal carcinoma: a meta-analysis.

OBJECTIVES: In recent years, docetaxel, cisplatin and fluorouracil (TPF)-based induction chemotherapy (IC) has been widely applied in the treatment of locoregionally advanced nasopharyngeal carcinoma (LA-NPC). However, it remains unclear whether TPF is the ideal IC regimen. Thus, we carried out a meta-analysis to compare the efficacy and safety of TPF-based IC plus concurrent chemoradiotherapy (CCRT) versus CCRT alone or double-drug-based IC plus CCRT for LA-NPC. METHODS: We systematically searched PubMed, Embase and the Cochrane Library from inception until December 2018. After rigorous screening of all relevant studies that reported the use of TPF-based IC followed by CCRT for patients with LA-NPC, eight studies met the inclusion criteria and were assessed for design and quality. Among them, three articles were classified as having a high risk of bias and were excluded from the meta-analysis. The outcomes, including overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), locoregional failure-free survival (LRFFS) and incidence of adverse events, were pooled with the use of hazard ratio (HR) or odds ratio (OR). Heterogeneity and sensitivity analyses were also carried out. RESULTS: Five trials involving 4223 patients were included in the meta-analysis. Compared to CCRT alone, TPF-based IC plus CCRT significantly improved OS (HR 0.54, 95% confidence interval [CI] 0.35-0.84, P = 0.006), PFS (HR 0.64, 95% CI 0.46-0.88, P = 0.006), LRFFS (HR 0.57, 95% CI 0.34-0.94, P = 0.03), and DMFS (HR 0.58, 95% CI 0.38-0.88, P = 0.01). Moreover, compared to double-drug-based IC plus CCRT, OS (HR 0.74, 95% CI 0.62-0.87, P = 0.0004), PFS (HR 0.76, 95% CI 0.66-0.88, P = 0.0001) and LRFFS (HR 0.75, 95% CI 0.61-0.92, P = 0.006) were also significantly improved by TPF-based IC plus CCRT. Notably, TPF-based IC plus CCRT mainly led to an increased risk of hematologic toxicities, such as leucopenia (OR = 3.20, 95% CI 2.13-4.81, P < 0.0001) and neutropenia (OR = 3.84, 95% CI 0.66-22.36, P = 0.13). However, these were uncomplicated and manageable with growth factor support. CONCLUSIONS: Compared to CCRT alone or double-drug-based IC plus CCRT, TPF-based IC plus CCRT results in better survival outcomes with manageable toxicities. Thus, it is reasonable to recommend the addition of TPF-based IC to CCRT as an excellent choice for patients with LA-NPC.

ADJUVANT CHEMORADIOTHERAPY AFTER SUBTOTAL OR TOTAL GASTRECTOMY AND D2 LIMPHADENECTOMY INCREASES SURVIVAL IN ADVANCED GASTRIC CANCER?

BACKGROUND: The treatment of advanced gastric cancer with curative intent is essentially surgical and chemoradiotherapy is indicated as neo or adjuvant to control the disease and prolong survival. AIM: To assess the survival of patients undergoing subtotal or total gastrectomy with D2 lymphadenectomy followed by adjuvant chemoradiotherapy. METHODS: Were retrospectively analyzed 87 gastrectomized patients with advanced gastric adenocarcinoma, considered stages IB to IIIC and submitted to adjuvant chemoradiotherapy (protocol INT 0116). Tumors of the esophagogastric junction, with peritoneal implants, distant metastases, and those that had a compromised surgical margin or early death after surgery were excluded. They were separated according to the extention of the gastrectomy and analyzed for tumor site and histopathology, lymph node invasion, staging, morbidity and survival. RESULTS: The total number of patients who successfully completed the adjuvant treatment was 45 (51.7%). Those who started treatment and discontinued due to toxicity, tumor-related worsening, or loss of follow-up were 10 (11.5%) and reported as incomplete adjuvant. The number of patients who refused or did not start adjuvant treatment was 33 (48.3%). Subtotal gastrectomy was indicated in 60 (68.9%) and total in 27 (31.1%) and this had a shorter survival. The mean resected lymph nodes was 30.8. Staging and number of lymph nodes affected were predictors of worse survival and the more advanced the tumor. Patients undergoing adjuvant therapy with complete chemoradiotherapy showed a longer survival when compared to those who did it incompletely or underwent exclusive surgery. On the other hand, comparing the T4b (IIIB + IIIC) staging patients who had complete adjuvance with those who underwent the exclusive operation or who did not complete the adjuvant, there was a significant difference in survival. CONCLUSION: Adjuvant chemoradiotherapy presents survival gain for T4b patients undergoing surgical treatment with curative intent.

