Conventional Adjuvant Chemotherapy Research Articles

Early versus conventional adjuvant chemotherapy in stage III colon cancer: A multicenter, randomized, open-label, phase 3 trial.

Early versus conventional adjuvant chemotherapy in stage III colon cancer: A multicenter, randomized, open-label, phase 3 trial.

Clinicopathological Features and Survival Outcomes of Resected Lung Adenosquamous Carcinoma: Results From a Nationwide Japanese Registry Data

ObjectivesThe objective of this study was to clarify the clinicopathological features and prognostic factors of resected lung adenosquamous carcinoma (ASC) using a nationwide multi-institutional database. MethodsWe retrospectively reviewed the records of 15,542 patients who underwent complete R0 resection for ASC (n = 326), adenocarcinoma (AC, n = 11,820), or squamous cell carcinoma (SC, n = 3396) from a Japanese lung cancer registry in 2010. To reduce the selection bias, an inverse probability of treatment weighting (IPTW) method using a propensity score was implemented. ResultsThe ASC group showed worse recurrence-free and overall survival (RFS and OS) than both the AC and SC groups (5-year OS: 57.5% in ASC, 83.9% in AC [< 0.001], and 62.3% in SC [P = .086]). In multivariate analyses, prognostic factors that affected OS for ASC included male, p-stage II-III, and postoperative complications within 30 days (grade ≥ 3 in the Clavien–Dindo classification). The sensitizing EGFR mutation was detected in 28 (21.5%) of 130 screened patients with ASC, but it did not affect either RFS, OS, or postrecurrence survival. Although more patients in the ASC group received adjuvant chemotherapy compared to the AC and SC groups, both multivariate and IPTW-adjusted analyses did not show positive impact of adjuvant chemotherapy on RFS and OS in ASC. ConclusionsIn this nationwide registry study, lung ASC was more aggressive than both AC and SC. No apparent survival impact of conventional adjuvant chemotherapy prompted us to investigate novel adjuvant strategies to optimize survival outcomes.

Impact of central nervous system metastasis after complete resection of lung adenocarcinomas harboring common EGFR mutation – A real-world database study in Japan: The CReGYT-01 EGFR study

ObjectivesTo clarify the impact of central nervous system (CNS) metastasis on performance status (PS) at relapse, on subsequent treatment(s), and on survival of patients with lung adenocarcinoma harboring common epidermal growth factor receptor (EGFR) mutation. MethodsWe conducted the multicenter real-world database study for patients with radical resections for lung adenocarcinomas between 2015 and 2018 at 21 centers in Japan. EGFR mutational status was examined at each center. ResultsOf 4181 patients enrolled, 1431 underwent complete anatomical resection for lung adenocarcinoma harboring common EGFR mutations. Three-hundred-and-twenty patients experienced disease relapse, and 78 (24%) had CNS metastasis. CNS metastasis was significantly more frequent in patients with conventional adjuvant chemotherapy than those without (30% vs. 20%, P = 0.036). Adjuvant chemotherapy did not significantly improve relapse-free survival at any pathological stage (adjusted hazard ratio for stage IA2–3, IB, and II-III was 1.363, 1.287, and 1.004, respectively). CNS metastasis did not affect PS at relapse. Subsequent treatment, mainly consisting of EGFR-tyrosine kinase inhibitors (TKIs), could be equally given in patients with or without CNS metastasis (96% vs. 94%). Overall survival after relapse was equivalent between patients with and without CNS metastasis. ConclusionThe efficacy of conventional adjuvant chemotherapy may be limited in patients with lung adenocarcinoma harboring EGFR mutations. CNS metastasis is likely to be found in practice before deterioration in PS, and may have little negative impact on compliance with subsequent EGFR-TKIs and survival after relapse. In this era of adjuvant TKI therapy, further prospective observational studies are desirable to elucidate the optimal management of CNS metastasis.

Engineered biomaterial delivery strategies are used to reduce cardiotoxicity in osteosarcoma.

