Independent Oncologists Research Articles

Deep learning promoted target volumes delineation of total marrow and total lymphoid irradiation for accelerated radiotherapy: A multi-institutional study

Background and purposeOne of the current roadblocks to the widespread use of Total Marrow Irradiation (TMI) and Total Marrow and Lymphoid Irradiation (TMLI) is the challenging difficulties in tumor target contouring workflow. This study aims to develop a hybrid neural network model that promotes accurate, automatic, and rapid segmentation of multi-class clinical target volumes. Materials and methodsPatients who underwent TMI and TMLI from January 2018 to May 2022 were included. Two independent oncologists manually contoured eight target volumes for patients on CT images. A novel Dual-Encoder Alignment Network (DEA-Net) was developed and trained using 46 patients from one internal institution and independently evaluated on a total of 39 internal and external patients. Performance was evaluated on accuracy metrics and delineation time. ResultsThe DEA-Net achieved a mean dice similarity coefficient of 90.1 % ± 1.8 % for internal testing dataset (23 patients) and 91.1 % ± 2.5 % for external testing dataset (16 patients). The 95 % Hausdorff distance and average symmetric surface distance were 2.04 ± 0.62 mm and 0.57 ± 0.11 mm for internal testing dataset, and 2.17 ± 0.68 mm, and 0.57 ± 0.20 mm for external testing dataset, respectively, outperforming most of existing state-of-the-art methods. In addition, the automatic segmentation workflow reduced delineation time by 98 % compared to the conventional manual contouring process (mean 173 ± 29 s vs. 12168 ± 1690 s; P < 0.001). Ablation study validate the effectiveness of hybrid structures. ConclusionThe proposed deep learning framework achieved comparable or superior target volume delineation accuracy, significantly accelerating the radiotherapy planning process.

Assessing the utility of molecular diagnostic classification for cancers of unknown primary.

Roughly 5% of metastatic cancers present with uncertain origin, for which molecular classification could influence subsequent management; however, prior studies of molecular diagnostic classifiers have reported mixed results with regard to clinical impact. In this retrospective study, we evaluated the utility of a novel molecular diagnostic classifier by assessing theoretical changes in treatment and additional testing recommendations from oncologists before and after the review of classifier predictions. We retrospectively analyzed de-identified records from 289 patients with a consensus diagnosis of cancer of uncertain/unknown primary (CUP). Two (or three, if adjudication was required) independent oncologists separately reviewed patient clinical information to determine the course of treatment before they reviewed results from the molecular diagnostic classifier and subsequently evaluated whether the predicted diagnosis would alter their treatment plan. Results from the molecular diagnostic classifier changed the consensus oncologist-reported treatment recommendations for 235 out of 289 patients (81.3%). At the level of individual oncologist reviews (n = 414), 64.7% (n = 268) of treatment recommendations were based on CUP guidelines prior to review of results from the molecular diagnostic classifier. After seeing classifier results, 98.1% (n = 207) of the reviews, where treatment was specified (n = 211), were guided by the tissue of origin-specific guidelines. Overall, 89.9% of the 414 total reviews either expressed strong agreement (n = 242) or agreement (n = 130) that the molecular diagnostic classifier result increased confidence in selecting the most appropriate treatment regimen. A retrospective review of CUP cases demonstrates that a novel molecular diagnostic classifier could affect treatment in the majority of patients, supporting its clinical utility. Further studies are needed to prospectively evaluate whether the use of molecular diagnostic classifiers improves clinical outcomes in CUP patients.

Association of pretreatment chest CT abnormalities with trastuzumab deruxtecan–associated pneumonitis.