Colgajo temporal en la reconstrucción de un defecto maxilar por exéresis de carcinoma ameloblástico / Temporalis muscle flap in the reconstruction of a maxillary defect caused by exeresis of ameloblastic carcinoma

RESUMEN Introducción: El carcinoma ameloblástico es una entidad rara que surge como una neoplasia primaria o a partir de un ameloblastoma preexistente. El colgajo de músculo temporal es una opción terapéutica frecuentemente empleada para la reconstrucción del defecto resultante luego de la exéresis quirúrgica. Objetivo: Presentar un caso clínico de restauración estética y funcional mediante reconstrucción con colgajo temporal de un defecto maxilar por exéresis de carcinoma ameloblástico, dada la infrecuente presentación de esta entidad. Caso clínico: Mujer de 49 años de edad, que refiere "una bola" en el paladar de 9 meses de evolución. Al examen físico facial presenta aumento de volumen en región infraorbitaria izquierda. Se realizó una tomografía axial computarizada en la que se constató la presencia de imagen hiperdensa en seno maxilar izquierdo con calcificación en su interior, produciendo lisis del hueso nasal y hueso cigomático infiltrando partes blandas. Se tomó muestra para biopsia que informó tumor de alto grado de malignidad correspondiente a carcinoma ameloblástico. En estudio radiográfico de tórax no se apreció presencia de metástasis pulmonar. Se realizó maxilarectomía de infra y mesoestructura, resección de la lesión con margen oncológico de seguridad y se reconstruyó el defecto palatino con colgajo pediculado del músculo temporal. Se indicó quimio y radioterapia como terapia adyuvante al tratamiento quirúrgico. Se mantuvo el chequeo posoperatorio mostrándose buena evolución clínica y una epitelización secundaria del músculo temporal en el área palatina con restauración de las funciones. Conclusiones: Se presentó un caso clínico de carcinoma ameloblástico, entidad patológica de escasa frecuencia. La cirugía constituyó el pilar de tratamiento utilizado. Una vez realizada la resección quirúrgica se reconstruyó el defecto palatino, utilizándose el colgajo del músculo temporal, opción útil para lograr el restablecimiento de las funciones estéticas y funcionales como la deglución y fonación(AU)

ABSTRACT Introduction: Ameloblastic carcinoma is a rare condition emerging as a primary neoplasm or from a preexisting ameloblastoma. Temporalis muscle flap is a therapeutic option frequently used for reconstruction of the defect resulting from surgical exeresis. Objective: Present a clinical case of esthetic and functional restoration by reconstruction with temporalis muscle flap of a maxillary defect caused by exeresis of an ameloblastic carcinoma. The case is presented because of the infrequent occurrence of this condition. Clinical case: A female 49-year-old patient reports "a lump" in her palate of nine months evolution. Physical examination finds an increase in volume in the left infraorbital region. Computed axial tomography was indicated, which revealed the presence of a hyperdense image in the left maxillary sinus with internal calcification causing lysis of the nasal bone and the zygomatic bone, and infiltrating soft tissue. A sample was taken for biopsy, which reported a tumor with a high degree of malignancy corresponding to ameloblastic carcinoma. Chest radiography did not show the presence of lung metastasis. Infra- and mesostructure maxillectomy was performed, the lesion was removed with a surgical safety margin, and the palatine defect was reconstructed with a pediculated temporalis muscle flap. Chemo- and radiotherapy were indicated as adjuvants to the surgical treatment. Postoperative follow-up found good clinical evolution and secondary epithelization of the temporalis muscle in the palatine area with restoration of functions. Conclusions: A clinical case was presented of ameloblastic carcinoma, a condition with a low frequency of occurrence. Surgery was the basic component of the treatment applied. Once surgical resection was performed, the palatine defect was reconstructed by means of a temporalis muscle flap, a useful option to achieve the restoration of esthetic and biological functions, such as swallowing and speech(AU)