Osteosarcoma (OS) is the most common malignant bone tumor in children and adolescents. Chemotherapy drugs play an integral role in OS treatment. Preoperative neoadjuvant chemotherapy and postoperative conventional adjuvant chemotherapy improve survival in patients with OS. However, the toxic side effects of chemotherapy drugs are unavoidable. Cardiotoxicity is one of the common side effects of chemotherapy drugs that cannot be ignored. Chemotherapy drugs affect the destruction of mitochondrial autophagy and mitochondria-associated proteins to cause a decrease in cardiac ejection fraction and cardiomyocyte necrosis, which in turn causes heart failure and irreversible cardiomyopathy. Biomaterials play an important role in nanomedicine. Biomaterials act as carriers to deliver chemotherapy drugs precisely around tumor cells and continuously release carriers around the tumor. It not only promotes anti-tumor effects but also reduces the cardiotoxicity of chemotherapy drugs. In this paper, we first introduce the mechanism by which chemotherapy drugs commonly used in OS cause cardiotoxicity. Subsequently, we introduce biomaterials for reducing cardiotoxicity in OS chemotherapy. Finally, we prospect biomaterial delivery strategies to reduce cardiotoxicity in OS.

The CIRCULATE Spain study: Circulating tumor DNA based decision for adjuvant treatment in localized colon cancer.

TPS3635 Background: A substantial proportion of colon cancer (CC) patients do not benefit from adjuvant chemotherapy, and almost 40% of them will develop metastases despite initial optimal treatment. We have designed the phase 2 CIRCULATE-SPAIN trial (EudraCT Number: 2021-000507-2) to prove the feasibility of using liquid biopsy detection of minimal residual disease to guide the post-surgical clinical management of localized CC patients. Moreover, it is important to define if conventional versus intensive adjuvant chemotherapy could convert plasma circulating tumor DNA (ctDNA) positive into a ctDNA negative status. Methods: CIRCULATE-SPAIN is a trial to prove the feasibility of using liquid biopsy detection of MRD to guide the post-surgical clinical management of early colon cancer patients. It is a multicenter, randomized, open-label phase II “Single-To-double ARm Transition (START)” study in which patients are firstly enrolled into a single arm (Phase IIa) study expandable to a randomized double arm (Phase IIb). The CIRCULATE-SPAIN trial involves two primary endpoints, one for the Phase IIa and a second one for the Phase IIb. The primary objective for Phase IIa is to analyze the potential effect of FOLFOXIRI as an intensive adjuvant treatment for ctDNA clearance as a surrogate biomarker of treatment efficacy. Only if the pre-fixed result of 14 out of 40 patients achieves ctDNA clearance, the trial will be expanded to a phase IIb in which patients will be enrolled to randomly receive intensive adjuvant treatment (FOLFOXIRI) versus conventional adjuvant therapy (CAPOX). The primary objective in this phase is to study differences on the conversion rate between both groups. An academic assay based on tumor informed approach is used for ctDNA determination. Tumor and germline samples analysis are carried out by an in-house-developed bioinformatics pipeline specialized in variant-calling analysis using a custom 29-gene panel. Somatic variants are identified by the germline mutations extraction. Different annotation databases and an internal pathological mutation database are used to rule out potential benign somatic variants. Those candidate somatic mutations with the highest allelic frequency are selected and a specific panel of amplicons is designed to monitor their presence in ctDNA using NGS. Plasma samples analysis is carried out by an in-house pipeline specialized in reducing potential background noise. To assess panel performance in both sample types, the bioinformatics pipelines include a set of methods to calculate and filter according to different quality control metrics. Recruitment for the Phase IIa is ongoing with a total of 67 pre-screened out of which two patients were eligible. Clinical trial information: 2021-000. 507-20 .

A retrospective study of postoperative targeted therapy in ALK-positive lung cancer

In this study, we aim to investigate the therapeutic effect and safety of ALK inhibitor in ALK-positive lung cancer patients. 59 patients with ALK-positive lung cancer from August 2013 to August 2022 were retrospectively recruited. The basic information, pathological type, clinical stage and treatment strategy were collected. These patients were divided into two groups, including 29 patients of conventional adjuvant chemotherapy, and 30 cases of targeted therapy. The patients in the targeted therapy group underwent adjuvant targeted therapy with crizotinib for 2 years. The observation indicators include curative effects and adverse events. The disease-free survival (DFS) and overall survival (OS) were also analyzed. We analyzed the pathological stages after adjuvant chemotherapy and targeted therapy in lung cancer, no significant difference in the p stage N and T was found between the two therapeutic groups. However, the DFS events, DFS median time and OS median time showed significant improvement in the targeted therapy group when compared with adjuvant chemotherapy (all P < 0.05). Besides, the patients under both therapeutic regimens presented some adverse events, among them elevated aspartate transaminase/alanine aminotransferase was the most common adverse event in all the patients, followed by nausea and vomiting. Our study identified that crizotinib-based postoperative targeted therapy helps improve the prognosis of patients with ALK-positive lung cancer, confirming that postoperative targeted therapy can be considered an effective and feasible therapeutic alternative.