1106 Background: Trastuzumab deruxtecan (T-DXd) is an antibody-drug conjugate approved for HER2+ metastatic breast cancer (MBC) and HER2-low (IHC 1+ or 2+ with FISH-) MBC . Pneumonitis with T-DXd has been observed in 13.6% of patients (pts) on DESTINY-Breast 01 (including 2.2% fatal events) and 12.1% in pts on DESTINY-BREAST 04 (including 0.8% fatal events). There is an unmet need to determine if pts with baseline lung abnormalities are at increased risk for development of pneumonitis from T-DXd. Methods: This retrospective cohort study included all pts treated with T-DXd for MBC at an academic institution from 1/2020 to 2/2023 for more than 1 cycle (&gt;21 days). Outcomes were evaluated from treatment initiation until 2/1/2023. Two board-certified radiologists blinded to outcomes reviewed staging chest CTs performed before initiating T-DXd and graded each scan on 16 parenchymal abnormalities, including presence of interstitial lung abnormalities (ILA). Pneumonitis was retrospectively adjudicated by an independent oncologist using chart review and graded according to CTCAE v5.0 and compared to the treating physician’s assessment. The difference of proportions was analyzed with the Pearson Chi-Square test. Significance was declared at the 0.05 type I error threshold. Results: A total of 68 pts (median age 57.3 years) were included (30 = HER2+, 24 = HR+/HER2 low, 14 = TNBC/HER2 low). By independent assessment, 16 pts (23.5%) had grade 1 pneumonitis and 3 pts (4.4%) grade 2 pneumonitis. Median time from treatment initiation to pneumonitis was 83 days (range 35-266). By treating physician assessment, 5 pts (7.4%) developed grade 1 pneumonitis and 3 pts (4.4%) developed grade 2 pneumonitis. 16 of 68 pts (23.5%) had baseline ILA and 62 pts (91.2%) had at least one other parenchymal abnormality. As assessed by an independent oncologist, of pts with baseline ILA (N = 16), 12.5% developed T-DXd related pneumonitis, compared to 32.7% of pts without pre-existing ILA (N=52), p=0.16. There was no statistical difference in T-DXd related pneumonitis assessed by treating physician between pts with baseline ILA (2/16 patients, 12.5%) compared to pts without baseline ILA (7/52 pts, 13.5%), p=0.68. Conclusions: In this study, presence of baseline ILA was not associated with subsequent pneumonitis from T-DXd. Notably, the rate of independently assessed pneumonitis was higher than treatment-attributed pneumonitis as defined by the treating physician. Further research is needed to validate these findings and define predictors of treatment-associated pneumonitis. [Table: see text]

Prognostic impact of copy number alterations and tumor mutational burden in carcinoma of unknown primary.

Chromosomal aberrations are known to drive metastatic spread, but their profile is still elusive in carcinoma of unknown primary (CUP). Therefore, the aim of this study was to characterize the chromosomal aberration pattern in CUP depending on histological and clinical features and to assess its prognostic impact together with chromothripsis, tumor mutational burden (TMB), microsatellite instability (MSI), and mutational profiles as potential prognostic biomarkers. Chromosomal aberrations and chromothripsis were detected by methylation-based copy number variation (CNV) analysis, whereas TMB and MSI were calculated based on large next-generation sequencing (NGS) panels. Putative primaries were assigned by consensus between two independent oncologists. CNV losses varied depending on putative primaries and were more abundant in patients harboring TP53 mutations and/or deletions 17p. CNV loss was prognostically adverse in localized CUP treated with surgery and/or radiotherapy, but not in disseminated poor-risk CUP treated with palliative chemotherapy. CNV loss also worsened the prognosis in squamous cell CUP. Chromothripsis was detected in 18/59 (30.5%) patients without prognostic effect. TMB was highest in cases with MSI, squamous cell histology, and with lung, anal or cervical putative primaries. Overall, CNV, chromothripsis, TMB, and MSI profiles in CUP are reminiscent of biological characteristics known from other cancer entities without a unifying CUP-specific signature. Markedly, high-level CNV loss is an adverse predictive biomarker in localized but not disseminated chemotherapy-treated CUP. This implies that chromosomal losses drive CUP progression, but also increase susceptibility to chemotherapy, with both effects apparently leveling out in disseminated CUP.

Toxicities with combination BRAF and MEK inhibition in resected stage III melanoma.

