Pre Chemotherapy Research Articles

MiR-371a-3p Predicting Viable Tumor in Patients Undergoing Retroperitoneal Lymph Node Dissection for Metastatic Testicular Cancer: The SWENOTECA-MIR Study.

The SWENOTECA-MIR prospective multicenter study aims to assess the clinical value of miR-371a-3p as a novel marker in metastatic germ cell tumor patients undergoing retroperitoneal lymph node dissection (RPLND), to predict the presence of viable residual tumor. A total of 114 patients (86 nonseminomas, 28 seminomas) who underwent surgery for presumed metastatic disease pre chemotherapy (primary RPLND) and post chemotherapy RPLND were included. The expression of miR-371a-3p was evaluated using reverse transcription-digital droplet polymerase chain reaction before and after RPLND. Pre- and postoperative miR-371a-3p levels were statistically compared, and optimism-corrected performance calculations compared with conventional serum tumor markers. Associations were evaluated by logistic regression. Patients who underwent primary RPLND were categorized into seminoma and nonseminoma groups. Among the seminoma patients (n = 24) undergoing primary RPLND, all had normal conventional markers. Six patients received adjuvant treatment before surgery. miR-371a-3p exhibited a sensitivity of 74%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 21% for viable tumor. The levels of miR-371a-3p significantly decreased after surgery. In the nonseminoma group (n = 18) treated with primary RPLND, 22% had elevated conventional markers and 3 had received prior adjuvant treatment. miR-371a-3p showed a sensitivity of 34%, specificity of 88%, positive predictive value of 67%, and negative predictive value of 62% for the primary nonseminoma patients. No association was observed between stage or prior adjuvant treatment and the outcome of the miR test. In the postchemotherapy group (n = 72), the miR-371a-3p sensitivity was 9%, reducing to 0 when excluding patients with seminoma (n = 4). Teratomas and benign histology were essentially negative. Our study highlights miR-371a-3p as a fairly sensitive and highly specific marker for prechemotherapy seminomas, outperforming conventional markers. However, in prechemotherapy nonseminomas as well as in postchemotherapy patients, we observed low sensitivity and no significant differences in miR-371a-3p levels before and after surgery, suggesting limited utility for miR-371a-3p in this context.

A dynamic microRNA profile that tracks a chemotherapy resistance phenotype in osteosarcoma. Implications for novel therapeutics.

Osteosarcoma is a rare primary bone tumor for which no significant therapeutic advancement has been made since the late 1980s despite ongoing efforts. Overall, the five-year survival rate remains about 65%, and is much lower in patients with tumors unresponsive to methotrexate, doxorubicin, and cisplatin therapy. Genetic studies have not revealed actionable drug targets, but our group, and others, have reported that epigenomic biomarkers, including regulatory RNAs, may be useful prognostic tools for osteosarcoma. We tested if microRNA (miRNA) transcriptional patterns mark the transition from a chemotherapy sensitive to resistant tumor phenotype. Small RNA sequencing was performed using 14 patient matched pre-chemotherapy biopsy and post-chemotherapy resection high-grade osteosarcoma frozen tumor samples. Independently, small RNA sequencing was performed using 14 patient matched biopsy and resection samples from untreated tumors. Separately, miRNA specific Illumina DASL arrays were used to assay an independent cohort of 65 pre-chemotherapy biopsy and 26 patient matched post-chemotherapy resection formalin fixed paraffin embedded (FFPE) tumor samples. mRNA specific Illumina DASL arrays were used to profile 37 pre-chemotherapy biopsy and five post-chemotherapy resection FFPE samples, all of which were also used for Illumina DASL miRNA profiling. The National Cancer Institute Therapeutically Applicable Research to Generate Effective Treatments dataset, including PCR based miRNA profiling and RNA-seq data for 86 and 93 pre-chemotherapy tumor samples, respectively, was also used. Paired differential expression testing revealed a profile of 17 miRNAs with significantly different transcriptional levels following chemotherapy. Genes targeted by the miRNAs were differentially expressed following chemotherapy, suggesting the miRNAs may regulate transcriptional networks. Finally, an in vitro pharmacogenomic screen using miRNAs and their target transcripts predicted response to a set of candidate small molecule therapeutics which potentially reverse the chemotherapy resistance phenotype and synergize with chemotherapy in otherwise treatment resistant tumors. Importantly, these novel therapeutic targets are distinct from targets identified by a similar pharmacogenomic analysis of previously published prognostic miRNA profiles from pre chemotherapy biopsy specimens.

Fluorine-18 FDG PET/CT and New NIMS Grading System for Chemotherapy Response in Breast Cancer.

Positron emission tomography with computed tomography (PET-CT) using fluorine 18-fluorodeoxyglucose (F-18 FDG) is increasingly used to stage patients with locally advanced breast cancer and for assessing treatment response after neoadjuvant chemotherapy (NACT). The aim of the study was to assess the correlation between PET-CT parameters and pathologic response of breast primary after NACT in breast cancer patients and to devise a grading system called NIMS grading system for response assessment using PET quantitative parameters. 55 patients who underwent F-18 FDG PET-CT before starting the therapy and again after completion of therapy were identified and included in the study. The clinical data and the histopathologic findings were recorded. All the patients received chemotherapy followed by surgery with axillary lymph node dissection. The PET-CT results were interpreted both qualitatively by visual analysis and quantitatively by estimating maximum Standardized uptake values(SUVmax) and other parameters - SUVmean, SUL, SUVBSA, Metabolic tumor volume (MTV) and Total lesion glycolysis (TLG). The sensitivity and specificity of F-18 FDG PET-CT to detect the residual disease after neoadjuvant chemotherapy was 75.6% & 92.8% respectively. Differences between complete response and residual disease were significant for ΔSUVmax(p=0.005), ΔSUVmean(p=0.006), ΔSUL (0.005) and ΔSUVBSA(0.004), while ΔMTV and ΔTLG were not significantly different between the two groups. The new NIMS grading system included scoring of ΔSUVmax, ΔSUVBSA, ΔTLG and ΔMTV on scale of 1 to 4 and correlated well with PERCIST criteria. F-18 FDG PET-CT had a good accuracy in the detection of residual disease after completion of NACT. Pre chemotherapy PET-CT is not adequate to predict the response of primary tumour to chemotherapy. However, changes in the values of various PET-CT parameters are a sensitive tool to assess the response to chemotherapy. The new grading system is easy to use and showed good correlation to PERCIST.