Glucotropaeolin Promotes Apoptosis by Calcium Dysregulation and Attenuates Cell Migration with FOXM1 Suppression in Pancreatic Cancer Cells.

Pancreatic ductal adenocarcinoma (PDAC) has naturally aggressive characteristics including postoperative recurrence, resistance to conventional treatment, and metastasis. Surgical resection with chemotherapeutic agents has been conducted as the major treatment for PDAC. However, surgical treatment is ineffective in the case of advanced cancer, and conventional adjuvant chemotherapy, including gemcitabine and 5-fluorouracil, show low effectiveness due to the high drug resistance of PDAC to this type of treatment. Therefore, the development of innovative therapeutic drugs is crucial to solving the present limitation of conventional drugs. Glucotropaeolin (GT) is a glucosinolate that can be isolated from the Brassicaceae family. GT has exhibited a growth-inhibitory effect against liver and colon cancer cells; however, there is no study regarding the anticancer effect of GT on PDAC. In our study, we determined the antiproliferative effect of GT in PANC-1 and MIA PaCa-2, representative of PDAC. We revealed the intracellular mechanisms underlying the anticancer effect of GT with respect to cell viability, reactive oxygen species (ROS) accumulation, alteration of mitochondrial membrane potential (MMP), calcium dysregulation, cell migration, and the induction of apoptosis. Moreover, GT regulated the signaling pathways related to anticancer in PDAC cells. Finally, the silencing of the forkhead box protein M, a key factor regulating PDAC progression, contributes to the anticancer property of GT in terms of the induction of apoptosis and cell migration. Therefore, GT may be a potential therapeutic drug against PDAC.

Metaplastic Breast Carcinoma (MBC), Primary Squamous Cell Carcinoma Subtype in A 49-Year-Old Woman: A Case Report

Introduction: Metaplastic Breast Carcinoma (MBC) is quite a challenging case because metaplastic breast cancer is one of the rarest subtypes of invasive breast cancer. It is reported that MBC occurs only 0.2 to 1% throughout the world. The metaplastic changes can be squamous cells or other mesenchymal cell types. Clinically, MBC presents as a large palpable mass and may be associated with rapid growth. The size of MBC tends to be larger compared with other types of invasive breast cancer ranging from 1 to more than 10 cm. Although there are several main categories of MBC, some carcinoma can be difficult to classify due to their unusual histologic patterns. This case report study is to provide a clinicopathological overview and approach to MBC.Case Presentation: We reported a 49-year-old woman who suffered from a breast mass that rapidly grew for less than one year. The microscopic findings showed squamous cell carcinoma. While molecular studies revealed triple negative results for hormone receptors although Human Epidermal Growth Factor Receptor 2 (HER2) overexpression was unusual (&lt; 5%). Then, we confirmed with chromogen in situ hybridization (CISH) and there was no gen amplification for HER2. Microscopically, we found ductal carcinoma in situ and this finding supported breast origin.Conclusions: Metaplastic carcinoma did not have any specific and distinctive signs clinically. Metaplastic carcinoma can be monophasic (with only a metaplastic component) or biphasic with two or more components. As treatment options, our patient received conventional chemotherapy. Metaplastic breast cancer is reported to have a lower response rate to conventional adjuvant chemotherapy and worse clinical outcome after chemotherapy than other forms of triple-negative breast cancer.

