Degree Of Cytoreduction Research Articles

The right time for change: A report on the heterogeneity of IVB endometrial cancer and improved risk-stratification provided by new 2023 FIGO staging criteria

ObjectiveWe sought to provide a contemporary report on stage IVB endometrial carcinoma (2009 FIGO criteria) and applied the 2023 FIGO staging criteria to this population. MethodsRetrospective review of patients who underwent cytoreduction for stage IVB endometrial carcinoma (2009 FIGO criteria) from 2014 to 2020 was performed. Demographics, clinicopathologic factors, and outcomes were recorded. Disease burden and distribution were determined by imaging, operative notes, and pathology reports. Patients were re-staged according to 2023 FIGO staging criteria. Categorical variables were compared using χ2 or Fisher's exact test, and Kaplan-Meier curves compared survival outcomes using the log-rank test. ResultsEighty-eight cases were included. Most patients (63.6%) were not suspected to have stage IVB (2009 FIGO criteria) disease prior to surgery. Seventy-two percent of patients underwent primary cytoreduction, and 12 (19%) were suboptimal. Median progression-free survival (PFS) was 12 months (95% CI 10–16 months), and median overall survival (OS) was 38 months (95% CI 19–61 months). Degree of cytoreduction (p = 0.0101) and pelvic-confined metastatic disease (p = 0.0149) were significant prognostic factors, while distant metastases were not associated with worse outcomes. For those patients who underwent primary cytoreduction, number (p = 0.0453) and diameter (p = 0.0192) of tumor deposits were associated with PFS. When 2023 FIGO staging criteria were applied, 58% of patients underwent change in stage, and 8% did not meet criteria for complete staging. PFS was significantly different based on 2023 FIGO staging (p = 0.0307); a trend in OS was also noted (p = 0.0550). ConclusionStage IVB endometrial carcinoma (2009 FIGO criteria) encompasses a diverse cohort of patients, where certain clinicopathologic features, tumor burden, and degree of cytoreduction are associated with outcomes. The 2023 FIGO staging criteria significantly improves our ability to risk-stratify patients.

CT Enterography for Preoperative Evaluation of Peritoneal Carcinomatosis Index in Advanced Ovarian Cancer.

To compare the diagnostic performance of routine CT (rCT), CT enterography (CTE) and intraoperative quantification of PCI to surgical and pathological reference standards in patients with advanced ovarian cancer, a retrospective study of 122 patients who underwent cytoreduction surgery for ovarian peritoneal carcinomatosis was conducted. Radiological, surgical, and pathological PCIs were obtained from the corresponding reports, and the latter two were considered reference standards. The radiological techniques used were rCT: 64 MDCT (32 × 1 mm) (100 mL iopromide 370 i.v., 800 mL water p.o.), and CTE: 64 MDCT (64 × 0.5 mm) (130 mL iopromide 370 i.v., 1800 mL mannitol solution p.o., 20 mg buscopan i.v.). Data were grouped by imaging technique and analyzed using total PCI and stratified by tumor burden (low-PCI < 10, high-PCI > 20). Agreement, diagnostic performance and degree of cytoreduction were evaluated. Disappointing results for rCT and CTE were obtained when using a surgical referent, but better diagnostic performance and concordance (0.86 vs. 0.78 vs. 0.62, p < 0.05) was observed when using a pathological referent—surgical PCI overestimates and overstaged patients. PCI is underestimated by rCT rather than CTE. For high-PCI, the ROC curve was mediocre for CTE and useless for rCT, as it failed to identify any cases. For low-PCI, the ROC was excellent (86% CTE vs. 75% rCT). In four cases with low-PCI as determined by rCT, cytoreduction was suboptimal. CTE has a better diagnostic performance than rCT in quantifying PCI in patients with advanced ovarian cancer, suggesting that CTE should be used as the initial technique. Surgical-PCI could be considered as an imperfect standard reference.

Multispectral label-free Raman spectroscopy can detect ovarian and endometrial cancer with high accuracy.