HER3 expression status following systemic chemotherapy treatment in biliary tract cancers.

e16153 Background: Erb-b2 receptor tyrosine kinase 3 (HER3) is frequently overexpressed in a variety of cancers. Activation of HER3 signaling serves an important role in promoting cell proliferation and is associated with chemoresistance. Thus, there is interest in exploring HER3 status of tumors as a potential prognostic and/or therapeutic target. Prior studies have reported HER3 status in various cancers after treatment with chemotherapy (CT). However, HER3 expression profile in biliary tract cancer (BTC) remains unknown. Here, we evaluated HER3 status of patients with BTC post CT. Methods: The medical records of patients (pts) who had been initially diagnosed with BTC and treated at the National Cancer Center Hospital (Tokyo, Japan), between January 2010 and June 2020, were retrospectively analyzed. Pts whose post CT specimens were available were included in this study. Immunohistochemical staining for HER3 was performed using HER3/ErbB3 (D22C5) XP Rabbit mAb (Cell Signaling Technology) as a primary antibody. IHC scoring (0, 1+, 2+, 3+) of membranous staining intensity was performed according to HER2 IHC gastric scoring guideline. Results: A total of 19 pts with BTC, with a median age of 59 (range 44-79) years, had specimens available after post CT and were evaluated for HER3 expression status. HER3 status was 3+ in 10 pts, 2+ in 3 pts, 1+ in 4 pts, and 0 in 2 pts. The specimens were obtained from liver in 17 pts, bone in 1 pt, and omental lymph node in 1 pt. The histological type was adenocarcinoma in all pts, and HER3 status according to primary tumor type is shown in the table below. Fourteen pts were treated with gemcitabine (GEM) plus cisplatin (CDDP), 1 pt with GEM plus CDDP plus S-1, 1 pt with GEM plus S-1 as first-line CT for advanced BTC, and 3 pts with S-1 as an adjuvant treatment. Fifteen pts were biopsied after CT to participate in clinical trial. The remaining 4 obtained specimens after CT during primary surgery or surgery for metastases or for cholangitis. The median overall survival of pts with advanced BTC was 23.6 months in HER3 3+, 17.1 months in HER3 2+, 27.7 months in HER3 1+, and 24.6 months in HER3 0. Four pts had specimens available from pre and post CT, all of which were intrahepatic cholangiocarcinoma with the treatment of GEM plus CDDP. HER3 status was upregulated in 3 pts (1 pt 1+ to 2+, 2 pts 2+ to 3+) and downregulated in 1 pt (1+ to 0) at post CT. Conclusions: HER3 expression (1+, 2+, 3+) was observed in 89.5% of previously treated pts with BTC, and HER3 status was upregulated after CT in some pts. These results suggest that HER3 might be a potential therapeutic target in BTC post CT. [Table: see text]

Hubungan antara Ekspresi Heat Shock Protein-70 (HSP70) dengan Skor Risk of Ovarian Cancer Relapse (ROVAR) pada Pasien Kanker Ovarium Epitelial yang Dilakukan Operasi dan Dilanjutkan dengan Kemoterapi

Background: Ovarian cancer is one of the leading causes of death in gynecological malignancies which occupies the third place in the world. One of largest challenge in epithelial ovarian cancer therapy is resistance to chemotherapy. Increased of Heat Shock Protein-70 (HSP70) expression associated with the progressivity of tumor cells growth through the resistance process against chemotherapy, whereas Risk Of Ovarian Cancer Relapse (ROVAR) score is a tool that used to predict the ovarian cancer recurrence risk in patient who underwent surgery followed by chemotherapy.Objective: This study is aimed to evaluate the correlation between HSP70 expression and ROVAR score in patient with epithelial ovarian cancer who underwent first line therapy. Method: This is a retrospective cohort study that involve 42 subjects with epithelial ovarian cancer who had been through surgery (optimal or suboptimal surgery) followed by chemotherapy. Immunohistochemical staining of pre chemotherapy paraffin blocks was performed using HSP70 antibody and recurrence risk was calculated using ROVAR scores after surgery followed by chemotherapy. The external variables evaluated were age, parity, Body Mass Index (BMI), menopause history, and surgical type. Data analysis used Chi Square test, spearman test, and logistic regression analysis.Result and Discussion: Of the total 42 subjects who met the inclusion criteria, most found in advanced stage with the age mean is 54,3 years old. In the ROVAR score measurement, in high risk category is found about 32(76.19%), while in the medium risk and low risk category is 10 (23.81%). On the other hand, strong HSP70 expression was found in 36(85,71%), moderate HSP70 expression in 6(14,39%), and weak HSP70 expression was not found. Based on Spearman's correlative test, there was a positive, very strong, and significant correlation between the expression of HSP70 and risk allocation according to ROVAR score (r=0.717, p=0.000). As well as in multivariate analysis, HSP70 expression had a statistically and clinically significant relationship with ROVAR score (p=0.017; RR 2.710; 95% CI 0.366-5.054) which strong HSP70 expression was 2.71 times more likely to have a high risk of recurrence according to ROVAR score.Conclusion: There is a positive, very strong, and significantly meaning between HSP70 expression and ROVAR score. Increased in HSP70 expression may lead to increased recurrence risk according to ROVAR score. Both could be used to predict recurrence in epithelial ovarian cancer post first line therapy.Keywords: Epithelial ovarian cancer, HSP70, ROVAR score, recurrence.