Primary Urethral Carcinoma in a Bitch - Multimodal Treatment

Background: Urethral tumors are uncommon in canines, represented predominantly by transitional cell carcinoma, marked by aggressive behavior associated with short life expectancy. Definitive diagnosis is achieved by histopathological analysis. Surgery associated with chemotherapy is the main therapeutic alternative. The aim of this paper is to report a case of primary transitional cell carcinoma of the urethra in a bitch, submitted to surgical treatment associated with conventional adjuvant chemotherapy and metronomic chemotherapy, achieving survival of 21 months, to date. Case: A 12-year-old bitch mixed breed was admitted at the Veterinary Hospital of Federal Rural University of Rio de Janeiro (UFRRJ), manifesting hematuria and urinary incontinence for one month. Physical examination indicated that vital parameters were within normal limits. Laboratory tests of blood count and serum biochemistry, urinalysis, culture, urinary antibiogram, and abdominal ultrasound were performed. The ultrasound image suggested a neoplastic urethral process. Because of the suspicion of neoplasm, a thoracic X-ray was performed, showing no evidence of metastasis. Computed tomography (CT) of the abdominal region was performed, revealing an expansive lesion in the urethra with loss of definition of the walls and urethral lumen extending to the level of the pelvic floor, measuring about 2.9 x 1.4 x 1.2 cm. After pre-anesthetic exams, the animal underwent resection and surgical anastomosis of the affected urethral region. The sectioned tissue was sent for histopathological analysis, with diagnosis of transitional cell carcinoma. Adjuvant chemotherapy was performed using carboplatin at a dose of 250 mg/m², intravenously, every 21 days for 6 sessions. After completing the protocol, abdominal ultrasonography was performed again, which showed a cicatricial process in the urethral region of the surgical excision, with no sign of tumor recurrence. A metronomic chemotherapy protocol was then started with cyclophosphamide at a dose of 15 mg/m², daily for 6 months, with periodic oncological follow-up. At the end of the period, the animal remained under periodic follow-up with ultrasound exams performed at 2-month intervals, and has been free from recurrence for 21 months until now. Discussion: Urethral neoplasms account for 0.5 - 2% of all canine tumors, and are represented mostly by transitional cell carcinomas. Clinical signs of urinary obstruction and hematuria are the most common, as reported in the patient in question. The definitive diagnosis is by histopathological examination. However, imaging tests such as computed tomography are important in the initial investigation and surgical planning. The indicated treatment is surgical resection of the mass with subsequent adjuvant chemotherapy or radiotherapy. The chemotherapy protocol associating cisplatin and piroxicam can achieve remission rates of 70%, but this association has a high nephrotoxic effect. In the present case, cisplatin was replaced by carboplatin in order to reduce the nephrotoxic effects of chemotherapy. The metronomic protocol using cyclophosphamide was used as maintenance therapy, at the end of the conventional chemotherapy protocol. Survival achieved was longer than that described in the literature in cases of transitional cell carcinomas in the urethral region. Therefore, multimodal therapy using surgery associated with conventional and metronomic chemotherapy, is an option in canines with urethral carcinoma. Keywords: canine, urethral neoplasm, surgery, chemotherapy. Título: Carcinoma uretral primário em uma cadela - tratamento multimodal Descritores: canino, neoplasia uretral, cirurgia, quimioterapia.

Rare Case of Metaplastic Breast Carcinoma with Squamous Differentiation in Young Female: A Case Report

Background. Metaplastic breast carcinoma is a very rare breast cancer, only about 0.2"‘1% of all invasive breast carcinomas. The prognosis of these cancer is poor and aggressive, reported to have lower response rates to conventional adjuvant chemotherapy and a worse clinical outcome after chemotherapy than other forms triple"‘negative breast carcinomas. Histopathologically, metaplastic breast carcinoma has distinct patterns with different outcomes. Among the types of metaplastic carcinoma, squamous cell, high grade spindle cell and high grade adenosquamous carcinoma are associated with the worst prognosis. We report one case of metaplastic breast carcinoma with squamous differentiation in young patient.&#x0D; Methods. We examined the breast tumor tissue of a female patient, evaluated the macroscopic and microscopic features and asked the patient about the clinical course of the disease. Inform consent was obtained from the patient for publication of this case report and accompanying images.&#x0D; Results. We reported a young female patient with final diagnosis of pathology Mixed Infiltrating Duct Carcinoma of No Special Type Grade 3 and Metaplastic Breast Carcinoma with Squamous Differentiation (30%) that has invaded fat tissue with Ductal Carcinoma Insitu of High Nuclear Grade 3 with basis of the operation is still positive for the tumor mass. Patients lost follow"‘up and did not continue therapy.&#x0D; Conclusion. Morphology of metaplastic breast carcinoma are important factors influencing patient outcome. Early diagnosis and wide local excision of the squamous"‘type metaplastic breast carcinoma mass can make a better prognosis.