e22086 Background: Patients with stage III melanoma are at high risk for recurrence after resection of the primary lesion. The Combi-AD study showed adjuvant therapy with BRAF inhibitor, dabrafenib (D), and MEK inhibitor, trametinib (T), in patients with resected stage III BRAF mutant melanoma offers recurrence free survival benefit at 3 and 4 years compared to placebo. In this study, adverse events led to dose interruption in 66% of patients, dose reduction in 38% of patients, and permanent discontinuation in 26% of patients. This is a retrospective case series of patients with resected stage III melanoma treated with adjuvant BRAF and MEK inhibition reporting toxicities in a real-world population. Methods: Medical records of all patients with resected Stage III melanoma treated with adjuvant D+T by multiple, independent oncologists at our institution between November 2017 and December 2019 were reviewed. Planned treatment was dabrafenib 150 mg bid and trametinib 2 mg daily for 1 year. Primary outcome of interest was development of toxicities. Secondary outcomes included number of treatment interruptions, dose reductions, and total time on combination therapy. Results: Twenty patients were treated with adjuvant D+T during the study period. Eighteen patients (90%) required at least 1 treatment interruption due to adverse events. Eleven patients (55%) required a dose reduction and 14 (70%) permanently discontinued therapy due to an adverse event. The 9 patients who did not require dose reduction had been initiated on a lower dose of dabrafenib (75 mg BID) due to physician experience with toxicities in prior patients. The most common treatment-limiting adverse events were recurrent pyrexia (85%) and liver laboratory abnormalities (50%). Permanent discontinuation was secondary to recurrent pyrexia in 9 patients (45%) and liver laboratory abnormalities in 5 patients (25%). For the 16 patients who completed or discontinued therapy, the median total time on therapy was 76 days, 20.8% of the intended duration. The majority of these patients never reached the FDA labeled combination dose. Conclusions: We report our findings of the side effects of adjuvant D+T to demonstrate the frequency and severity of treatment limiting toxicities in a real-world population, which exceeds what has been reported in clinical trials. Adjuvant D+T is an approved treatment for resected stage III melanoma but requires diligent toxicity assessment and management.

Response and Intervention to Elevated ESAS Scores: A Chart Audit of Gynecologic Oncology Clinics

While the incorporation of patient-reported outcomes (PROs) in oncology has several benefits, data pertaining to symptom management practices are limited. The objective of this study was to evaluate health care professional (HCP) documentation of elevated PRO symptom scores and subsequent intervention. This was a retrospective chart review of gynecologic oncology patients within a single institution. The Edmonton Symptom Assessment System (revised version) (ESAS-r) is a validated, PRO tool that evaluates 9 common symptoms and is completed prior to each clinic visit. Symptom management intervention guidelines exist for each symptom based on severity: mild (1-3), moderate (4-6) and severe (≥7). Biopsy-proven gynecologic oncology patients with any ESAS symptom score ≥4 were eligible. A stratified sampling method was used: 100 patients were randomly selected with 20 per year from 2012 to 2016. Patient, tumor and treatment characteristics were collected. HCP documentation of symptoms with score ≥4 and subsequent interventions were assessed by 2 independent oncologists. Interventions were categorized as: counselling, investigation, treatment or referral. Descriptive statistics were used to report symptom prevalence, HCP documented response and intervention. Fisher’s exact test evaluated documentation and intervention rates according to individual symptom severity and total ESAS score. Between January 2012 and December 2016, a total of 5849 patients completed the ESAS. Symptoms scores were ≥ 4 in 3216 patients (55%) and ≥ 7 in 1446 (25%). In our sample of 100, ovarian malignancies were most common (42%), followed by endometrial (34%). Median age was 55 years (range 47-63). The median total ESAS score was 24 (range: 17-39). The most prevalent symptoms were tiredness (70%), anxiety (61%) and poor appetite (40%). Overall, documentation of a least one symptom ≥ 4 occurred in 50 patients (50%), most commonly for pain (71%) and tiredness (36%) and least commonly for depression (11%) and nausea (4%). An intervention was offered to only 32 patients (32%), most commonly for pain (56%) and least commonly for nausea (4%). The primary intervention was a treatment recommendation (12/32; 38%). Higher median total ESAS score was associated with higher rate of documentation (p=0.002) and higher rate of intervention (p<0.001). Similarly, higher symptom severity was significantly associated with higher rate of documentation, except for anxiety and nausea, and higher rate of intervention, except for anxiety, nausea and tiredness. A significant proportion of gynecologic oncology patients report elevated symptom scores that should prompt an intervention. However, HCPs document symptoms in only half of patients and offer interventions in only one third, warranting further evaluation. A study exploring the barriers and facilitators of optimal ESAS use is underway.

Creating Virtual Integration and Improved Oncology Care Quality Through a Co-Management Services Agreement

