Adjuvant Chemotherapy Protocols Research Articles

Changes in Epicardial Adipose Tissue Assessed by Chest CT in Breast Cancer Patients Receiving Adjuvant Chemotherapy with Anthracyclines and Trastuzumab.

Cardiotoxicity (CTX) induced by adjuvant chemotherapy is a significant factor that impacts the prognosis and quality of life in breast cancer (BC) patients. In this study, we aimed to investigate the changes in epicardial adipose tissue (EAT) before and after treatment in BC patients who received anthracyclines adjuvant chemotherapy protocol (AC-T) and anthracyclines combined with trastuzumabadjuvant chemotherapy protocol (AC-TH). Additionally, we assessed whether there were any differences in the changes in EAT between the two groups of patients. Our objective was to examine the effects of anthracyclines and trastuzumab on EAT and determine the potential role of EAT changes on CTX. We reviewed female BC patients who were treated with adjuvant chemotherapy protocols of AC-T and AC-TH, all of whom underwent baseline (T0) and follow-up (T1) chest computed tomography (CT) and echocardiography. A cohort of healthy women, matched in age, underwent two chest CTs. EAT was quantified on chest CT using semi-automated software. CTX was defined as a 10% reduction in left ventricular ejection fraction (LVEF) from baseline, with an absolute value of 53%. A total of 41 BC patients were included in the study, with 23 patients in the AC-T group and 18 patients in the AC-TH group. Additionally, 22 healthy females were included as the normal group. None of the BC patients developed CTX after chemotherapy. The age did not differ significantly between the normal group and the AC-T group (p = 0.341) or the AC-TH group (p = 0.853). Similarly, the body mass index (BMI) of the normal group was comparable to that of the AC-T group (p = 0.377, 0.346) and the AC-TH group (p = 0.148, 0.119) before and after chemotherapy. The EAT volume index (mL/kg/ ) was significantly higher in both the AC-T group (5.11 1.85 vs. 4.34 1.55, p 0.001) and the AC-TH group (4.53 1.61 vs. 3.48 1.62, p 0.001) at T1 compared with T0. In addition, both the AC-T group (-72.95 5.01 vs. -71.22 3.91, p = 0.005) and the AC-TH group (-72.55 5.27 vs. -68.20 5.98, p 0.001) exhibited a significant decrease in EAT radiodensity (HU) at T1 compared to T0. However, there was no significant difference observed in the normal group. At T0, no difference was seen in EAT volume index (4.34 1.55 vs. 3.48 1.62, p = 0.090) and radiodensity (-71.22 3.91 vs. -68.20 5.98, p = 0.059) between the AC-T and AC-TH groups. Similarly, at T1, there was still no significant difference observed in the EAT volume index (-5.11 1.85 vs. 4.53 1.61, p = 0.308) and radiodensity (-72.95 5.00 vs. -72.54 5.27, p = 0.802) between the two groups. BC patients who underwent AC-T and AC-TH adjuvant chemotherapy protocols demonstrated a significant rise in the volume index of EAT, along with a substantial reduction in its radiodensity post-chemotherapy. These findings indicate that alterations in EAT could potentially aid in identifying cardiac complications caused by chemotherapeutic agents and remind clinicians to focus on changes in EAT after adjuvant chemotherapy in BC patients to prevent the practical occurrence of CTX.

Prognostic value of the CRM status in pancreatic ductal adenocarcinoma: Data from a regional cancer registry.