Up to 70% of ovarian cancer patients are diagnosed with advanced-stage disease and the degree of cytoreduction is an important survival prognostic factor. The aim of this study was to evaluate if Raman spectroscopy could detect cancer from different organs within the abdominopelvic region, including the ovaries. A Raman spectroscopy probe was used to interrogate specimens from a cohort of nine patients undergoing cytoreductive surgery, including four ovarian cancer patients and three patients with endometrial cancer. A feature-selection algorithm was developed to determine which spectral bands contributed to cancer detection and a machine-learning model was trained. The model could detect cancer using only eight spectral bands. The receiver-operating-characteristic curve had an area-under-the-curve of 0.96, corresponding to an accuracy, a sensitivity and a specificity of 90%, 93% and 88%, respectively. These results provide evidence multispectral Raman spectroscopy could be developed to detect ovarian cancer intraoperatively.

Prognostic SIGNIFICANCE of Cytoreductive Therapy of Ovarian Cancer - eastern Croatia experience.

SUMMARYThe aim of this retrospective study was to present the impact of successful optimal cytoreductive therapy on the overall prognosis of ovarian cancer treatment. Several factors were analyzed, including clinical (stage, age and parity), histopathologic/cytological (histologic type and grade of tumors, cytological findings of ascites or peritoneal washout), and therapeutic (surgery performed with the degree of cytoreduction, adjuvant chemotherapy and response to therapy). The study included 126 patients treated during a 5-year period at the Department of Gynecology and Obstetrics, Osijek University Hospital Centre in Osijek. Patient age ranged from 29 to 82, total 5-year survival was 55.5% and median survival was 76.2 months. Optimal cytoreduction (residual tumor <1 cm) was performed in 49.2% of patients. On data analysis, the life chart method, χ2-test and Cox regression analysis were used. The level of significance was set at p<0.05. Parity, histologic tumor grade, presence of malignant cells in ascites and peritoneal washout, as well as clinical stage yielded statistical significance on univariate analysis. Cytoreductive ovarian cancer therapy turned out to be a significant prognostic factor and on multivariate analysis proven to be an independent prognostic factor. Optimal cytoreduction, besides direct effect on survival, improved the quality of therapeutic response of the tumor to chemotherapy.

High-Grade Serous Ovarian Cancer: Use of Machine Learning to Predict Abdominopelvic Recurrence on CT on the Basis of Serial Cancer Antigen 125 Levels

PurposeThe aim of this study was to use machine learning to predict abdominal recurrence on CT on the basis of serial cancer antigen 125 (CA125) levels in patients with advanced high-grade serous ovarian cancer on surveillance. MethodsThis institutional review board–approved, HIPAA-compliant, retrospective, hypothesis-generating study included all 57 patients (mean age, 61 ± 11.2 years) with advanced high-grade serous ovarian cancer who underwent cytoreductive surgery from January to December 2012, followed by surveillance abdominopelvic CT and corresponding CA125 levels. A blinded radiologist reviewed abdominopelvic CT studies until recurrence was noted. Four measures of CA125 were assessed: actual CA125 levels at the time of CT, absolute change since prior CT, relative change since prior CT, and rate of change since prior CT. Using machine learning, support vector machine models were optimized and evaluated using 10-fold cross-validation to determine the CA125 measure most predictive of abdominal recurrence. The association of the most accurate CA125 measure was further analyzed using Cox proportional-hazards model along with age, tumor size, stage, and degree of cytoreduction. ResultsRate of change in CA125 was most predictive of abdominal recurrence in a linear kernel support vector machine model and was significantly higher preceding CT studies showing abdominal recurrence (median 13.2 versus 0.6 units/month; P = .007). On multivariate analysis, a higher rate of CA125 increase was significantly associated with recurrence (hazard ratio, 1.02 per 10 units change; 95% confidence interval, 1.0006-1.04; P = .04). ConclusionA higher rate of CA125 increase is associated with abdominal recurrence. The rate of increase of CA125 may help in the selection of patients who are most likely to benefit from abdominopelvic CT in surveillance of ovarian cancer.

CYTOREDUCTIVE SURGERY WITH PERITONECTOMY IN PATIENTS WITH OVARIAN CANCER: TECHNICAL ASPECTS AND IMMEDIATE RESULTS

Results of numerous retrospective studies have confirmed that the degree of cytoreduction and the size of the residual tumor after the primary surgery are the most important factors affecting overall life expectancy as well as the time to progression in patients with ovarian cancer (OC). The article presents the immediate results of the first 16 extensive cytoreductive surgeries in advanced OC performed at the Oncogynecology Department of the N.N. Petrov National Medical Research Center of Oncology.