Implementation of a co-management services agreement (Co-MSA) creates agreed-upon cancer care delivery quality metrics, a forum for discussion of service line oversight, and virtually integrated care without institutional employment of oncologists. The goal of this project was to demonstrate that a Co-MSA improved predefined quality metrics and provided enhanced communications between a health system's oncology service line and a group of independent oncologists. Iterative planning discussions were scheduled biweekly over an 18-month period. Contractual, quality, and clinical data with benchmarking were considered in the creation of the Co-MSA. Review of the first year's implementation occurred through examination of the metric achievements and qualitative themes that arose through committee meetings, clinical implementation processes, and cross-organizational discussions. Metrics designed for the Co-MSA included improved adherence to the breast cancer, colon cancer, and non-small-cell lung cancer level I pathways; improvement of the medical oncology physician communication component of the hospital system's Hospital Consumer Assessment of Healthcare Providers and Systems survey scores; and increased delivery of survivorship care plans to appropriate patients. Nonquantifiable themes from the first year of implementation included the need for technology to collect data, both organizations needing a wider understanding of quality improvement techniques, and a need for greater executive leadership involvement. In its first year, the Co-MSA resulted in improvement of the delivery of survivorship care plans and adherence to value pathways powered by the National Comprehensive Cancer Network. Improvement of Hospital Consumer Assessment of Healthcare Providers and Systems scores did not occur.

Transvaginal ultrasound (TVUS)-guided biopsy is safe and effective in diagnosing peritoneal carcinomatosis and recurrent pelvic malignancy

To assess safety and accuracy of transvaginal ultrasound (TVUS)-guided biopsy in achieving a diagnosis of peritoneal carcinomatosis (PC). This was a retrospective study comprising a cohort of 54 consecutive women aged 18-85 years referred from the gynaecological oncology multidisciplinary team meeting (MDTM) who attended for TVUS-guided biopsy procedures in a tertiary oncology centre over a 4-year period (2010-2014). Clinicopathological validation was assessed using online patient records and radiological information systems. An independent oncologist assessed patient outcomes. The procedure was successful in all 19 patients with suspected recurrent malignancy with diagnosis validated against previous histology. Successful histological confirmation was achieved in 31 of 35 patients with suspected PC, which was thereafter validated by histology from subsequent surgery and favourable response to site-specific therapies (n=22). In three patients with suspected PC, the procedure did not result in biopsy as a suitable target could not be identified. Another woman had two false-negative biopsies. Thus overall a site-specific and subtype cancer diagnosis was obtained for 50 women giving an overall patient success rate of 93% (50/54). There were no procedure-related complications. TVUS core biopsy is a safe, effective, well-tolerated, and valuable technique in modern oncological management of PC when other diagnostic options are unavailable.

Hematologic Malignancies: Impact of an Integrated Pathology Process and Decision Support Tool on Diagnosis and Follow-up Health Care Costs

Background: The process of integrating and interpreting information from multiple diagnostic tests, which may have been provided by multiple laboratories, can result in inaccurate diagnoses and treatment delays for patients with hematologic malignancies. A diagnostic process and decision support tool that integrates laboratory results and guides clinical diagnosis may improve diagnostic accuracy and targeted treatment. This study compares the completeness and actionability of bone marrow biopsy work-up results as well as follow-up health care costs for patients with suspected hematologic cancers whose diagnostic tests were managed by specialty hematology and other types of laboratories.Methods: Adult patients who had undergone a bone marrow biopsy (BMB) and had been diagnosed with a hematologic condition between January 2007 and March 2012 were identified from a large US commercial health insurance database affiliated with Optum. Patient cohorts were identified based upon laboratories performing marrow morphologic assessment/directing testing sequence: Genoptix (GX, a specialty hematology-testing laboratory) and large commercial laboratories and other laboratories such as community hospital laboratories (OL); academic labs were not included. Cohorts identified for medical chart review were matched for age, sex, geographic region, primary diagnosis on the bone marrow biopsy index date, comorbidity score, and all-cause health care costs. Medical charts were obtained from the BMB-referring physician. Independent oncologists and hematologists reviewed patients’ medical charts to determine the impact of BMB pathology reports on diagnosis and disease management. GX and OL reports were compared for completeness (diagnostic work-up in accordance with guidelines and no additional tests recommended) and actionability (enough information provided to make or rule out a diagnosis and to generate treatment recommendations). Administrative claims health care costs per patient per month (PPPM) for the period 30 days post-biopsy through 12 months were examined. Logistic regression assessed differences between cohorts for completeness, actionability and definitive diagnosis adjusted for age, gender, comorbidity and initial diagnosis on the index date. Generalized linear models assessed costs, adjusting for demographics, baseline clinical characteristics, initial diagnosis on the BMB date, definitive diagnosis, completeness and actionability on the BMB work-up report.Results: This analysis included 499 subjects with BMB results from GX (n=249) or OL (n=250). Overall, average age of patients was 52 (SD 12) with baseline Quan-Charlson score of 1.2 (SD 1.5). The majority of patients had a non-cancer hematological condition diagnosis on the index date (GX 64% and OL 56%) rather than a specific hematological cancer diagnosis. The GX BMB work-up reports were more likely to be complete (OR 2.2; p=0.001) and provide a definitive diagnosis (OR 2.1; p< 0.001) than the OL BMB work-up reports. The odds for GX reports to be actionable compared to OL reports for actionability were greater (OR 1.3) although not statistically significant. Follow-up PPPM overall health care costs for GX patients were 32% (p=0.04) lower than for the OL patients.Conclusions: Comprehensive integrated reports of complete bone marrow biopsy work-up results provide advantages over traditional lab reports by highlighting critical information and ensuring testing is completed according to both guidelines and clinical need. DisclosuresBrenneman:Optum: Employment. Belland:Optum: Employment. Hulbert:Optum: Employment. Korrer:Optum: Employment, Equity Ownership.