P-021: Experience with autologous stem-cell transplant (auto-SCT) in patients with systemic light-chain amyloidosis (LA) at our center

<h3>Background</h3> Auto-SCT is the standard first-line treatment in patients with LA and good personal status. This procedure achieves haematological responses >70% with an average survival rate of more than 8 years. Depending on patient characteristics and hospital guidelines, prior chemotherapy (CT) is administered, usually with Bortezomib-based regimens. The main determinant of survival in LA is cardiac involvement. The subgroup of patients with cardiac involvement and an indication for Auto-SCT is at the highest risk of complications and mortality and should therefore be strictly selected. <h3>Objective</h3> Our objective is to review the experience in our center with Auto-SCT in patients with LA. <h3>Methods</h3> A retrospective descriptive study was conducted at the Son Espases University Hospital between November 2012 and June 2021. Pre- and post-SCT clinical-biological data, complications during transplantation and progression-free survival (PFS) were analyzed. <h3>Results</h3> Eleven patients with a median age of 59 years at the time of Auto-SCT (range 41-69) were included, of whom 7 were male (64%). Ten patients (90.9%) had renal involvement at diagnosis and 6 (54.5%) had cardiac involvement. According to the Mayo Clinic 2013 prognostic staging score, 6 patients (54.5%) had stage I, 3 patients (27.3%) had stage II and 2 patients (18.2%) had stage IIIb (18.2%). All patients received pre Auto-SCT CT with bortezomib-based regimens. The median pre Auto-SCT left ventricular ejection fraction was 58% (41-79 range). Pre Auto-SCT organ-based chemotherapy response was: 8/10 patients (80%) with renal response; 1/6 patients (16.7%) with cardiac response. Pre Auto-SCT haematological response was: 7 patients (63.6%) complete remission, 1 patient (9%) very good partial response, 1 patient (9%) partial response, 1 patient (9%) stable disease and 1 patient (9%) not assessable. The median number of CD34+ cells infused into Auto-SCT was 3.66×10⁶/kg. 10 patients (90.9%) received G-CSF from day +5. 10 patients (90.9%) developed complications during transplantation, 7 of them requiring admission to the Intensive Care Unit (ICU) with a median of 15 days of admission (range 1-24 days), mainly due to acute pulmonary edema - APE (85.7%). 3/7 patients requiring ICU admission passed away, leaving the Auto-SCT-related mortality rate at 27.3%. With a median follow-up of 36 months (range 5-90), a median PFS and an overall survival rate (OS) of 73% (95%CI 46-99) is observed. PFS and OS match because there are no progression events. <h3>Conclusions</h3> Patients with cardiac involvement prior to Auto-SCT have a high risk of morbidity and mortality, with APE being the main complication in our study. Multidisciplinary management of these patients during Auto-SCT is essential to avoid complications.

Desmoplastic small round cell tumor: A series of patients surgically treated at a single institution.

e23555 Background: Desmoplastic small round cell tumor (DSRCT) is an ultra rare sarcoma predominantly involving the abdomino-pelvic peritoneum and mostly occurring in male children and young adults. It is marked by the EWSR1-WT1 fusion gene. Prognosis is poor with reported 5-year overall of &lt; 20%. Methods: Data of patients with primary intra-abdominal DSRCT, who had surgery at our institution between 2000 and 2020, were analyzed. Information regarding disease presentation, cytoreductive surgery (CRS) with or without hypertermic intraperitoneal chemotherapy (HIPEC) and perioperative treatments were reported. Kaplan-Meier survival analysis was performed for both the whole cohort (A) and separately for peritoneal (B) vs peritoneal + lymphnode involvement (C) at disease presentation. Also, patients who underwent CRS alone vs CRS + HIPEC were compared. Results: 43 patients (pts) were identified, only 18 (42%) underwent surgical resection with curative intent in addition to perioperative chemotherapy (CT) ± radiotherapy (RT). 6 pts had also synchronous abdominal nodal metastases and one resectable liver metastases. Median tumor size was 19cm (12-20). 9 pts received pre and postoperative chemotherapy (CT), 7 pts preoperative CT, 2 pts postoperative CT. Postoperative abdominal RT was administered in 3 pts. Partial response (PR) to preoperative CT was observed in more than 50% of pts. Complete cytoreduction was achieved in 14 pts (78%). HIPEC was performed in 5 patients (28%). Overall, 8 pts died (44%), 1 patient after developing liver and lung metastases while 7 had peritoneal and intra-abdominal lymphnode recurrence. Of 10 patients alive, 7 had a recurrence. Of them, 5 are alive with disease (1 presenting extra-abdominal recurrence, 3 lymph node involvement and 1 liver metastases) at 75, 38, 33, 15 and 31 months, respectively, from diagnosis. 2 are alive without disease (after having a further surgery for local recurrence) at 35 and 36 months, respectively, from diagnosis. 3 patients are alive without disease at 12, 64, and 213 months from diagnosis. As a result, 5-year OS was 39.6%, 35.6% and 40% for group A, B and C, respectively. Median survival time was 39.2, 39.2 and 57.7 months for group A, B and C, respectively. 5-year OS was 35.2% and 50% for CRS and CRS + HIPEC group respectively. Conclusions: Despite an intense multimodal approach, DSRCT prognosis remains poor. CRS may improve oncologic outcomes. Our data confirmed significant tumor shrinkage after administration of preoperative CT which may be helpful to achieve macroscopically complete resections. The value of HIPEC and radiation therapy is more controversial and needs to be further investigated in a larger series. Interestingly, the presence of synchronous nodal metastases was not a negative survival prognosticator showing comparable outcome to peritoneal disease.

Serum Malondialdehyde as a Biomarker of Oxidative Stress in Patients with Primary Ocular Carcinoma: Impact on Response to Chemotherapy.