632 Background: Ductal pancreatic adenocarcinoma (PDAC) still has a dismal prognosis even when deemed resectable. A cancer free resection margin (R0) is associated with a more favourable prognosis than the presence of tumour cells at resection margin (R1). However, the precise definition of the R0 status is still a matter of debate in PDAC. For a more accurate determination of R0 in PDAC the concept of circumferential resection margins (CRM) has been introduced. However, an international standardized nomenclature of CRM is still missing, and the clinical value of the CRM concept is not yet fully established. Here we evaluate whether the CRM status as defined in the national German S3 guideline is an independent prognostic factor in PDAC using data from the regional cancer registry of the State of Baden Württemberg in Germany. Methods: Data from the cancer registry of the State of Baden-Württemberg, Germany were collected, using documented patients diagnosed with invasive ductal adenocarcinoma of the pancreas between 2015 and 2020. The R-status was assessed according to the national German S3 guideline with R0 wide/CRM- when CRM is > 1mm, R0 narrow/CRM+ when CRM is £ 1 mm from the tumour and R1 when tumour cells are found at the resection margin. Progression free survival (PFS) as well as 3-year overall survival (OS) were assessed using Kaplan-Meier statistics and multivariable Cox regression models (adjusted for age, pN stage, primary tumor location and systemic treatment). Results: In total we identified 1098 cases surgically treated for pancreatic cancer and fulfilling the inclusion criteria. 340 patients had an R0 wide/CRM- resection, 410 patients an R0 narrow/CRM+ resection, and 348 patients an R1 resection. The R0 wide/CRM- status was associated with a significantly increased median 3-year OS rate compared to the other two groups (51,5%, 37,4% and 26,7% for R0 wide/CRM-, R0 narrow/CRM+ and R1, respectively). mPFS was also longer in the R0 wide/CRM- group. These findings were robust with regards to grading. 5-FU based adjuvant treatment was mainly mFOLFIRINOX and show better outcome as compared to gemcitabine-based treatments. Conclusions: The present study was performed using real world data reflecting actual clinical settings. The results obtained are in good agreement with data from clinical trials, including the prognostic role of the R- and N- Status as well as the efficacy of adjuvant chemotherapy protocols used.

Ultrassonografia modo-B e Doppler dos rins de cadelas com neoplasias mamárias submetidas à quimioterapia adjuvante

ABSTRACT: Mammary neoplasia represents the most frequently diagnosed type of neoplasia in bitches. Although surgical removal is the procedure of choice for therapeutic management, chemotherapy protocols appear as important allies and adjuvants. Despite the great advances that have occurred in the field of cancer therapy, the systemic repercussions of these drugs still impose important limitations on their use. In this sense, the development of increasingly targeted therapeutic protocols and preventive monitoring of patients represent important strategies to avoid possible complications - among them, Acute Kidney Injury (AKI). Routinely, ultrasound evaluation is used to identify morphological or metastatic variations in abdominal cavity organs. Acting complementary to the B-mode evaluation, Doppler mapping proves to be efficient in recognizing alterations in vascular hemodynamics. Therefore, the objective of the present study was to evaluate the use of B-mode and Doppler ultrasound to identify renal morphological and hemodynamic alterations in bitches with mammary neoplasia submitted to adjuvant chemotherapy protocols that associate gemcitabine with carboplatin. Thirteen bitches were included, without distinction of breed and between seven and 13 years of age. The animals were evaluated ultrasonographically at two different times during three consecutive chemotherapy cycles: before (T0) and one and a half hours after each cycle (T1), for 42 days. No morphological changes were observed in B-mode throughout the chemotherapy protocol. However, the Doppler velocimetry indices demonstrated statistical differences before (T0) and after (T1) the administration of the drugs. It was concluded that Doppler ultrasound could be used as a complementary method for monitoring the renal response of patients exposed to nephrotoxic drugs and potentially causing renal injury.

Resection of Gastric Cancer Liver Metastases: Literature Review and Case Report

Introduction: The treatment of gastric cancer has undergone changes in recent years, significantly impacting the morbidity and mortality caused by the disease. However, the treatment of metastatic disease remains a challenge. Whether in the intestinal or Lauren's diffuse tumor, the presence of liver metastases in gastric cancer is considered to be an unfavorable prognosis, given the possibility of the existence of other occult metastases at the time of this diagnosis. Given the changes in the panorama of this disease, it is necessary to review the proposed treatment, considering the possibility of oncological benefit from liver metastasectomy and which patients would benefit from this therapy. Clinical case: FAM, female, 65 years old, diagnosed with Lauren's intestinal-type gastric adenocarcinoma submitted to subtotal gastrectomy with D2 lymphadenectomy. Clinical staging IIIB (T4N2M0), referred for adjuvant chemotherapy protocol. At the time no synchronous distant metastases was identified. One year later PET-CT showed a liver nodule at the right lobe and peri-portal nodule. Submitted to right hepatectomy + peri-portal lymphadenectomy. Anatomopathological exame confirmed gastric adenocarcinoma. Conclusion: Review of published studies in the literature showed that patients who would benefit from this therapy would be those with 1-3 metastatic liver lesions, up to 5 cm in length in the largest one, without serosa invasion in the primary lesion and whose lymph node involvement was ≤ N1 . Overall patient survival was increased from 9.5-14.1 months to 31.1-40.8 months in these groups. We therefore conclude that there is benefit in resection of liver metastases in selected cases of gastric cancer.