The impact of time and team on primary cytoreduction outcomes

The degree of cytoreduction at time of initial surgery for epithelial ovarian cancers is correlated with overall survival. Given that surgery can be physically and mentally taxing on the surgeon, we sought to examine if there were temporal and/or team relationships related to primary cytoreduction outcomes.

Timing and duration of primary debulking surgery on degree of cytoreduction

Timing and duration of primary debulking surgery on degree of cytoreduction

Optimal Outcomes in Young Class 3 Patients With Thalassemia Undergoing HLA-Identical Sibling Bone Marrow Transplantation.

Bone marrow transplantation (BMT) for class 3 patients with thalassemia is challenging due to high rates of graft rejection and transplant-related mortality. Since the first studies of BMT in the late 1980s, a number of conditioning regimens have been designed to improve outcomes, but with suboptimal results. Here we report the outcome of transplantation in class 3 patients using a modified protocol. Sixty-three patients between 5 and 16.7 years of age with class 3 thalassemia received HLA-matched sibling BMT following either the original protocol (26 patients) or the modified protocol (37 patients). Both regimens comprised preconditioning cytoreduction with hydroxyurea and azathioprine starting at -45 days pretransplant, and fludarabine from days -16 to -12. Conditioning was performed with busulfan and cyclophosphamide (original protocol) or with busulfan, thiotepa, and cyclophosphamide (modified protocol). The 2 groups showed similar patient demographics. At day 0, the degree of cytoreduction (lymphopenia, neuthropenia, and thrombocytopenia) achieved by the modified protocol was greater than the original protocol. The incidence of graft failure/rejection was significantly higher in the original group (15%; 95% confidence interval [95% CI], 5-32%) compared with the modified group (0%) (P = 0.014). The respective 5-year thalassemia-free survival rates were 73% (95% CI, 51-86%) and 92% (95% CI, 77-97%) (P = 0.047). Both groups showed similar incidences of grades II to IV acute graft-versus host disease. Modified protocol did not increase nonhematological toxicity or infectious complications. The modified treatment protocol effectively and safely prevented graft failure/rejection and significantly increased thalassemia-free survival of class 3 patients with thalassemia.

Do preoperative serum vascular endothelial growth factor and migration-inhibitory factor predict the nature of the adnexal masses? A prospective-controlled trial

The aim of this study was to identify the role of preoperative serum vascular endothelial growth factor (VEGF) and migration inhibitor factor (MIF) in differentiation of benign and malignant adnexal masses, as well as the relationship between prognostic factors and VEGF and MIF in ovarian cancer patients. This prospective study included 41 patients who were admitted between November 2010 and March 2012. In the malignant group, there were 21 patients, and remaining 20 had benign adnexal masses. Age, CA125 levels, grade, stage, presence of ascites and the degree of cytoreduction performed were noted. There was no significant difference between two groups in preoperative serum VEGF and MIF levels (p = 0.118 and p = 0.297, respectively). CA125 levels were significantly higher in the malignant group (p < 0.0001). There was no significant difference for VEGF and MIF between the groups evaluated for tumour grade, stage, presence of ascites and degree of cytoreduction performed in the malignant group. Preoperative serum, VEGF and MIF levels are not suitable for the differentiation of malignant and benign adnexal masses, and they do not correlate with the prognostic factors of ovarian cancer in this cohort of patients.