PurposeTo study the level of serum malondialdehyde (MDA), a biomarker of oxidative stress before and after chemotherapy in various ocular malignancies and to correlate its significance with clinicopathological parameters.MethodsThirty two histopathologically confirmed cases of primary ocular malignancies were included in this longitudinal cohort study. Detailed clinicopathological assessment was done. Analysis of serum MDA level in the patient before and after chemotherapy was measured and its prognostic significance was analyzed.ResultsMaximum cases were of eyelid malignancy (n=18, 56.2%) followed by retinoblastoma (18.8%) and OSSN (6, 18.8%). About 43.75% patients were in the advanced-stage. The tumor was histopathologically well-differentiated in 20 (62.5%) cases. Most common malignancy was sebaceous gland carcinoma of the eyelid (n=10,31.25%). Serum MDA level in patients were significantly higher than controls [5.5712±0.32779 vs 2.5531±0.08056 nmol/mL, p<0.001]. Level was significantly reduced after chemotherapy (4.5146±0.23209 nmol/mL). Serum MDA was maximum in cases of rhabdomyosarcoma (5.9450±0.23335 nmol/mL) and retinoblastoma (5.7433±0.14334 nmol/mL). It was minimum in basal cell carcinoma (5.3775±0.17746 nmol/mL). Pre chemotherapy serum MDA level was significantly higher in patients having larger tumor (>20mm, p< 0.001) and having lymph node metastasis than those without lymph node metastasis [5.8350±0.17113 vs 5.4833± 0.32193 nmol/mL, p<0.006]. No significant difference was observed in post chemotherapy serum MDA level as for as size of tumor (p=0.947) and histopathological differentiation (p=0.109) was concerned.ConclusionThe serum MDA level is a potential biomarker in primary ocular carcinoma to assess oxidative stress and its impact on response to chemotherapy.

Novel 2 Marker Sandwich Immunoassay for the Detection of Precursor- and Mature Granulocyte-Derived Exosomes in Peripheral Blood: A Preliminary Case Study

Introduction: In order to assess hematopoietic precursor cells, bone marrow biopsies are routinely conducted, which is painful for the patient and is not applicable for frequent testing. However, precursor, maturating, and matured cells are known to produce exosomes, which are released into peripheral blood. By analyzing these exosomes in plasma, bone marrow condition may be assessed noninvasively. Myeloid precursor cells express different surface markers than when they have matured. It is reasonable to speculate that these markers would be incorporated into exosomes. In this study, we developed a novel sandwich enzyme-linked immunosorbent assay (ELISA) by using a combination of monoclonal antibodies against 2 different leukocyte antigens, to account for the number of exosomes in plasma. Methods In 6 patients undergoing chemotherapy, venous blood was drawn at regular intervals before, during, and after respective chemotherapies was given. Various clones of monoclonal antibodies against CD11b, CD33, CD34, CD35, CD81, and CD117 were obtained, and antibodies were biotinylated by EZ link Sulfo-NHS-LC-Biotin. Anti-brain antibodies were switched with anti-leukocyte antibodies, and exosome activity was trended. Results CD11b+ and CD 117+ plates showed small changes during chemotherapy (within +/- 50% of the initial value), while plasma WBC count showed a dramatic decrease during chemotherapy. In the recovery phase of WBC after chemotherapy, CD11b+ and CD16+showed a greater than 2-fold increase, with the up-trend taking place earlier than its plasma WBC counterparts. CD 117+ CD33+ also showed an up-trend, but was slower than their CD11b+ and CD16+ counterpart. Finally, each exosome value was divided by other markers to calculate the ratio, and compared between pre and post chemotherapy blood. In half of the cases, there was not a difference, versus an almost double premature/mature ratio in post-chemotherapy blood in the other half of patients. Conclusion From data collected from pre-chemotherapy studies, the lack of correlation between ELISA data compared to plasma WBC data, indicates that plasma exosome analysis might not be suitable for the monitoring of acute bone marrow suppression. Additionally, in the recovery phase, surface markers correlation with WBC was present in only some of the markers, indicating that the assay sensitivity is dependent on the marker combinations. Overall, both myeloid precursor- and mature granulocyte-derived exosomes were increased during the recovery from chemotherapy in 3 out of 5 patients, and exosome profiles were different after chemotherapy in 2 out of 5 patients. Disclosures Mitsuhash: NanoSomiX:Current Employment.

The role of cardio-protective agents in breast cancer patients to prevent anthracycline induced cardiotoxicity: a systematic review and network meta-analysis