Health-related quality of life of glioblastoma patients receiving post-operative concomitant chemoradiotherapy plus adjuvant chemotherapy: A longitudinal study

BackgroundGlioblastoma (GBM) is an aggressive primary malignant brain tumour with a dismal prognosis, despite the improvement from the new establishment of post-operative treatment protocol of concomitant chemoradiotherapy (CCRT) plus adjuvant chemotherapy. This study aimed to evaluate the health-related quality of life (HRQoL) in post-operative GBM patients treated with CCRT plus adjuvant chemotherapy with subjective standardised questionnaires at various time points. MethodsPatients with newly diagnosed GBM who were treated at our centre with post-operative CCRT plus adjuvant chemotherapy were included. Their HRQoL scales were measured with the European Organisation for Research and Treatment of Cancer (EORTC) CLC30 and BN20 questionnaires. Assessments were made before the beginning of post-operative CCRT, and at 0 (within 2 weeks), 3 and 6 months after the end of CCRT. A mixed-level linear model was used to analyse the change in each HRQoL scale over time. Results21 patients were recruited with a median overall survival of 27 months (range:4–55 months). There was no significant change in the global health status over time. An improvement in insomnia and an aggravation in communication deficit were found with statistical significance and clinical meaningfulness. Greater improvement in insomnia was associated with methylated MGMT gene promoter in the tumour while worse aggravation in communication deficit was associated with older age (≥65). ConclusionsThe global health status did not worsen during post-operative CCRT plus adjuvant chemotherapy, while the severity of insomnia lessened and communication deficit worsened. This may provide insight for clinicians to formulate treatment plan for patients with GBM.

Clinical and Laboratory Findings in Dogs Undergoing Adjuvant Chemotherapy with Gemcitabine/Carboplatin Combination for Mammary Neoplasia

Adjuvant chemotherapy might be indicated in some canine mammary cancer cases due to metastatic potential. In this regard, studies to determine adverse events following chemotherapy protocols are valuable. The purpose of this prospective clinical trial was to evaluate the safety and tolerability of gemcitabine and carboplatin combination in dogs with malignant mammary tumors. For this prospective clinical trial, 21 female dogs mastectomized due to malignant mammary neoplasia underwent adjuvant chemotherapy with gemcitabine (3 mg/kg, 60-minute IV infusion) and carboplatin (10 mg/kg, 20-minute IV infusion) based protocol every 21 days for three cycles. They were monitored periodically for treatment-related adverse events by clinical and laboratory evaluations. A total of 17 (80.9%) dogs developed leukopenia, 10 (47.6%) neutropenia, and 15 (71.4%) thrombocytopenia at least once along with the three chemotherapy cycles. All these hematologic toxicities were grade 1, 2, or 3. Two (9.5%) animals had evidence of gastrointestinal toxicity; however, clinical signs were mild to moderate (grades 1 and 2). No dog had life-threatening adverse events (grade 4) or even died (grade 5) of treatment-related complications. The adjuvant chemotherapy protocol with gemcitabine and carboplatin was well-tolerated and safe in female dogs for mammary cancer treatment with self-limiting hematological and gastrointestinal adverse events.

COVID‑19 in a patient receiving adjuvant breast cancer chemotherapy with granulocyte olony‑stimulating factor (G‑CSF) support: A case report

Patients receiving chemotherapy are at high risk for severe infections and complications such as acute respiratory syndrome. The most commonly used adjuvant chemotherapy protocols (docetaxel-cyclophosphamide every 3 weeks or the dose-dense regimen, doxorubicin-cyclophosphamide every 2 weeks followed by paclitaxel) incorporate granulocyte-colony stimulating factor (G-CSF). G-CSF is routinely administered to prevent chemotherapy-associated neutropenia but often results in significant neutrophilia. The present case describes a patient with breast cancer who was successfully treated for severe COVID-19 respiratory syndrome while under adjuvant chemotherapy (docetaxel-cyclophosphamide) treatment and long-term G-CSF support. In addition, the potential effect of G-CSF on the respiratory deterioration of the patient given its cardinal role in innate inflammation and, accordingly, the cytokine storm associated with COVID-19 was described. The case described in the present study indicated how solutions to the immunity challenges faced when treating a patient with chemotherapy may be the source of a larger problem within the coronavirus COVID-19 pandemic.