Transplant Outcomes in High-Risk (Class 3) Patients with Thalassemia Treated with a Modified Protocol Are Equivalent to Low/Intermediate-Risk (Class 1/Class 2) Patients

Introduction. Bone marrow transplantation (BMT) for class 3 patients with thalassemia is challenging due to high rates of graft rejection and transplant-related mortality. Since the first studies of BMT in the late 1980s, a number of conditioning regimens have been designed to improve outcomes, but with suboptimal results. Here we report the outcome of transplantation in class 3 patients using a modified protocol.Methods. Between July 2004 and May 2015, 68 consecutive patients of 5-16.6 years of age with class 3 thalassemia received their first BMT from HLA-identical sibling donors. Of these patients, 26 were prepared for transplantation with the original protocol (Protocol 26) and 42 patients (since February 2007) with the modified protocol. The original protocol started with a preconditioning phase during which patients received hydroxyurea (30 mg/kg/day) and azathioprine (3 mg/kg/day) from day −45 pre-transplant, and fludarabine (20 mg/m2/day) from day −16 through day −12. Conditioning regimen included oral or intravenous (i.v.) busulfan and cyclophosphamide 160 mg/kg total dose. The modified protocol started with the same preconditioning phase except with 30 mg/m2/day of fludarabine. The conditioning regimen comprised i.v. Bu, thiotepa 10 mg/kg/day, and cyclophosphamide 160 mg/kg total dose. We compared the outcomes between these two groups.The two groups showed similar patient demographics. Patients in both groups had moderately severe iron overload, as evidenced by high median serum ferritin and liver iron concentrations. The median liver fibrosis score in the original and modified protocol-treated patients was 2 (range, 1-4) and 1 (range 1-5) (p=0.22), respectively.Results. At day 0, the degree of cytoreduction (lymphopenia, neuthropenia and thrombocytopenia) achieved by the modified protocol was significantly higher than the original protocol. Overall, 22 (84.6%) original protocol-treated patients and all 42 modified protocol-treated patients showed sustained engraftment. Platelet and neutrophil engraftment kinetics were similar between groups. All patients with sustained engraftment achieved RBC transfusion independence, with a median time to transfusion independence of 19 days (range, 0-88) with original protocol and 20 days (range, 0-85) with modified protocol. Among original protocol-treated patients, two experienced primary graft failure and two experienced secondary graft failure. No modified protocol-treated patients exhibited graft failure. Competing-risk analysis showed a significantly higher cumulative incidence of graft failure with original protocol (15%) compared to modified protocol (0%) (p=0.010). At the time of survival analysis, 22 original protocol -treated patients (85%) and 39 modified protocol-treated patients (93%) were alive, with median follow-up durations of 8.8 years (range, 8.2-10.8 years) and 3.5 years (range, 0.4-8 years), respectively. The 5-year probabilities of thalassemia-free survival were 93% with modified protocol and 73% with original protocol (p=0.032). The respective probabilities of overall survival were 93% and 85% (p=0.37). The incidence of grade 2-4 acute GVHD was 46% in the original and 24% in the modified group (p=0.066). Respective incidences of chronic GVHD were 12% and 5%. At present all patients are off immunosuppressive medication. There were 4 deaths in the original group and 3 deaths in the modified group. The most frequently observed toxicities were grade 2 elevations in AST and ALT, followed by grade 2 oral mucositis and diarrhea with similar rates in both groups. Few patients experienced grade 3 liver and gut toxicities in either groups with similar rates. There was no difference in the rate of infectious complications between the two groups. One patient in each group developed moderate hepatic VOD, both of which resolved with supportive careConclusions. Modified treatment protocol effectively and safely prevented graft failure/rejection and significantly improved thalassemia-free survival of class 3 patients. Importantly, the treatment intensification was not associated with increased nonhematological toxicity, even though these patients suffer from pre-existing organ damage due to iron overload and/or hepatitis. Modified protocol makes allogeneic BMT accessible to all class 3 younger patients with results equal to class 1 or class 2 patients with thalassemia. DisclosuresNo relevant conflicts of interest to declare.

The optimal organization of gynecologic oncology services: a systematic review.