Abstract Background Anthracycline (ANT)-based chemotherapy for breast malignancies have significantly improved cancer outcomes. However, the cardiotoxicity induced by ANTs in the breast cancer population has increased major adverse cardiac events. While randomised controlled trials (RCTs) have explored different primary preventative agents to confer cardio-protection pre chemotherapy, comparisons between agents has been limited. It is unclear which drug is the most efficacious in preserving Left Ventricular Ejection Fraction (LVEF) amongst this population. Purpose To perform a network meta-analysis of RCTs comparing the impact on LVEF of various prophylactic cardio-protective agents, when prescribed to breast cancer patients prior to ANT-based chemotherapy. Methods Two independent authors performed a literature search as per the PRISMA guidelines using four databases (CENTRAL, Cochrane Reviews, MEDLINE, SCOPUS), to find RCTS evaluating cardio protective agents. The trial population was limited to patients with breast cancer without prior ANT exposure. Trials were only included if the cardio-protective agents were commenced prior to ANT dosing. The assessed outcome was a mean change in LVEF pre and post ANT dosing, compared to placebo prevention. Extracted data included age, ANT dose, and LVEF pre and post chemotherapy. The Cochrane Risk of Bias tool was used to appraise included RCTs. Results From 2807 search results, we identified twelve RCTs which evaluated 1126 patients. Seven studies assessed beta-blockers alone and two assessed combination ACE inhibitors and beta blockers. Individual studies assessing ACE inhibitors, spironolactone or rosuvastatin alone were also included. All patients were female with an average age of 50.5 and average ANT dose of 412 mg/m2. Our network meta-analysis showed beta-blockers showed significant protection with higher LVEF than placebo by 2.38% [0.52, 4.25]. ACE inhibitors showed a similar magnitude of LVEF preservation 2.59% [−0.20, 5.38] but not statistically significant due to wider CI because of lower sample size (n=250). Spironolactone showed a statistically significant preservation in LVEF by 12.80% [3.44, 22.16], however this was based on a single study (n=83), with marked measurement bias and deviations from intended intervention. All included trials had an intermediate or high risk of bias, with marked heterogeneity in ANT dosing and LVEF monitoring. Conclusion Beta-blockers minimise LVEF decline when administered prior to anthracycline chemotherapy, compared against alternate agents. Data may be underpowered to demonstrate the benefit of ACE inhibitor and combination beta blocker/ACE inhibitor prescription. The quality of RCT data to date is limited by a high risk of bias and significant heterogeneity between RCA reporting. This analysis is likely to inform clinical practice, and allow clinicians to prescribe primary cardio-protection in patients at high risk of cardiotoxicity. Funding Acknowledgement Type of funding source: None

A study of anti-oxidant levels pre and post induction chemotherapy in children with acute lymphoblastic leukemia

A study of anti-oxidant levels pre and post induction chemotherapy in children with acute lymphoblastic leukemia

RATIO OF SERUM CA125 TO RADIOLOGICAL PERITONEAL CARCINOMATOUS INDEX AS A NOVEL MARKER OF RESPONSE TO NEO ADJUVANT CHEMOTHERAPY AND PREDICTIVE MODEL OF SURGICAL OUTCOME IN ADVANCED EPITHELIAL OVARIAN CANCER- A SINGLE INSTITUITIONAL STUDY.

Objective: The objective of this retrospective study is to develop a novel marker- ratio of serum CA 125 to peritoneal carcinomatous index(PCI) - to predict the response in women receiving neoadjuvant chemotherapy for newly diagnosed advanced epithelial ovarian cancer at our centre. Methods: Medical records of women who were newly diagnosed with inoperable advanced ovarian cancer stages III and IV at our centre were selected. Only people with completely documented records in the years 2017 &amp; 2018 were selected. Only patietns with serous histology were chosen. Pre chemotherapy serum CA125 value was noted. Radiological PCI was calculated by reviewing the CECT films &amp; reports of the patients. Patients were compared with the ratio of CA125 to radiological PCI and clinical &amp; pathological response to neo adjuvant chemotherapy. All patients received standard doses of three weekly Paclitaxel and Carboplatin based chemotherapy. Based on the ratio of CA125 to PCI patients were divided into 2 groups – ratio more than 100 and less than 100. Results: A total of 34 were patients were found to meet the eligible criteria. Response assessment was done after 3 to 4 cycles of neoadjuvant chemotherapy. The overall response rate to neoadjuvant chemotherapy in patients in group 1 ( CA125/PCI ratio &gt; 100) was significantly higher as compared to patients in group 2 (CA125/PCI ratio &lt;100). Conclusion: In summary, CA 125 to PCI ratio is novel method to predict response to chemotherapy in advanced epithelial ovarian cancers. This value is a helpful measurement that allows the clinicians to measure the degree of chemosensitivity prior to cytoreductive surgery. This measures the inherent tumor biology and to aids in surgical decision making regarding the role and extent of cytoreduction as well as alternate systemic/local therapies.

Clinical outcomes of patients with gastric cancer according to pre and post-neoadjuvant chemotherapy PD-L1 immunohistochemistry (IHC) expression.

e16569 Background: The incidence, prognostic and predictive impacts of PD-L1 expression in locally advanced gastric cancer is unknown. We aimed to determine the expression of PD-L1 by CPS in the pre-treatment biopsy and surgical specimens of patients (pts) with gastric cancer who received neoadjuvant therapy and its association with pathological response and survival outcomes. Methods: Retrospective cohort of pts treated at a cancer center from 2007 to 2017. Pts with confirmed gastric or GEJ adenocarcinoma who received neoadjuvant treatment and curative-intent D2 surgery were included. Gastric stump tumors and those who had a total esophagectomy were excluded. Clinical data were obtained from medical charts. Biopsy samples and a tissue microarray with the most representative areas of the surgical specimen were used to detect PD-L1 IHC expression with 22C3 phamDx antibody. Results were analyzed using the CPS score. Overall and DFS survival included the Kaplan-Meier product-limit estimator in an ITT analysis and a Cox regression was used to obtain crude and adjusted HR for prognostic factors. Results: 270 pts were included: median age was 58.9 years, most (51.5%) had cT3-T4N+ stages, 45% had diffuse histology and 87.8% completed the preoperative regimen. 13% had a pCR, while 53% had minimal tumor regression. With a median follow-up of 60.3 months (CI 95% 54.7 – 65.8), the median OS and DFS were not reached. 11.4% of biopsies and 18.6% of surgical specimens had positive CPS, with a median score of 3 (IQR 2,0 – 7,5) and 9 (IQR 5.0 – 20.0) respectively. In 18.9% of paired samples the PD-L1 expression was found to be negative in the biopsy sample and positive in the surgical specimen. PD-L1 expression was neither associated with pathologic response after neoadjuvant chemotherapy, nor with survival outcomes. Conclusions: PD-L1 expression on the setting of locally advanced gastric cancer was low and it was different when biopsy and surgical specimens were compared. No impact on survival results could be detected. [Table: see text]

PD19-06 LOCATION AND HISTOLOGY OF RETROPERITONEAL METASTASES IN POST-CHEMOTHERAPY RETROPERITONEAL LYMPH NODE DISSECTION FOR NON-SEMINOMA GERM CELL TUMOUR