Formulation, Optimization and Evaluation of Nanofiber Based Fast Dissolving Drug Delivery System of Colchicine for Pediatrics

Systemic toxicity is an obstacle against the oral administration of colchicine. The high body surface area to mass ratio in pediatrics would dramatically enhance the toxicity risk. This issue could be jettisoned by formulation of an optimized nanofiber-based fast dissolving delivery system. It could enhance the drug's bioavailability, reduce the administered dose, and bring more convenience and compliance for pediatrics with the problem of consuming conventional dosage forms. The optimized colchicine loaded nanofibers of polyvinyl alcohol 10%w/v with 220.47±16.87 nm mean diameter size exhibits smooth surface and continuous structure in SEM micrographs. No incompatibility was seen in FT-IR analyses. The thermal study illustrated stability enhancement by colchicine loading. The water angle analysis demonstrated its superhydrophilicity and the in vitro release profile illustrated a quick release of colchicine in 30 seconds. As a conclusion, nanofiber-based fast dissolving formulation of colchicine could be suggested as a localized and systemic transmucosal delivery system, immediate-release oral dosage form, and even topical colchicine delivery system that may reduce the risk of systemic toxicity in pediatrics. The antitumor property of CL may also suggest it in rapid neoadjuvant or adjuvant localized chemotherapy protocols for the management of topical tumors in pediatrics.

Current status of perioperative chemotherapy for locally advanced gastric cancer and JCOG perspectives.

Perioperative treatment for locally advanced gastric cancer has been inconsistent between Japan and the Western countries. In Japan, D2 gastrectomy followed by adjuvant chemotherapy is regarded as standard treatment, while neoadjuvant or perioperative chemotherapy is considered to be a standard in the Western countries. Stomach Cancer Study Group of Japan Clinical Oncology Group (JCOG) has conducted many perioperative chemotherapy trials. After the publishing of positive results of ACTS-GC trial, stage-specific adjuvant chemotherapy protocols are planned. JCOG1104 was conducted as to demonstrate the non-inferiority of four courses of S-1 to standard eight courses of S-1, because the efficacy of S-1 appears to be sufficient in stage II. The trial failed to demonstrate the non-inferiority of four courses of S-1. S-1 for 1 year is still recognized to be a standard for stage II gastric cancer. For stage III, studies with more intensive treatments were planned as the efficacy of S-1 monotherapy seems to be insufficient. As in the Western countries, JCOG planned the perioperative chemotherapy. However, the clinical staging is a serious issue to select optimal patients for perioperative chemotherapy. JCOG conducted a prospective cohort study to evaluate the validity of clinical staging in JCOG1302A. From the results of this study, cT3-4 and cN1-3 are selected as optimal candidate for perioperative chemotherapy. JCOG1509 was conducted to demonstrate the superiority of perioperative chemotherapy to adjuvant chemotherapy in these cohorts. Perioperative chemotherapy for marginally resectable tumours such as linitis plastica or extensive nodal disease and special type of cancer like HER2 positive are also conducted.

Clinical impact of adjuvant chemotherapy and radiation for carcinoma stomach: Experience from a tertiary care center.

The main objectives of this study are (1) To assess the patient compliance for adjuvant radiotherapy and chemotherapy for carcinoma stomach, (2) Tolerance of adjuvant radiotherapy with the use of conformal techniques, and (3) Disease-free and overall survival benefits of adjuvant chemotherapy and radiation in carcinoma stomach. Carcinoma stomach patients who registered in the institution during the period of December 2011-2014 were taken for the analysis. Treatment details of patients who received the planned adjuvant treatments, radiotherapy, and chemotherapy were collected. The treatment protocol was made as per the institutional multidisciplinary meeting decisions. The radiotherapy dose given was 45 Gy in 25 fractions using an intensity-modulated radiotherapy technique and concurrent chemotherapy offered with capecitabine 825 mg/m2 twice daily. Adjuvant chemotherapy protocol was selected from the major clinical trial information. A total of 61 patients who satisfied the inclusion criteria were selected. Males 52 (85%) and females (15%). The median age of the patients was 57 years. Stage II patients were 52%, and 48% were stage III. All patients tolerated the planned dose of radiotherapy 45 Gy in 25 fractions, and 74% of patients tolerated six or more cycles of adjuvant chemotherapy. Mean follow-up period was 48 months, and the Kaplan-Meier survival analysis shows 3 and 5 years survival percentages were 57% and 48%, respectively. Adjuvant chemotherapy and radiation using conformal technique are well-tolerated. These were reflected in the overall outcome and survival of the patients. Based on the surgical pathology findings, an individualized approach of adjuvant treatment protocol can improve the outcome.