Exploratory analysis of nibrin in advanced ovarian cancer (AOC) patients treated in the phase III OVA-301 trial.

5566 Background: Nibrin (p95/NBS1) is a protein with an essential function in DNA double-strand break repair by homologous recombination. Therefore, we have investigated its value as a possible biomarker in patients with AOC by immunohistochemistry (IHC). Methods: IHC staining was performed in 138 samples from a subset of patients that have participated in the phase III OVA-301 trial, in which the combination of trabectedin plus pegylated liposomal doxorubicin (PLD) or PLD alone were randomly administered for advanced disease after failure of platinum-based chemotherapy (Monk 2010; Monk 2012). A computerized image analysis system was used to calculate the total percentage of nibrin-positive cells. Nibrin expression was considered as a continuous variable. The analysis of overall response rate (ORR) and progression-free survival (PFS) was based on independent oncologist assessment. Overall survival (OS) was defined from randomization to death/last contact. All the comparisons had an exploratory nature; an alpha cut-off value of 0.05 (two-sided) was established as statistically significant. Results: For PFS, there was a statistically significant correlation between high levels of nibrin and short PFS (HR = 1.014, 95% CI: 1.004-1.024, p=0.0047). Similarly, for OS, there was a statistically significant correlation between high levels of nibrin and worse OS (HR = 1.009, 95% CI: 1.001-1.017, p = 0.0295). A multivariate analysis showed that high levels of nibrin were independently correlated to a worse PFS (HR = 1.012, 95% CI: 1.002-1.022, p = 0.0147) and to a worse OS (HR = 1.010, 95% CI: 1.002-1.018, p=0.0192). After stratification according to platinum-sensitivity, high nibrin showed a significant correlation with lower ORR (ORR = 1.02, 95% CI: 1.01-1.03, p=0.0009), short PFS and OS values only in the platinum-sensitive patients. Conclusions: The results point out the potential importance of nibrin expression in the clinical outcome of patients with AOC. In particular, high protein expression of nibrin seems to be associated with a worse clinical outcome. Prospective clinical trials evaluating the clinical usefulness of this marker with other standard of care treatments are warranted. Clinical trial information: NCT00113607.

984P - Conservative Sensitivity Analyses of Progression-Free Survival (PFS) of Trabectedin Plus Pegylated Liposomal Doxorubicin (PLD) Vs. Pld Alone in Patients with Relapsed Ovarian Cancer: Ova-301 Study