INTRODUCTION AND OBJECTIVE: Post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND) in patients with metastatic non-seminoma germ cell tumour (NSGCT) is a procedure with high complication rate and risk of permanent retrograde ejaculation. The current Swedish and Norwegian Testicular Cancer Group (SWENOTECA) modified unilateral template results in a low complication rate, but a relatively high proportion of patients experiences permanent retrograde ejaculation. The objective was to evaluate the histology of the resected nodes in specific areas and outcome of patients, to identify which patients that safely could benefit from a more restricted unilateral template without resection on the contralateral side of the aorta. METHODS: All NSGCT patients within the SWENOTECA network with post-chemotherapy residual tumour of 10-50mm in the largest axial diameter, treated with PC-RPLND between 2007 and 2014 were evaluated in this prospective population-based study. A modified unilateral PC-RPLND could be selected in patients with residual tumour located in the template of a unilateral PC-RPLND (areas 1-5,7,9 for a right-sided NSGCT and 2,3,6,8,10 for a left-sided NSGCT). Laterality of the testicular NSGCT, location of pathological lymph nodes on the CT scan pre chemotherapy and pre-PC-RPLND, areas dissected and the histology for each area was recorded. Follow-up until end of 2016. RESULTS: There were 113 right and 107 left-sided NSGCT. A black dot represents each patient in each area with a postitive node pre-chemotherapy and pre-PC-RPLND, if the area was dissected and teratoma/cancer at histology was found. A red dot represents each patient with negative nodes pre-PC-RPLND and teratoma/cancer was found. In right-sided and left-sided NSGCT respectively 4/6 and 4/5 patients that had a red dot in a contralateral area of the aorta, had positive nodes on CT in an other contralateral area. During follow-up of median 69 months, 4 patients had an in-field recurrence CONCLUSIONS: If the residual mass is located in the unilateral template of the affected testicle (areas 1,2,4,5,7,9 for a right-sided NSGCT and areas 3,6,8,10 for a left-sided NSGCT) and residual tumour size is 10-50mm, a unilateral template is sufficient to remove all teratoma/vital cancer. If the pre or post chemotherapy CT scan shows a pathological lymph node outside of a unilateral template an extended template is recommendedSource of Funding: none

Chemotherapy Effect on Fertility in Male Patients with Hodgkin and Non-Hodgkin Lymphoma

Introduction: The chemotherapeutic agents are effective in destroying cancerous cells for patient with hematological malignancies, but can damage the germinal cells. Hence, the infertility is the therapy-induced complication, which can be transient or permanent, depending on type of treatment protocol used and other factors. The aim of the study was to assess the fertility status among patients treated for Hodgkin lymphoma (HL) and Non-Hodgkin lymphoma (NHL). Methods: A chart review was done for patients followed up in hematology clinic. All male patients treated for hematological malignancies during the period from 2004-2014 were assessed. The infertility status was assessed using WHO infertility criteria. The fertility status was defined based on semen analysis or having a child post chemotherapy. The data was captured for type of protocol, number of cycles, fertility status, having a child pre and post chemotherapy, and sperm bank utilization. Results were summarized as frequency and percentages. Data was analyzed using SAS. Results: 400 medical charts were reviewed. 208/400 were included based on age inclusion criteria (18-60 years). 59/208 included based on available fertility data, of which 31 were diagnosed with HL, 21 NHL, 4 acute lymphocytic leukemia, and 3 acute myeloid leukemia. Only HL and NHL were considered for further analysis. 9/31 (29%) with HL and 1/21 (4.7%) with NHL had infertility prior to starting chemotherapy based on semen analysis with no follow-up fertility assessment done post-treatment. The final sample consisted of 42 patients who had data available on their fertility status post-treatment (22 HL and 20 NHL) (Figure 1). The mean age was 38 ± 8 years. 25(68%) had advanced disease. Among HL, 8/22 (36.36%) were fertile (7 conceived a child and 1 with normal semen analysis) (Figure 2). This includes 6 out of 9 (66.7%) patients who received ABVD protocol alone, 0 out of 6 who received ABVD + BEACOPP protocol, and 2 (28.6%) out of 7 who received salvage chemotherapy. Among the NHL, 11/20 (55%) were fertile (8 conceived a child and 3 with normal semen analysis) (Figure 2). This includes 7 out of 11 (63.6%) who received CHOP +/-Rituximab protocol, 3 out of 5 (60%) who received CHOP + other chemotherapy (MTX/CVP), 1 out of 3 (33.3%) who received only other chemotherapies (Hyper CVAD/MTX) (Figure 2). 9 out of 22( 41%) HL and 6 out of 20 NHL patients had sperm banking done, and only two utilized their sperms with one successful conception in a patient with NHL (Figure 3). Conclusion: Although the sample size is very small, we found a trend that may suggest HL to affect fertility and that ABVD protocol may not be as safe as it thought to be on fertility. The advanced stage of the disease being the majority may have influenced this finding. We found the documentation of fertility status among patients receiving chemotherapy to be scarce. Hence, it is important to educate physicians and dedicate a protocol for assessment of fertility pre- and post-treatment with encouragement to utilize sperm banking. Disclosures No relevant conflicts of interest to declare.