Clinical efficacy and safety of early adjuvant chemotherapy for stage III colon cancer: Short-term outcomes of a multicenter, randomized, open-label, phase 3 trial.

3598 Background: Adjuvant chemotherapy (AC) is recommended to commence within 8 weeks since after surgical resection of stage II or III colon cancer. Results of many retrospective studies showed inferior survival outcomes following delay of AC delay. Moreover, preclinical studies showed that the progression of disseminated cancer cells is profound during the postoperative period. This study is the first prospective trial to evaluate early (≤ 14 days postoperative) AC for patients (pts) with stage III colon cancer. Methods: This study is a prospective, multicenter, randomized phase III trial. Pts with pathological stage III colon cancer were enrolled and randomized 1:1 to early AC (starting AC ≤ 14 days after surgery) or conventional AC (starting AC &gt; 14 days after surgery). Pts were recommended to receive 12 cycles of FOLFOX-6 for AC. The primary endpoint was disease-free survival. The secondary endpoints were overall survival, adverse events, surgical complication during AC, and patient-reported outcomes (quality of life) during 1 year after surgery. Herein, safety data, chemotherapy delivery, and quality of life are presented. Results: This study randomized 443 pts either early AC arm (221pts) or early AC arm (222 pts) to the during September 2011 to March 2020. 380 pts who received at least one cycle of FOLFOX-6 were included in the safety analysis (192 and 188 in the early and conventional AC arms, respectively). The baseline characteristics of the two groups were well-balanced except for the interval from the surgery to the initial AC. The early and conventional AC arms started their first chemotherapy at median of 13 (4-43 days) and 29 (17-53 days) after surgery (p &lt; 0.001), respectively. No significant differences were seen in the median chemotherapy cycles, AC completion, and relative oxaliplatin dose intensity between groups. AC Completion without any change of dose or schedule delay was seen in 18% and 20% in early and conventional AC arms respectively, while dose reduction or delay was 65% and 61%, respectively. Toxicities of grade 3 or more were seen in 28% in both groups. One patient in the early AC arm underwent an emergent operation for anastomotic leakage on the second day of 5-fluorouracil infusion (postoperative day 14). However, the surgical complication was not seen in any other patient. The scores of the European Organization for Research and Treatment of Cancer Quality of Life core 30 questionnaire were similar in both arms at baseline (before starting AC), and 1 month, 3 months, 6 months, and 12 months after surgery. Conclusions: Early AC was safe and did not increase either chemotherapy-related adverse events or surgery-related complications during treatment. Moreover early AC did not reduce the quality of life of the pts during 1 year after surgery. This study continues to follow-up the patients for survival outcomes. Clinical trial information: NCT01460589.

Role of prophylactic hyperthermic intraperitoneal chemotherapy in patients with locally advanced gastric cancer.

BACKGROUNDGastric cancer is the second most common malignant tumor in China, ranking third among all malignant tumor mortality rates. Hyperthermic intraperitoneal chemotherapy (HIPEC) has been shown to increase significantly the effectiveness of intraperitoneal chemotherapeutic drugs, prolong the action time of these drugs on intraperitoneal tumor cells, and enhance their diffusion in tumor tissues. HIPEC may be one of the best choices for the eradication of residual cancer cells in the abdominal cavity.AIMThe aim of this study was to study the role of preventive HIPEC after radical gastrectomy.METHODSA prospective analysis was performed with patients with cT4N0-3M0 gastric cancer to compare the effects of postoperative prophylactic HIPEC plus intravenous chemotherapy with those of routine adjuvant chemotherapy. Patients’ medical records were analyzed, and differences in the peritoneal recurrence rate, disease-free survival time, and total survival time between groups were examined.RESULTSThe first site of tumor recurrence was the peritoneum in 11 cases in the conventional adjuvant chemotherapy group and in 2 cases in the HIPEC group (P = 0.020). The 1-year and 3-year disease-free survival rates were 91.9% and 60.4%, respectively, in the conventional adjuvant chemotherapy group and 92.1% and 63.0%, respectively, in the HIPEC group. The 1-year and 3-year overall survival rates were 95.2% and 66.3%, respectively, in the conventional adjuvant chemotherapy group and 96.1% and 68.6%, respectively, in the HIPEC group. No significant difference in postoperative or chemotherapy complications was observed between groups.CONCLUSIONIn patients with cT4N0-3M0 gastric cancer, prophylactic HIPEC after radical tumor surgery is beneficial to reduce peritoneal tumor recurrence and prolong survival.