A system-level organizational guideline for gynecologic oncology was identified by a provincial cancer agency as a key priority based on input from stakeholders, data showing more limited availability of multidisciplinary or specialist care in lower-volume than in higher-volume hospitals in the relevant jurisdiction, and variable rates of staging for ovarian and endometrial cancer patients. A systematic review assessed the relationship of the organization of gynecologic oncology services with patient survival and surgical outcomes. The electronic databases medline and embase (ovid: 1996 through 9 January 2015) were searched using terms related to gynecologic malignancies combined with organization of services, patterns of care, and various facility and physician characteristics. Outcomes of interest included overall or disease-specific survival, short-term survival, adequate staging, and degree of cytoreduction or optimal cytoreduction (or both) for ovarian cancer patients by hospital or physician type, and rate of discrepancy in initial diagnoses and intraoperative consultation between non-specialist pathologists and gyne-oncology-specialist pathologists. One systematic review and sixteen additional primary studies met the inclusion criteria. The evidence base as a whole was judged to be of lower quality; however, a trend toward improved outcomes with centralization of gynecologic oncology was found, particularly with respect to the gynecologic oncology care of patients with advanced-stage ovarian cancer. Improvements in outcomes with centralization of gynecologic oncology services can be attributed to a number of factors, including access to specialist care and multidisciplinary team management. Findings of this systematic review should be used with caution because of the limitations of the evidence base; however, an expert consensus process made it possible to create recommendations for implementation.

Cytoreductive surgery and intraperitoneal hyperthermic chemotherapy in the treatment of peritoneal carcinomatosis

Cytoreductive surgery (CS) and intraperitoneal hyperthermic chemotherapy (IPHC) in the treatment of peritoneal carcinomatosis (PC) in 15 patients are described. Fifteen patients with PC who were treated with CS and IPHC were retrospectively identified between January 2002 and December 2006. All patients underwent cytoreduction immediately followed by IPHC with mitomycin or cisplatin. The time between undergoing CS and IPHC and the date of the last follow-up appointment or the date of death was used to calculate survival data for each patient. Nine patients had complete cytoreduction, and all but one patient had evidence of invasive disease at the time of surgery. Eleven patients required concomitant bowel resection at the time of debulking. Thirteen patients required blood transfusions during the perioperative period. Nine patients were discharged home, and four were discharged to a rehabilitation facility. Two patients died during the perioperative hospital admission, both of whom had a preoperative Eastern Cooperative Oncology Group (ECOG) performance status score of 2. The median survival time was 8.4 months, similar to the findings of previously published studies. Further studies are needed to see if tumor type, ECOG performance status score, degree of cytoreduction, and the chemotherapy agent used in IPHC can be correlated to quality of life and survival in patients with heterogeneous primary sources of intraabdominal malignancies. Combination treatment with CS followed by IPHC in 15 patients with heterogeneous primary sources of intraabdominal malignancies resulted in a median survival time of 8.4 months.

Aggressive Surgical Management of Peritoneal Carcinomatosis With Low Mortality in a High-Volume Tertiary Cancer Center

Cytoreductive surgery (CS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) for treatment of peritoneal carcinomatosis (PC) traditionally involves high perioperative morbidity and mortality. We report our experience performing CS-HIPEC in a high-volume regional perfusion program designed to limit morbidity and mortality. A total of 122 patients underwent 124 CS-HIPEC procedures. Common tumors treated with CS-HIPEC included appendiceal (38.5%), colorectal (24.6%), and ovarian cancers (13.1%), and peritoneal mesothelioma (12.3%). Complete cytoreduction was performed in all patients, with organ resections performed as necessary. R0 resection was achieved in 28.7% of cases, R1 in 54.9%, and R2 in 16.4%. Median operative time was 460 minutes (range, 250-840 minutes), and median blood loss was 1150 mL (range, 10-14,000 mL). Median hospital and intensive care unit stays were 12 days (range, 6-50 days) and 3 days (range, 0-41 days), respectively. Grade 3 or 4 morbidity by National Cancer Institute criteria (major morbidity) was seen in 29.8% of cases, with overall morbidity 56.5%. Independent prognostic variables for major morbidity included number of anastomoses and degree of cytoreduction. In-hospital and 30-day mortality rates were 0% and 1.6%, respectively. The most favorable diagnosis was appendiceal cancer, for which 2-year survival was 66.7%, with lower-grade histologic subtypes of appendiceal cancer reaching 85.7% 2-year survival. Colorectal cancer had 2-year survival of 36.7%. In a high-volume center with extensive experience treating peritoneal malignancies, perioperative mortality can be lowered to nearly zero, although morbidity remains high. CS-HIPEC procedures should be studied further in a controlled manner to help define their important role in the care of patients with PC.