300P - Outcome of triple negative inflammatory breast cancers (TNIBC) treated with dose dense neoadjuvant epirubicin cyclophosphmide, prognostic impact of pre and post neoadjuvant chemotherapy (NAC) tumour infiltrating lymphocytes (TIL) and post NAC lymphovascular invasion

BackgroundInflammatory breast cancers (IBC) particularly triple negative (TN) subtype have poor prognosis. MethodsBetween January 2010 and December 2016, all patients with TNIBC seen at breast cancer disease center, St Louis hospital, Paris, France, were treated with neoadjuvant dose dense Cyclophophamide (1.2g/m2 d1) - Epirubicin (75mg/m2 d1) q2w (SIM regimen) followed with 12 injections of paclitaxel (80mg/m2) qw or 4 injections of docetaxel (100mg/m2) q3w. All patients have histologically proven TN tumors and no evidence of metastases. Mastectomy and axillary clearance was performed after chemotherapy. pCR was defined as no residual invasive tumor in breast and lymph nodes. TIL and lymphovascular invasion were evaluated pre and post NAC by 2 independent anatomopathologists dedicated to breast cancer. Delta TIL was defined as the difference between post chemotherapy and pre chemotherapy TIL. ResultsThirty TNIBC patients were treated, 28 underwent surgery and 2 progressed during chemotherapy. Median follow-up was 45 months (8 – 103). 9/30 patients (30%) achieved pCR. Median disease free survival was not reached. Median TIL infiltration at diagnosis was 11% (0-60) and dropped to 1% after chemotherapy (0 – 80). On univariate analysis, LVI after chemotherapy (HR=2.1 [95% CI, 1.1–3.6], p=0.02), TIL on mastectomy (HR=1.8 [95% CI, 1.1–3.1], p=0.03), delta TIL (HR=2.2 [95% CI, 1.4–3.5], p=0,001) were associated with DFS but no pCR (p=0,051). On multivariate analysis, only delta TIL remainedstatistically significant (HR=1.9 [95% CI, 1.1–3.4], p=0.03). ConclusionsWe showed in this retrospective series of 30 TNIBC that dose dense dose intense chemotherapy is efficient in this population. Delta TIL is a strong prognostic factor associated with DFS. We show that a positive Delta TILis, among others, a strong and independent predictor of DFS: in TNIBC contrary to the results obtained in TN non inflammatory breast cancers, an increase in TIL after chemotherapy is associated with a decrease in DFS.The exact impact of LVI must be further investigated. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

Impact of prechemotherapy preparation on knowledge, coping attitude and satisfaction among newly diagnosed patients with cancer

Objective: Cancer’s patients receiving chemotherapy need information about the treatments and self-care that must practice in order to prevent serious complications. Purpose of the study: To determine the impact of prechemotherapy preparation on knowledge, coping attitude and satisfaction among newly diagnosed patients with cancer.Methods: Quasi experimental research design was used. The study was conducted at outpatient’s chemotherapy clinic and at word of the Oncology Menoufia University Hospital, Shebin El-Kom, Egypt. A convenience sample of 100 adult patients of both sexes who were diagnosed with cancer in the Oncology outpatient clinic and would receive first time chemotherapy treatment were enrolled in this study. Three tools were used. Tool I: Chemotherapy Patients needs assessment: structured interviewing scheduled questionnaire: The tool consisted of the following 2 parts. Part 1: Sociodemographic and clinical data, Part II: Pre Chemotherapy Knowledge Assessment Sheet. Tool II: 16 attributes of cancer therapy satisfaction questionnaire (CTSQ). Tool III: Cancer Coping Questionnaire (CCQ) 21 Items Versions.Results: The study group had better knowledge, coping and satisfaction post intervention than control group. There was statistically considerable differences between study and control group concerning the mean total score of satisfaction and coping (p value &lt; .001). There were significant positive correlation total score of cancer coping and mean score of cancer therapy satisfaction p value &lt; .001.Conclusions: Prechemotherapy preparation to cancer patients improved patient’s knowledge, satisfaction and coping. Recommendation: Prechemotherapy education should be considered a part of routine nursing care performed for all newly diagnosed patients with cancer who would receive chemotherapy for first time.

Timing of docetaxel chemotherapy and impact on outcomes in metastatic castrate-resistant prostate cancer (MCRPC).

298 Background: Docetaxel use has led to a significant prolongation in overall survival (OS) in metastatic prostate cancer after castrate resistance, with a more substantial OS gain when used in combination with initial androgen deprivation therapy (ADT). There is however limited information on outcomes in patients who initially do not receive chemotherapy, perhaps through patient choice or impaired performance status, who become suitable for docetaxel, comparing earlier with later docetaxel treatment. Methods: We retrospectively reviewed patients’ electronic clinical and prescribing records diagnosed with MCRPC and treated with docetaxel from 01/01/2006 to 24/11/2016 in a single centre in the UK. Data was reviewed for number of individual treatments received pre and post chemotherapy, including initial ADT, enzalutamide, abiraterone, docetaxel, cabazitaxel, mitoxantrone, radium 223, single agent steroids and diethylstilboestrol. Prostate specific antigen (PSA) response, number of cycles and dosing of docetaxel and OS were also reviewed. Results: 168 consecutive patients with MCRPC receiving docetaxel were reviewed. Median Gleason grade across the three groups was 8. 48 patients (29%) received docetaxel after 1 or 2 previous treatments, 105 (63%) after 3 or 4 previous treatments and 15 (9%) after 5 or 6. PSA response rates were superior in the earlier treated group (61%, p=0.003), compared with 30% and 31% respectively in the later groups. Median number of cycles was 5.5 overall, with a mean weighted dose received of 396mg/m2, 373mg/m2 and 301mg/m2 in the after 1 or 2 treatments, after 3 or 4 treatments and after 5 or 6 treatment groups. Median OS from castrate resistance for the earlier group was 29 months, not significantly less (p=0.1) than the 35 months for an intermediate number of prior treatments and 42 months for the later treated group. Conclusions: In this group of patients in routine clinical practice who do not receive docetaxel with initial ADT, PSA response rates are significantly improved and overall dose received is higher with subsequent earlier use. However, overall survival is not significantly different between the early and later docetaxel treated patients.