The history, present situation, and future directions of neoadjuvant chemotherapy for HER2-negative breast cancer.

Chemotherapy has played a significant role in breast cancer therapy and dramatically improved the outcome of breast cancer patients. Neoadjuvant chemotherapy (NAC) is defined as chemotherapy conducted before surgery. The rationale for NAC in operable breast cancer is that the benefit of systemic chemotherapy on the long-term prognosis does not change, regardless of whether chemotherapy is conducted before or after surgery. NAC is now widely used for early and advanced breast cancer patients since it has two significant advantages over conventional adjuvant chemotherapy after surgery. One is that the rate of the breast-conserving surgery increase resulted from tumor shrinkage during NAC, which can contribute to a minimal invasion from surgical therapy and good quality of life following therapy. Another is that a response to chemotherapy can be observed in in-vivo setting. Patients who achieve the pathological complete response (pCR) show a favorable prognosis. Thus, the response to NAC can be used as an indicator for personalized medicine. To date, novel agents for NAC have been explored in randomized trials, setting the pCR rate as an endpoint. Also, response- and residual disease-guided therapy have been ready for prime time in daily practice. The author describes the history, current situation, and future direction of NAC for HER2-negative breast cancer in the review article.

Fast-track multidisciplinary treatment versus conventional treatment for colorectal cancer: a multicenter, open-label randomized controlled study

BackgroundLaparoscopic surgery, fast-track perioperative treatment and XELOX chemotherapy are effective strategies for shortening the duration of hospital stay for cancer patients. This trial aimed to clarify the safety and efficacy of the fast-track multidisciplinary treatment (FTMDT) model compared to conventional surgery combined with chemotherapy in Chinese colorectal cancer patients.MethodsThis trial was a prospective randomized controlled study with a 2 × 2 balanced factorial design and was conducted at six hospitals. Patients in group 1 (FTMDT) received fast-track perioperative treatment and XELOX adjuvant chemotherapy. Patients in group 2 (conventional treatment) received conventional perioperative treatment and mFOLFOX6 adjuvant chemotherapy. Subgroups 1a and 2a had laparoscopic surgery and subgroups 1b and 2b had open surgery. The primary endpoint was total length of hospital stay during treatment.ResultsA total of 374 patients were randomly assigned to the four subgroups, and 342 patients were finally analyzed, including 87 patients in subgroup 1a, 85 in subgroup 1b, 86 in subgroup 2a, and 84 in subgroup 2b. The total hospital stay of group 1 was shorter than that of group 2 [13 days, (IQR, 11–17 days) vs. 23.5 days (IQR, 15–42 days), P = 0.0001]. Compared to group 2, group 1 had lower surgical costs, fewer in-hospital complications and faster recovery (all P < 0.05). Subgroup 1a showed faster surgical recovery than that of subgroup 1b (all P < 0.05). There was no difference in 5-year overall survival between groups 1 and 2 [87.1% (95% CI, 80.7–91.5%) vs. 87.1% (95% CI, 80.8–91.4%), P = 0.7420].ConclusionsThe FTMDT model, which integrates laparoscopic surgery, fast-track treatment, and XELOX chemotherapy, was the superior model for enhancing the recovery of Chinese patients with colorectal cancer.Trial registrationClinicalTrials.gov: NCT01080547, registered on March 4, 2010.