A network meta-analysis protocol of adjuvant chemotherapy for unresectable patients with advanced gastric cancer.

Background:The treatment methods about surgery, chemotherapy, and radiation therapy were recommended for gastric cancer (GC) patients by National Comprehensive Cancer Network (NCCN) guidelines. However, for the advanced gastric cancer patients or with metastatic lesions who have lost their chance of surgery, the current adjuvant chemotherapy treatments are still controversial. Therefore, this network meta-analysis is mainly to assess the relative efficacy of different adjuvant chemotherapy regimens for advanced gastric cancer (AGC).Methods:In order to compare the relative efficacy among different adjuvant chemotherapy regimens for AGC patients, randomized controlled trials (RCTs) and non-RCTs were systematic searched in PubMed, Web of Science, Clinical Trials, Cochrane Library and Embase database. R-3.4.1 software will be used for data analysis. The risk of bias in RCTs and non-RCTs will be evaluated through the risk of bias tool from the Cochrane Handbook version 5.1.0 and non-randomized studies of interventions (ROBINS-I), respectively.Results and conclusion:The results of this network meta-analysis will evaluate the relative effectiveness and rank the interventions among all chemotherapy methods for unresectable AGC patients, and provide more evidence-based guidance in clinical practice.Protocol registration number:CRD42018111835.

The frequency and predictors of persistent amenorrhea in premenopausal women with colorectal cancer who received adjuvant chemotherapy.

The purpose of this study was to identify the frequency of chemotherapy-induced amenorrhea and associated factors thereof in premenopausal female patients diagnosed with colon cancer. Premenopausal female patients under the age of 50 years who were diagnosed with stages I, II, and III colon cancer were included. A questionnaire surveying personal history including menarche, comorbidities, drugs, other clinical features, and menstrual history during and after completion of chemotherapy was filled by the patients during outpatient visits. Patients who received pelvic radiotherapy were excluded from the study. A total of 60 patients were included in the study. Eleven patients had been treated with surgery alone, and 49 patients had received adjuvant chemotherapy with either fluorouracil (5-FU) alone (n=22) or 5-FU+oxaliplatin (n=27). The frequency of persistent amenorrhea 1 year after receiving chemotherapy was 20% in the whole group, 18% in patients who had received adjuvant chemotherapy with 5-FU alone, and 22% in patients who had received chemotherapy with 5-FU+oxaliplatin. Frequency of persistent amenorrhea was 3.5% in patients under the age of 44 years and 42.8% in patients aged 44 years and older. Multivariate analysis showed that age of 44 years and older (hazard ratio: 29.3; 95% confidence interval: 2.8-309.2, P=0.005) and menarche age of 14 years and older (hazard ratio: 7.6; 95% confidence interval: 1.2-49, P=0.076) were significantly associated with increased risk of persistent amenorrhea. In this study, we found that the frequency of persistent amenorrhea was 20% in patients who received 5-FU monotherapy or oxaliplatin-based adjuvant chemotherapy protocols in colon cancer treatment. Older age and later menarche were the factors that increased the risk of persistent amenorrhea 1 year after chemotherapy.

Squamous cell carcinoma of the breast: A retrospective study.

Squamous cell carcinoma (SCC) of the breast is an extremely rare tumor with vague natural behavior and treatment. The purpose of this study was to identify the clinicopathological features and treatment results of this rare type of breast cancer. The medical files of patients with SCC of the breast presented to Alexandria Main University Hospital during the period from January 1990 to January 2010 were retrospectively reviewed, regarding clinicopathological characteristics and treatment outcome and analyzed. A total of 17 patients were included in this analysis. The median age was 50 years. All patients presented with breast mass. The majority of tumors (88.2%) was negative for hormone receptors. Two-thirds of patients had early T-stage. All patients underwent surgery in our center. Adjuvant tamoxifen was given for two patients. Twelve patients (70.6%) received different adjuvant chemotherapy protocols, and eight patients received radiotherapy. The median disease-free survival was 24 months, and the median overall survival was 40 months. Patients received adjuvant chemotherapy had a statistically significant better disease-free survival (P = 0.014) and overall survival (P = 0.019) compared to patients treated without chemotherapy. Radiotherapy had no significant impact on either disease-free survival or overall survival. SCC of the breast is a very aggressive tumor, and adjuvant chemotherapy should be strongly considered.