ABSTRACT Background Sensitivity analyses are critical to understanding the strength of conclusions made in the primary analysis. A randomised phase III trial OVA-301 compared the efficacy of trabectedin 1.1 mg/m2 in combination with PLD 30 mg/m2 given every 3 weeks vs. PLD 50 mg/m2 every 4 weeks in patients with relapsed ovarian cancer. Primary endpoint was PFS based on independent radiology review (IRR) per RECIST. Secondary PFS analyses were based on independent oncologist (IO) and investigator's assessments (IA). Methods Patients were assessed symmetrically every 8 weeks in both arms. To avoid bias of the disease assessment time, two conservative sensitivity analyses of PFS were performed. Two different conservative analyses considered the scheduled date of PFS evaluation instead of the actual date of imaging moving the actual date to: #1) the last scheduled date of assessment immediately before the actual evaluation and to #2) the closest scheduled date before or after the actual evaluation. Results The treatment effect based on the actual dates of assessment in favour of the combination arm is maintained across the performed sensitivity analyses. Summary of the two sensitivity PFS analyses compared with the pre-planned PFS analysis. Analysis n Trabectedin + PLD PLD HR CI 95% LR test (p value) PFS by IR * 645 328 317 0.789 0.646-0.963 0.0190 PFS by IR ( #1 ) 645 328 317 0.813 0.666-0.993 0.0245 PFS by IR ( #2 ) 645 328 317 0.822 0.674-1.004 0.0317 PFS by IO * 671 336 335 0.724 0.599-0.876 0.0008 PFS by IO ( #1 ) 671 336 335 0.749 0.620-0.906 0.0010 PFS by IO ( #2 ) 671 336 335 0.757 0.626-0.916 0.0013 PFS by IA * 672 337 335 0.723 0.608-0.859 0.0002 PFS by IA ( #1 ) 672 337 335 0.742 0.624-0.882 0.0001 PFS by IA ( #2 ) 672 337 335 0.747 0.629-0.888 0.0001 CI, confidence interval; HR, hazard ratio; IA, investigator assessment; IO, independent oncology review; IR, independent radiology review; LR, log-rank; PFS, progression-free survival; PLD, pegylated liposomal doxorubicin. * *Main PFS analyses. #1 #1: Conservative PFS sensitivity analysis; imputation to the previous schedule evaluation. #2 #2: Sensitivity analysis with imputation to the closest scheduled evaluation. Conclusions The consistently observed significantly better PFS for the trabectedin combination based on adjusting progression times by moving assessments to scheduled times added methodological strengths and increased reliability and interpretability of the prior findings of this phase III trial. Disclosure A. Tanovic: I am an employee at PharmaMar and stock owner. J. Gomez Garcia: I am an employee at PharmaMar and stock owner. A.M. Poveda: I received funding for research from PharmaMar. All other authors have declared no conflicts of interest.

A new informed consent form model for cancer patients: Preliminary results of a prospective study by the Italian Association of Medical Oncology (AIOM)

ObjectivesTo document the preliminary validity of a new informed consent form (ICF) model in terms of face/content validity and feasibility, to collect patients’ and oncologists’ opinions on it, and to explore physicians’ and patients’ “knowledge”, “opinions” about “the information exchanged”. MethodsThe working group for informed consent promoted by the Italian Association of Medical Oncology developed a new ICF model which was tested in ten Italian cancer centers. Patients and physicians received questionnaires on the new ICF model. Twenty-six independent oncologists were interviewed to collect their opinions. ResultsSeventy eight cancer patients were enrolled: about 90% reported having received information about diagnosis and therapy and 80% about prognosis. About 63% of oncologists had no difficulty in administering the ICF. Oncologists used “correct terms” about diagnosis in 92% of patients with localized disease and in 90% with metastasis and about therapy in respectively 75.7% and 80%. About prognosis, oncologists used “vague” and “no information–no pertinent terms” in 79% of patients with localized disease and 92.5% of patients with metastasis. ConclusionsThe ICF seemed to have sufficient validity and feasibility. Practice implicationThis ICF model could mean that patients require oncologists to spend more time explaining the diagnosis, prognosis and treatment, increasing patient's opportunities to participate actively in the care process

Detection of Cancer by Optical Analysis of Body Fluids — A Single Blind Study

This paper pertains to a new technique based on fluorescence emission spectra (FES), and stokes shift spectra (SSS) of blood plasma, acetone extract of cellular fraction, and urine. These samples were collected from 60 cancer patients of different etiology and 60 age adjusted controls for a single blind study. A set of ratio parameters were obtained from the above spectra (FES and SSS of above three sets of samples), based on the relative intensity of biofluorophores like tryptophan, tyrosine, flavin etc. It was found that these biofluorophores go out of proportion for malignancy of any etiolology. The study was done in two phases: calibration and validation. Based on a certain set of ratios obtained by simple statistical analysis, in the calibration phase, the blinded samples of validation phase were spectrally analysed and classified as normal or malignant. The scoring done by independent oncologists (who were not involved in any part of this new technique) yielded an overall sensitivity of 87%, and specificity of 83%. The result indicate that new optical spectroscopic techniques could be a simple, non-invasive protocol for detection of cancers, particularly in symptomatic cases; or for monitoring the post treated cases of cancer.