Rectal cancer and chemoradiation in Iraq: systematic review and meta-analysis / Câncer retal e quimiorradioterapia no Iraque: revisão sistemática e metanálise

Abstract Background: Rectal cancer is one of the most common malignant tumors of gastrointestinal tract. Combining chemotherapy with radiotherapy has a sound effect on its management. Objectives: Assessment the patterns of characterizations of rectal cancer. Evaluation of the efficacy, and long-term survival of pre-/ postoperative chemoradiation. Collecting all eligible evidence articles and summarize the results. Methods: By this systematic review and meta-analysis study, we include data of chemoradiation of rectal cancer articles from 2015 until 2019. The research was carried out at Baghdad Medical City oncology centers. Accordance with the PRISMA guidelines, and the Newcastle-Ottawa Scale used. Results: Starting with gender distribution as M:F ratio of 0.94:1.06. Regarding the age, recorded mean ± SD of 48.7 ± 14.2 years. Rectosigmoid represented the most common site as 50(49.5%), and adenocarcinoma was common histopathology as 76(75.2%) of patients, with localized stage in 50(49.5%). The moderate differentiation was most grade as 65(64.4%). The distant from anal verge mostly seen was 5-10 cm in 59(58.4%). The pulmonary was commonest site of metastasis in 11(10.9%). Most patients undergo APR operation, which has done in 41(40.6%). Adjuvant chemoradiation received by 40(39.6%) patients, whereas neoadjuvant chemoradiation gave to 25 patients. A total of 2609 articles from 12 databases met our search strategies. The highest Newcastle-Ottawa score (8) demonstrated in three studies, and median score (7) calculated in five studies. Conclusions: The incidence belonged to 5th and 6th decade of life. Rectosigmoid represented the most common site. Mostly, the 5-10 cm distant of tumor from anal verge was common finding. The pulmonary was most site of metastasis. We concluded the formulation of a novel point that survival benefit found in many pre or postoperative chemoradiation trials in rectal cancer.

Resumo Introdução: O câncer retal é um dos tumores malignos mais comuns do trato gastrointestinal. A combinação de quimioterapia e radioterapia em seu tratamento é eficaz. Objetivos: Avaliar os padrões de caracterização do câncer retal. Avaliar a eficácia e sobrevida a longo prazo em pacientes submetidos a quimiorradioterapia pré- ou pós-operatória. Coletar todos os artigos de evidências qualificados e resumir os resultados. Métodos: Esta revisão sistemática e metanálise incluiu dados de ensaios clínicos randomizados por cluster de 2015 até 2019. A pesquisa foi realizada nos centros de oncologia do Baghdad Medical City. As diretrizes PRISMA e a escala de Newcastle-Ottawa foram utilizadas para avaliar os estudos. Resultados: Quanto à distribuição por sexo, observou-se uma relação homem:mulher de 0,94:1,06. Em relação à idade, a média ± DP foi de 48,7 ± 14,2 anos. O retossigmoide fpo o local mais comum em 50 pacientes (49,5%); a histopatologia mais comum foi adenocarcinoma, observada em 76 pacientes (75,2%), com estágio localizado em 50 (49,5%). Diferenciação moderada foi observada em 65 pacientes (64,4%). A distância da borda anal variou entre 5 e 10 cm em 59 pacientes (58,4%). O pulmão foi o local mais comum de metástase, sendo observado em 11 pacientes (10,9%). A maioria dos pacientes (41 [40,6%]) foi submetida à ressecção abdominoperineal. Um total de 40 pacientes (39,6%) foram submetidos a quimiorradioterapia adjuvante e 25, a quimiorradioterapia neoadjuvante. Na revisão da literatura, foram encontrados 2.609 artigos que atendiam aos critérios de pesquisa utilizados em 12 bancos de dados. Três estudos atingiram o escore máximo na escala de Newcastle-Ottawa (8); cinco estudos atingiram o escore mediano (7). Conclusões: No presente estudo, a maior incidência de câncer retal foi observada entre a quinta e sexta décadas de vida. O retossigmoide foi o sítio tumoral mais comum. A maioria dos tumores estava localizado entre 5 a 10 cm de distância da margem anal. O pulmão foi o local mais importante de metástase. No presente estudo, quimiorradioterapia pré- ou pós-operatória estava relacionada a uma maior sobrevida em casos de câncer retal.