Promises of targeted therapy for low grade gliomas in children

Low grade gliomas are the most common brain tumors in children. Total resection for operable lesion helps to achieve local and system control. Nevertheless, for inaccessible tumors are required more effective treatment both to overcome the refractory course of the disease, and to mi nimize toxicity with conventional adjuvant chemotherapy and various types of radiation therapy. In recent years, there has been an accelerated understanding of the molecular pathogenesis of some tumors in children, including low grade gliomas. Given the fact that the basis of the molecular pathogenesis of the low grade gliomas is the activation of signaling pathways MARK (mitogen activated protein kinase) and mTOR (mammalian target of rapamycin), the most promising targeted agents are BRAF, MEK and mTOR inhibitors. Nevertheless, a number of other agents have been studied to find promising targeted therapy for this tumors type. This article summarizes the latest literature evaluating new drugs in low grade glioma.

Apical Lymph Nodes in the Distant Metastases and Prognosis of Patients with Stage III Colorectal Cancer with Adequate Lymph Node Retrieval Following FOLFOX Adjuvant Chemotherapy.

The aim of the study was to assess apical lymph nodes (APNs) for predicting distant metastases in patients with stage III colorectal cancer (CRC) curatively treated with FOLFOX adjuvant chemotherapy and adequate lymph node retrieval. We investigated the correlation between APN metastasis and clinical outcomes. This retrospective study examined 97 patients. All patients were followed until death, loss to follow-up, or May 2017. Clinicopathological variables, including the APN status, were assessed. Multivariate logistic regression model was used to identify the independent risk factors for APN and distant metastases, and Cox proportional regression model was used to evaluate the association between APN metastasis and oncologic outcomes. Multivariate analyses revealed the N2 stage as an independent predictor of APN metastasis [P = 0.036; odds ratio (OR): 3.016; 95% confidence interval (CI): 1.076-8.499], while APN metastasis was an independent risk factor for distant metastases (P < 0.001; OR: 13.876; 95% CI: 3.815-50.475). Furthermore, APN metastasis was an independent risk factor for poorer disease-free survival (DFS) and overall survival (OS) (P < 0.001 and P = 0.005, respectively). The liver (31.6%) was the most common site of distant metastases in patients with APN metastases. APN metastasis is an important prognostic factor for node-positive CRC; it enhanced the distant metastases in patients with stage III CRC curatively treated with adequate lymph node retrieval following FOLFOX adjuvant chemotherapy. Therefore, for patients with stage III CRC involving APN metastasis, prospectively randomized trials are mandatory to investigate different therapeutic strategies in addition to conventional FOLFOX adjuvant chemotherapy.

Prognostic Evaluation of Epidermal Growth Factor Receptor (EGFR) Genotype and Phenotype Parameters in Triple-negative Breast Cancers.

Epidermal growth factor receptor (EGFR) aberrations have been implicated in the pathogenesis of triple-negative breast cancer (TNBC) but their impact on prognosis and, therefore, druggability, remain controversial. Herein, we studied EGFR aberrations at different molecular levels and assessed their prognostic impact in patients with operable TNBC treated with adjuvant anthracycline-based chemotherapy. We evaluated the prognostic impact of EGFR gene status by fluorescent in situ hybridization (FISH), EGFR coding mutations by Sanger and next-generation sequencing, relative EGFR messenger RNA (mRNA) levels by qPCR (upper quartile) and EGFR and p53 protein expression by immunohistochemistry (IHC), in 352 centrally-assessed tumors from an equal number of TNBC patients. Approximately 53.5% of the tumors expressed EGFR, 59.3% p53 and 35.9% both EGFR and p53 proteins; 4.1% showed EGFR gene amplification and 4.4% carried EGFR mutations. The latter were located outside the druggable kinase domain region and presented at low frequencies. Amplification and mutations overlapped only in one case of glycogen-rich carcinoma. EGFR and CEN7 copies were higher in tumors from older patients (p=0.002 and p=0.003, respectively). Patients with amplified tumors (n=11) had excellent prognosis (0 relapses and deaths). Upon multivariate analysis, high EGFR copies conferred significantly favorable disease-free survival (HR=0.57, 95% CI 0.36-0.90, Wald's p=0.017) and high CEN7 copies favorable overall survival (HR=0.49, 95% CI=0.29-0.83, Wald's p=0.008). Patients with EGFR-/p53+ and EGFR+/p53- tumors had significantly higher risk for relapse than those with EGFR-/p53- and EGFR+/p53+ tumors (HR=1.73, 95% CI=1.12-2.67, Wald's p=0.013). EGFR gene amplification and mutations are rare in TNBC, the latter of no apparent clinical relevance. Surrogate markers of EGFR-related chromosomal aberrations and combined EGFR/p53 IHC phenotypes appear to be associated with favorable prognosis in patients with operable TNBC receiving conventional adjuvant chemotherapy.