Abstract PD7-07: Failure of goserelin to prevent chemotherapy-induced damage to ovarian reserve

Abstract Objective The effectiveness of GnRH analogs (GnRHa) in preserving ovarian reserve and fertility against chemotherapy-induced damage is still being debated. Prior studies generally used menstruation as an outcome measure, which is an unreliable surrogate for fertility. Cyclophosphamide is one of the key components of most commonly utilized adjuvant and neo-adjuvant chemotherapy protocols in breast cancer. Ovarian reserve is made up of quiescent primordial follicles, which are irreversibly damaged by gonadotoxic chemotherapy agents such as cyclophosphamide (Cy) via the induction of double strand DNA breaks (DSBs) that trigger apoptotic oocyte death (Soleimani et al, Aging 2011). There is currently no data on whether GnRHa co-treatment would block chemo-induced primordial follicle DNA damage. We conducted this animal study to determine whether co-administration of a GnRHa would protect cyclophosphamide-induced primordial follicle death and DNA damage. If ovarian suppression by GnRHa does not protect chemotherapy-induced damage to ovarian reserve, then there would be no biological basis for utilizing this strategy for fertility preservation. Design Experimental animal study. Materials and Methods After unilateral oophorectomy, 4-week-old FVB mice received daily 200 mg/kg Cy injections either alone for 3 days (n=4) or with 250 μg/kg Goserelin co-treatment (n=4) starting 3 days before and continuing the duration of chemotherapy. The remaining ovary was recovered at the end of chemotherapy for analysis. Ovaries were fixed and serially sectioned at 5 μm, and every 10th section was analyzed. Primordial (pdf) density, oocyte DSBs (by γH2AX) and apoptotic cell death pathway activation (AC3) were determined by immunostaining and compared between the pre- and post-chemo ovaries of each mice in a paired analysis, as well as between the 2 groups post-chemo. Results Results are summarized in table-1. In both the Cy-only and Cy+GnRHa groups, pdf densities declined significantly compared to pre-chemo (p= 0.003). However, there was no difference between the post-chemo pdf densities of the two groups. Likewise, both Cy and Cy+GnRHa resulted in significantly increased oocyte DNA damage and apoptotic death (p<0.01) compared to baseline readings. However, post-chemo incidence of oocyte DNA damage and apoptotic death were similar between the Cy and Cy+GnRHa groups (p= 0.69 and 0.78, respectively). Impact of GnRHa on Chemo-Induced Ovarian Damage Pre-chemoCyCy+GnRHaCy vs. Pre-chemoCy+GnRHa vs. Pre-chemoCy vs. Cy+GnRHaPdf Density (/mm3)1,300±25.8685±128.4640±121.3<0.01<0.010.8γ-H2AX+ Pdf (%)12.3±0.0871.2±6.975±5.8<0.01<0.010.69AC3+ Pdf (%)053.6±0.638.1±0.06<0.01<0.010.78Pdf: primordial follicle. Data are presented as mean ±SE. P <0.05considered as statistically significant. Conclusions This animal study provides the first direct histologic and molecular evidence that GnRHa co-treatment does not prevent chemotherapy-induced damage to ovarian reserve including potentially mutagenic DNA DSBs in oocytes. Taken together with the recent clinical data utilizing more reliable ovarian reserve markers such as the anti-mullerian hormone (Demeestere et al, J Clin Oncol, 2016), ovarian suppression via GnRHa should not be recommended for the protection of ovarian reserve.(Supported by NIH RO1 HD053112). Citation Format: Oktay K, Taylan E, Sugishita Y, Kawahara T, Suzuki N. Failure of goserelin to prevent chemotherapy-induced damage to ovarian reserve [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr PD7-07.

Effectiveness of multi-drug regimen chemotherapy treatment in osteosarcoma patients: a network meta-analysis of randomized controlled trials