Abstract P3-06-10: Multiscale modeling of omics data for precision breast cancer treatment

Abstract Introduction: The vast majority of cancer patients continue to receive treatments that are minimally informed by omics data. In the case of breast cancer, only ER and HER2 are routinely used for treatment selection. There is a particular need for personalized treatment in individuals with primary and secondary drug resistance or aggressive breast cancers. Emerging bioinformatics and statistical methods have made a fundamental impact on cancer research. However, challenges remains with regard to patient-centric data analysis and providing genomic data guidance to oncologists. There exists a large number of FDA approved anti-neoplastic drugs used to treat cancers other than breast and the development of innovative informatics methods and algorithms to repurpose those drugs should benefit breast cancer patients. Methods and Results: We have developed precision care systems (such as PANOPLY and CORPUS) to identify personalized therapies for an individual patient and to deliver genomic reports in a standard, searchable format so that a researcher or an oncologist can quickly navigate through molecular data and obtain prioritized drugs and targets.The PANOPLY (Precision cancer genomics report: single sample inventory) algorithm applies machine learning and topology-based network analysis methods to integrate multi-omics profiles and clinical data; individual-specific molecular alterations are identified and compared with a set of matched-controls having similar clinical data. Since there is a lack of a “gold standard” dataset to test such algorithms, we simulated 500 case-control sets and evaluated drug predictions across multiple simulation scenarios. We applied the PANOPLY algorithm to The Cancer Genome Atlas (TCGA) breast cancer cohort, which consists of multi-omics data and clinical data. In addition, PANOPLY was also applied to an in-house neoadjuvant breast cancer study (BEAUTY) that consists of multi-omics data, clinical data, and patient-derived xenografts (PDXs). In the TCGA breast cancer study we obtained survival data to determine the cases and matched-controls; and in the BEAUTY, we used pathologic complete response (pCR) as an outcome to determine responders and non-responders. Recurrent targetable alterations were not enriched in patients without pCR in the BEAUTY study. We have applied the PANOPLY to non-responder patients to identify individual specific alterations, dysregulated networks, drug targets, and drugs for each patient and stored them as case reports in CORPUS (Computational Oncology Reports and Precision therapeUticS), a web-based repository that allows clinicians to review genomic reports. Using comprehensive “omic” data derived from a triple negative breast cancer patient who had pre and post-neoadjuvant chemotherapy PDXs, PANOPLY prioritized the PARP inhibitors as the top class of drug. Using the PDX models available from this patient, we tested olaparib and confirmed the in vivo antitumor activity (more effective than vehicle with a p-value &amp;lt; 0.05 in the PDXs). Further studies to confirm PANOPLY findings are currently underway. Conclusions: In summary, the PANOPLY and CORPUS systems incorporate molecular data together with clinical data to provide genomic reports with proposed drug targets to advance or enable precision breast cancer care. Citation Format: Kalari KR, Sinnwell JP, Thompson KJ, Tang X, Carlson EE, Alaparthi T, Yu J, Vedell PT, Kalmbach MT, Bockol MA, Hossain A, Weinshilboum RM, Boughey JC, Wang L, Suman VJ, Goetz MP. Multiscale modeling of omics data for precision breast cancer treatment [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-06-10.

Abstract P5-17-05: Outcome of triple negative inflammatory breast cancer (TNIBC) treated with dose-dense dose intense neoadjuvant chemotherapy (NAC), prognostic impact of post NAC lymphovascular invasion and tumor infiltrating lymphocytes (TIL)

Abstract Background Inflammatory breast cancers (IBC) particularly triple negative (TN) subtype have poor prognosis. There are few series reporting IBC outcome according to their immunohistochemical profile. We have already shown the efficiency of dose dense dose intense chemotherapy in triple negative breast cancer (1). We report a series of TNIBC treated with dose dense anthracycline cyclophosphamide followed with taxane and analyzed the correlation between pathological complete response (pCR), pre and post NAC TIL, post NAC LVI and disease free survival (DFS). Methods Between January 2010 and December 2016, all patients with TNIBC seen at breast cancer disease center, St Louis hospital, Paris, France, were treated with neoadjuvant dose dense dose intense Cyclophophamide (1.2g/m2 d1) - Epirubicin (75mg/m2 d1) q2w (SIM regimen) followed with 12 injections of paclitaxel (80 mg/m2) qw or 4 injections of docetaxel (100 mg/m2) q3w. All patients have histologically proven TN tumors and no evidence of metastases assessed by initial FDG PET Scanner. Mastectomy and axillary clearance was performed after chemotherapy. pCR was defined as no residual invasive tumor in breast and lymph nodes. TIL and lymphovascular invasion were evaluated pre and post NAC by 2 independent anatomopathologists dedicated to breast cancer. Delta TILS was defined as the difference between post chemotherapy and pre chemotherapy TIL. Results Thirty TNIBC pts were treated, 28 underwent surgery and 2 progressed during chemotherapy. Median follow-up was 39 months (8 – 86). 9/30 patients (30%) achieved pCR. Median disease free survival (DFS) was 41 months (2 – 86). Median TIL infiltration at diagnosis was 11% (0-60) and dropped to 1% after chemotherapy (0 – 80). Median delta TIL was - 9% (-50% – +40%). TIL increase after chemotherapy was associated with a decrease of DFS (14 months vs not reached ; p = 0,0009). LVI was present on surgical specimens in 12 cases (12/30, 43%; 12/21 non pCR pts 57 %). Presence of LVI after chemotherapy was significantly associated with a decrease of DFS in the whole population (21 months vs not reached ; p = 0.008) and no significantly among the patients without pCR (23 months vs not reached; p = 0.07). Conclusion To the best of our knowledge, it is the best pCR rate reported in TNIBC (2). We showed in this retrospective series of 30 TNIBC that dose dense dose intense chemotherapy is efficient in this population. Presence of lymphovascular invasion and TIL after neoadjuvant chemotherapy in TNIBC are strong prognostic factors associated with DFS. Systematic determination of post NAC TIL and LIV could be a surrogate to propose adjuvant treatment after NAC in TNIBC.