A Retrospective Study of Stage I to IIIa Lung Adenocarcinoma After Resection: What Is the Optimal Adjuvant Modality for Patients With an EGFR Mutation?

BackgroundAdjuvant cisplatin-based chemotherapy improves non–small-cell lung cancer (NSCLC) 5-year survival rates after resection. However, adjuvant epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) efficacy and the optimal adjuvant treatment are unclear. Patients and MethodsThe clinical records of patients tested for EGFR mutation after complete NSCLC resection were reviewed and tested for significance; EGFR mutation and adjuvant therapy effects on survival were assessed using univariate and Cox regression analyses. ResultsWe enrolled 257 patients (stage I, 126; stage II-IIIa, 131); 138 had EGFR mutation. EGFR mutation status was unrelated to recurrence (hazard ratio [HR], 0.83; 95% confidence interval [CI], 0.572-1.204; P = .326) or death (HR, 0.679; 95% CI, 0.406-1.136; P = .14). Thirty-one patients with EGFR mutation received adjuvant EGFR-TKIs; most (87.1%) received EGFR-TKI monotherapy. Patients who received adjuvant EGFR-TKIs had longer disease-free survival (DFS) than those who did not (P = .033) or received conventional adjuvant chemotherapy (P = .038). Adjuvant EGFR-TKIs did not affect overall survival (OS; P = .258), although the recipients had better 3-year OS (92.5% vs. 81%). Eight patients who received adjuvant EGFR-TKI developed disease recurrence, which occurred in 7 patients during adjuvant treatment. In the adjuvant EGFR-TKI group patients with a primary tumor EGFR mutation, EGFR mutation in the corresponding metastatic lymph nodes did not affect DFS, but patients who received EGFR-TKI after recurrence had longer progression-free survival (P = .087). ConclusionIn patients with an EGFR mutation, adjuvant EGFR-TKI monotherapy after complete resection significantly prolongs DFS compared with adjuvant chemotherapy and/or radiotherapy.

Targeted Therapy in Pediatric Low-Grade Glioma

Collectively, pediatric low-grade gliomas account for most brain tumors reported in children. Surgery is typically curable for operable lesions. However, more effective therapies are required for inaccessible tumors, both to overcome refractory disease and to minimize the toxicity associated with conventional adjuvant chemotherapy and radiotherapy regimens. Recent years have witnessed rapid improvements in our understanding of the molecular pathogenesis of several childhood tumors, including low-grade gliomas. As a result, several novel compounds targeting and inhibiting critical components of molecular signaling pathways purported to be overactive in the disease have been developed. This article summarizes the most recent literature evaluating such novel targeted agents in childhood low-grade gliomas.

Five year retrospective survival analysis of triple negative breast cancer in North-West India

In our institute, about 10% of total cancer is female breast cancer. This analysis was performed to check triple negativity among these patients with their survival strength up to 5 years in relation to different age groups, stage and chemotherapy protocols. 208 immunohistochemistry proved triple negative breast cancer patients registered and treated until 2008 were retrospectively selected for the study. Overall survival up to 5 years was observed on the basis of stage, different age groups and chemotherapy regimens. All patients had undergone surgery, conventional external beam radiation therapy and adjuvant chemotherapy. The survival analyses were performed using the Kaplan-Meier method. The majority of patients (41%) were in the age group 21-30 years. Stage IV was seen in 18% of the patients at diagnosis and mainly in 21-40 years age group. Only 3% of females were >70 years age and were of Stage I and II. Overall 5 year survival in Stage I in Cyclophosphamide, Adriamycin/Epirubicin, 5-Flurouracil group was 37.5% as compared with Docetaxel/Paclitaxel, Epirubicin group 93% (P < 0.0001). Triple negativity in North-West India is about 11.8%. We observed it in younger patients mainly with highly aggressive behaviors. Taxane based chemotherapy gives better result as compared with anthracycline based regimens in all stages.