BackgroundOsteosarcoma is the most common malignant bone tumour. Due to the high metastasis rate and drug resistance of this disease, multi-drug regimens are necessary to control tumour cells at various stages of the cell cycle, eliminate local or distant micrometastases, and reduce the emergence of drug-resistant cells. Many adjuvant chemotherapy protocols have shown different efficacies and controversial results. Therefore, we classified the types of drugs used for adjuvant chemotherapy and evaluated the differences between single- and multi-drug chemotherapy regimens using network meta-analysis. MethodsWe searched electronic databases, including PubMed (MEDLINE), EmBase, and the Cochrane Library, through November 2016 using the keywords “osteosarcoma”, “osteogenic sarcoma”, “chemotherapy”, and “random*” without language restrictions. The major outcome in the present analysis was progression-free survival (PFS), and the secondary outcome was overall survival (OS). We used a random effect network meta-analysis for mixed multiple treatment comparisons.ResultsWe included 23 articles assessing a total of 5742 patients in the present systematic review. The analysis of PFS indicated that the T12 protocol (including adriamycin, bleomycin, cyclophosphamide, dactinomycin, methotrexate, cisplatin) plays a more critical role in osteosarcoma treatment (surface under the cumulative ranking (SUCRA) probability 76.9%), with a better effect on prolonging the PFS of patients when combined with ifosfamide (94.1%) or vincristine (81.9%). For the analysis of OS, we separated the regimens to two groups, reflecting the disconnection. The T12 protocol plus vincristine (94.7%) or the removal of cisplatinum (89.4%) is most likely the best regimen.ConclusionsWe concluded that multi-drug regimens have a better effect on prolonging the PFS and OS of osteosarcoma patients, and the T12 protocol has a better effect on prolonging the PFS of osteosarcoma patients, particularly in combination with ifosfamide or vincristine. The OS analysis showed that the T12 protocol plus vincristine or the T12 protocol with the removal of cisplatinum might be a better regimen for improving the OS of patients. However, well-designed randomized controlled trials of chemotherapeutic protocols are still necessary.

Protocol of the PANCALYZE trial: a multicenter, prospective study investigating the tumor biomarkers CXCR4, SMAD4, SOX9 and IFIT3 in patients with resected pancreatic adenocarcinoma to predict the pattern of recurrence of the disease

BackgroundPancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies today with an urgent need for novel therapeutic strategies. Biomarker analysis helps to better understand tumor biology and might emerge as a tool to develop personalized therapies. The aim of the study is to investigate four promising biomarkers to predict the clinical course and particularly the pattern of tumor recurrence after surgical resection.DesignPatients undergoing surgery for PDAC can be enrolled into the PANCALYZE trial. Biomarker expression of CXCR4, SMAD4, SOX9 and IFIT3 will be prospectively assessed by immunohistochemistry and verified by rt.-PCR from tumor and adjacent healthy pancreatic tissue of surgical specimen. Immunohistochemistry expression pattern of all four biomarkers will be combined into a single score. Beginning with the hospital stay clinical data from enrolled patients will be collected and followed. Different adjuvant chemotherapy protocols will be used to create subgroups. The combined biomarker expression score will be correlated with the further clinical course of the patients to test the hypothesis if CXCR4 positive, SMAD4 negative, SOX9 positive, IFIT3 positive tumors will predominantly develop metastatic spread.DiscussionPancreatic cancer is associated with different patterns of progression requiring personalized therapeutic strategies. Biomarker expression analysis might be a tool to predict the pattern of tumor recurrence and discriminate patients that develop systemic metastatic disease from those with tumors that rather develop local recurrence over time. This data might lead to personalized adjuvant treatment decisions as patients with tumors that stay localized might benefit from adjuvant local therapies like radiochemotherapy as compared to those with systemic recurrence who would benefit exclusively from chemotherapy.Moreover, the pattern of propagation might be a predefined characteristic of pancreatic cancer determined by the genetic signature of the tumor. In the future, biomarker expression analysis could be performed on tumor biopsies to develop personalized therapeutic pathways right after diagnosis of cancer.Trial registrationGerman Clinical Trials Register, DRKS00006179.

Minimally invasive treatment of oligometastasis in the liver in recurrent nasopharyngeal carcinoma

Objective: The principle of management of patients with oligometastasis is evolving. The current study aims to investigate the efficacy of percutaneous radiofrequency ablation (RFA) of the solitary liver metastasis after previous radiotherapy for nasopharyngeal carcinoma (NPC). Methods: A pilot study involving 4 patients with biopsy proven solitary liver metastasis from NPC. After creation of artificial ascites, cooltip RFA needle was inserted into the intra-hepatic tumour under ultrasound guidance. Procedure related complications were noted and patients were followed up regularly and indefinitely for oncological outcome. Results: All patients had locoregionally advanced NPC at initial diagnosis and were treated with concurrent chemoradiation. Complete response was achieved in all patients. The mean time to tumour recurrence was 21.3 months. The mean size of the liver tumour was 3.5cm. Two patients had synchronous local tumour recurrence, and they underwent nasopharyngectomy and neck dissection before receiving treatment to the liver. Percutaneous RFA was performed in all patients. The mean hospital stay was 2.2 days and no procedure related complications were detected. No systemic treatment was given afterwards. The mean follow-up interval was 40.5 months. One of the patients developed progression of disease and died at 13 months after RFA, while the rest of the patients were alive and remained disease free at the last follow-up. Conclusion: Percutaneous RFA is potentially useful as a minimally invasive procedure for patients with solitary liver metastasis after radiotherapy for NPC. Further study is required to confirm its efficacy and to define the protocol of adjuvant systemic chemotherapy to improve the treatment outcome.