Abstract P6-05-02: Clinical-Pathological Features of All Nodules with the Same Histotype Affect Systemic Adjuvant Treatment Decision in Multifocal and Multicentric Breast Cancer

Abstract BACKGROUND Decision criteria about systemic adjuvant treatment of patients affected by breast cancer include estrogen receptor (ER), progesterone receptor (PgR), HER2 status, histologic grading, and proliferative index. In case of multifocal or multicentric breast cancer, the College of American Pathologists (CAP) recommends to provide features for the largest invasive carcinoma. We evaluated the discordance of ER, PgR, HER2, grading, and proliferative index among all nodules with the same histotype of patients with multifocal or multicentric breast cancer and the impact on the choice of adjuvant treatment. METHODS We retrospectively analyzed 113 consecutive patients operated for breast cancer between 2004 and 2009 in Forli (Italy). We performed histological examination of all nodules of each patient after surgery, at the same time. Immunohistochemical methods were used to detect ER/PgR status, and proliferative index (Ki67), whereas fluorescent in situ hybridization was used to determine HER2 status. ER/PgR &amp;lt; 10% was considered negative. Ki67 was considered high if ≥20%. Grading was determined according to Nottingham's score system. HER2 amplification was defined according to CAP guidelines or as the presence of a focal HER2 amplified clone ≥30% of tumor cells. We considered as “discordance” a difference in at least one nodule for any of the biologic features considered. In order to determine whether discordance among nodules affects systemic treatment approaches, we asked ten independent oncologists whether and how they would modify their prescribed adjuvant treatment. RESULTS Discordance in ER or PgR status among different nodules was detected in 5 (4.4%) and 16 patients (14.1%), respectively. The majority of the oncologists (7 out of 10) decided to modify their prescribed systemic treatment in 3 patients (2.6%), in favor of a combined treatment (endocrine plus chemotherapy), instead of endocrine-or chemotherapy alone as if their decision was based on the receptor status only of the largest nodule. Discordance in HER2 status was detected in 10 (8.8%) patients. In 4 patients (3.5%), all clinicians found indication to an anti-HER2 treatment. Discordance in proliferative index occurred in 17 (15.0%) patients and discordance in grading was detected in 18 (17.8% over 101) patients. Five of ten oncologists decided to modify their prescribed systemic treatment by adding chemotherapy to endocrine-therapy alone in 5 patients (4.4%) based on Ki67 value, whereas there was no change based on grade. DISCUSSION This study shows a discordance for all analyzed histological features among different nodules with the same histotype in multifocal and multicentric tumors. In a total of 8 patients (about 7%) this discordance affected the therapeutic decisions of oncologists, resulting in changes of the prescribed adjuvant systemic treatment, with respect to the prescriptions based on the clinicopathologic features only of the largest nodule. Therefore, we conclude that the analysis of all nodules in case of multifocality/multicentricity should be taken into consideration, in order to identify the best adjuvant treatment. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-05-02.

Independent Adjudication of Symptomatic Heart Failure With the Use of Doxorubicin and Cyclophosphamide Followed by Trastuzumab Adjuvant Therapy: A Combined Review of Cardiac Data From the National Surgical Adjuvant Breast and Bowel Project B-31 and the North Central Cancer Treatment Group N9831 Clinical Trials

An independent Adjuvant Cardiac Review and Evaluation Committee (ACREC) systematically reviewed cases of symptomatic heart failure events to uniformly define the cardiac event rate across two large trials (National Surgical Adjuvant Breast and Bowel Project [NSABP] B-31 and North Central Cancer Treatment Group [NCCTG] N9831) that assessed the addition of trastuzumab to standard adjuvant chemotherapy. The committee was composed of six independent oncologists and cardiologists. A retrospective review of patients with a cardiac event was performed by the primary investigators of the trials. The ACREC prospectively established criteria for determining a symptomatic heart failure event. Recovery status was determined from documented resolution of signs and symptoms. Potential risk factors were also assessed. Medical records for a total of 173 patients were reviewed: 40 in the chemotherapy-alone arm and 133 in the trastuzumab arm. Trastuzumab-treated patients had a 2.0% incidence of symptomatic heart failure events compared with 0.45% in the chemotherapy-alone arm. Complete or partial recovery was observed in 86.1% of trastuzumab-treated patients with symptomatic heart failure events. Of five patients who died, only one patient had received trastuzumab. Independent predictors for cardiac events were age older than 50 years, a low ejection fraction at the start of paclitaxel treatment, and trastuzumab treatment. The incidence of symptomatic heart failure events is 2.0% in patients treated with adjuvant trastuzumab, and the majority of these patients recover with appropriate treatment.

Clinical Co-Management: Hospitals and Oncologists Working Together.

The Centers for Medicare & Medicaid Services (CMS) and almost every major health care trade organization or third-party payer have launched a focused quality initiative of some type. Physicians and hospitals prepared to prove their superior quality will have a leading role in establishing relevant benchmarks and metrics for quality performance. Reactive providers will be judged simply by the established standards. Defining quality care, beyond the quality-award-of-the-week approach, will likely require tighter integration of physician practice and hospital infrastructure. Here, I outline a new legal construct for this integration. Clinical co-management is an important new model for the integration of physician and hospital management of clinical services. In this arrangement, physicians provide medical management services with a hospital at a level substantially beyond conventional medical director agreements. Clinical co-management arrangements are typically structured between an organized group of oncologists (or other physicians) and a health care system. The oncologists are engaged to assist the health care system in the management of certain elements of its inpatient and outpatient service line to make the service line more competitive in a targeted market. A critical feature is the existence of a written agreement, which governs the relationship. Clinical co-management arrangements directly involve oncologists as participants in the day-to-day management of the hospital's clinical operations. One of the positive attributes of the clinical co-management model is the substantial clinical and operational input the physicians typically have. Such input helps align the physician and hospital interests and achieve quality in patient care. For example, the agreement with the hospital typically requires direct physician participation in the design and oversight of annual clinical capital and operating budgets, the development and implementation of clinical strategies and business plans, the efficient delivery of physician and clinical staff services, the periodic assessment of the quality of patient care delivered, the measurement of patient satisfaction, and the development of clinical outreach programs. Clinical co-management arrangements may be designed with a specific quality emphasis. In the clinical quality improvement setting, the physicians provide leadership and clinical consulting services designed to develop quality performance improvement plans and to help implement and execute those plans. For example, clinical co-management arrangements may be used to create durable alliances between groups of independent oncologists and acute care hospitals. In a more integrated setting, a quality incentive pool may be used to fund a nonqualified deferred compensation program for participating physicians. Where nursing recruiting and retention are key priorities, a quality-based retention incentive may be used to reward nursing units for improving patients' clinical outcomes while achieving high marks for patient satisfaction. A clinical co-management arrangement typically divides physician compensation into two categories: hourly compensation for clinical program supervision; and a performance bonus based on approved objectives including clinical quality, clinical outcomes, patient satisfaction, referral-doctor satisfaction, and measurable improvement in operating efficiencies. Compensation is also subject to a predetermined annual cap. Additionally, clinical co-management arrangements can be constructed in conjunction with gain-sharing activities. For more information, see the November 2005 Legal Corner, “Can Hospitals Share Cost Savings With Their Oncologists?” (J Oncol Pract 1:152, 2005).

Radiation treatment planning with an integrated positron emission and computer tomography (PET/CT): a feasibility study

Purpose To investigate the usefulness of hardware coregistered PET/CT images for target volume definition. Methods and materials Thirty-nine patients presenting with various solid tumors were investigated. CT and a FDG-PET were obtained in treatment position in an integrated PET/CT scanner, and coregistered images were used for treatment planning. First, volume delineation was performed on the CT data. In a second step, the corresponding PET data were used as an overlay to the CT data to define the target volume. Delineation was done independently by two investigators. Results Coregistered PET/CT showed good fusion accuracy. The GTV increased by 25% or more because of PET in 17% of cases with head-and-neck (2/12) and lung cancer (1/6), and in 33% (7/21) in cancer of the pelvis. The GTV was reduced ≥25% in 33% of patients with head-and-neck cancer (4/12), in 67% with lung cancer (4/6), and 19% with cancer of the pelvis (4/21). Overall, in 56% (22/39) of cases, GTV delineation was changed significantly if information from metabolic imaging was used in the planning process. The modification of the GTV translated into altered PTV changes exceeding >20% in 46% (18/39) of cases. With PET, volume delineation variability between two independent oncologists decreased from a mean volume difference of 25.7 cm 3 to 9.2 cm 3 associated with a reduction of the standard deviation from 38.3 cm 3 to 13.3 cm 3 ( p = 0.02). In 16% of cases, PET/CT revealed distant metastasies, changing the treatment strategy from curative to palliative. Conclusion Integrated PET/CT for treatment planning for three-dimensional conformal radiation therapy improves the standardization of volume delineation compared with that of CT alone. PET/CT has the potential for reducing the risk for geographic misses, to minimize the dose of ionizing radiation applied to non-target organs, and to change the current practice to three-dimensional conformal radiation therapy planning by taking into account the metabolic and biologic features of cancer. The impact on treatment outcome remains to be demonstrated.