The role of adjuvant chemotherapy for lymph node-positive upper tract urothelial carcinoma following radical nephroureterectomy: a retrospective study.

To evaluate the effect of adjuvant chemotherapy (AC) on mortality after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC) with positive lymph nodes (LNs) and to identify patient subgroups that are most likely to benefit from AC. We retrospectively analysed data of 263 patients with LN-positive UTUC, who underwent full surgical resection. In all, 107 patients (41%) received three to six cycles of AC, while 156 (59.3%) were treated with RNU alone. UTUC-related mortality was evaluated using competing-risks regression models. In all patients (T(all) N+), administration of AC had no significant impact on UTUC-related mortality on univariable (P = 0.49) and multivariable (P = 0.11) analysis. Further stratified analyses showed that only N+ patients with pT3-4 disease benefited from AC. In this subgroup, AC reduced UTUC-related mortality by 34% (P = 0.019). The absolute difference in mortality was 10% after the first year and increased to 23% after 5 years. On multivariable analysis, administration of AC was associated with significantly reduced UTUC-related mortality (subhazard ratio 0.67, P = 0.022). Limitations of this study are the retrospective non-randomised design, selection bias, absence of a central pathological review and different AC protocols. AC seems to reduce mortality in patients with pT3-4 LN-positive UTUC after RNU. This subgroup of LN-positive patients could serve as target population for an AC prospective randomised trial.

Time to adjuvant chemotherapy (TTAC) after open or laparoscopic resection surgeries in colorectal cancers (CRC).

768 Background: This single institution retrospective study evaluates the reason for delay in Time To Adjuvant Chemotherapy (TTAC) from curative resection surgery to start of adjuvant therapy in CRC. The reason for this study was to determine if type of surgery (laparoscopic versus open) increased TTAC of which evidence indicates poorer disease free survival and overall survival (Biagi J, Raphael M, Mackillop W, Kong W, King W, Booth C. Association between time to initiation of adjuvant chemotherapy and survival in colorectal cancer: a systematic review and meta-analysis. JAMA, 305(22):2335-42. doi: 10.1001/jama.2011.749.) Methods: CRC patients treated at St. Michael’s Hospital in Toronto, Canada were included if diagnosed with stage II or III disease, underwent curative resection surgery between January 1, 2006, and December 31, 2012, and either received systemic adjuvant chemotherapy or surveillance protocol. Results: Among 259 patients, 92 patients (35.7%) underwent curative laparoscopic resection and 166 open resection (64.3%). Intraoperative and/or postoperative complications were experienced in 73 patients. Complications were less prevalent among patients who underwent laparoscopic surgery versus open resection (11.9% vs. 36.8%; p<0.0001). Of these 73 complications, wound infection (39.7%), intraoperative procedural complication (14.3%), and postoperative gastrointestinal complications (6.4%) were most prevalent. After adjusting for complication and clustering within the operating surgeon, there were no statistical differences in TTAC between open (51.310 ± 1.7 days) and laparoscopic (49.2 ± 1.6 days) resection surgeries (p=0.1996). However, presence of a complication was associated with delay in TTAC (HR 0.501; 95% CI, 0.43-0.58; p<0.001). Conclusions: TTAC in CRC patients does not differ statically for each type of resection surgery. However, presence of a complication is associated with delays in TTAC and is over three-fold more prevalent in open than laparoscopic resections. Therefore, there is an increased risk of delay in TTAC for open resection surgeries than laparoscopic resections due to a higher prevalence of surgical complications.

Neoadjuvant/adjuvant treatment of high-risk retinoblastoma: a report from the German Retinoblastoma Referral Centre

BackgroundRetinoblastoma can extend beyond the structures of the eye, where cells can enter the bloodstream and cause metastases. Various types of protocols for adjuvant treatment risk-adapted according to histopathological risk...