A contemporary analysis of the ability of preoperative serum CA-125 to predict primary cytoreductive outcome in patients with advanced ovarian, tubal, and peritoneal carcinoma

5572 Background: We previously reported that preoperative CA-125 may predict primary cytoreductive outcome in patients (pts) with stage III ovarian carcinoma. We performed a contemporary analysis of the ability of preop CA-125 to predict cytoreductive outcome in advanced ovarian, tubal and peritoneal carcinoma. Methods: In 1/01, we initiated a programmatic change in our primary surgical approach to advanced gynecologic malignancies using extensive upper abdominal procedures to achieve maximal cytoreduction. We reviewed the records of all pts with advanced ovarian, tubal or peritoneal carcinoma who underwent primary cytoreduction at our institution between 1/01 and 4/05. Results: The study cohort included 277 pts. Primary disease site was: ovary; 232 (84%); tubal, 9 (3%); and peritoneum, 36 (13%). Stage was: IIIA, 6 (2%); IIIB, 12 (4%); IIIC, 215 (78%); and IV, 44 (16%). Tumor grade was: I, 6 (2%); II, 30 (11%), III, 235 (85%), and unknown, 6 (2%). Cytoreductive outcome was: no gross residual disease (RD), 68 (25%); ≤ 1 cm RD, 153 (55%); and &gt; 1 cm RD, 56 (20%). There was no threshold CA-125 level that accurately predicted cytoreductive outcome. With CA-125 values &gt; 500 U/mL, 50% (57/113) of pts required extensive upper abdominal surgery to achieve RD ≤ 1 cm, compared to 27% (25/93) for those with CA-125 &lt; 500 U/mL (P = 0.03). The table demonstrates the number of pts cytoreduced to = 1 cm RD in relation to preoperative serum CA-125 and the proportion of pts who needed extensive upper abdominal surgery to achieve this degree of cytoreduction. Conclusions: After the incorporation of extensive upper abdominal procedures, preop CA-125 did not predict the primary cytoreductive outcome of pts with advanced ovarian, tubal or peritoneal carcinoma. With preoperative CA-125 &gt; 500 U/mL, extensive upper abdominal procedures were necessary in 50% of pts to achieve residual disease ≤ 1 cm. These data may be useful as part of preoperative surgical counseling and planning. [Table: see text] No significant financial relationships to disclose.

A single arm, multicenter, open label, phase II study of lapatinib as 2L treatment of pts with locally advanced/metastatic transitional cell carcinoma (TCC) of the urothelial tract

4594 Background: Lapatinib is an oral reversible inhibitor of ErbB1 (EGFR) and ErbB2 (HER-2/neu) receptor tyrosine kinases. Methods: The primary endpoint was RECIST response rate. Key eligibility criteria included stage IIIB/IV TCC of the bladder, progression following a first-line platinum regimen, expression of ErbB1 and or ErbB2 (1, 2 or 3+ by IHC) and KPS ≥ 70. Lapatinib (1250 mg, qd) was administered until disease progression or unacceptable toxicity. Tumor and safety assessments were performed every 8 and 4 wks, respectively. Cardiac function was monitored at baseline and every 8 wks. Tumor tissue was analyzed for biomarkers (TUNEL, p53, pAkt, Her3, pHer3, pErk, IGF-1R, Rb, pS6). Results: Fifty-nine pts were enrolled. Investigators reported 2 (3%) PRs and 12 (20%) SD; independent radiologic review (IRR) reported 1 (2%) PR and 18 (31%) SD. Based upon investigator and IRR, six and three pts had durable SD lasting 4 and 6 mos, respectively. At wk 8, 10 pts had some degree of cytoreduction; however, most was short-lived. One pt remains on study for > 56 wks. The median TTP was 8.6 wks (95% CI, 8.00, 11.29) and median OS was 17.9 wks (95% CI, 13.14, 30.29). A trend towards clinical benefit was observed in pts with 2+/3+ ErbB1 or ErbB2. Preliminary analysis of biomarkers suggests high pHer3, high pErk and both mutant p53 and high pHer3 predicts resistance, and high pAkt and high IGF-1R predicts sensitivity to lapatinib. Adverse events (AEs) with ≥ 10% frequency were diarrhea (39%), rash (32%), nausea (27%), vomiting (22%), asthenia (12%) and fatigue (10%). Grade 3/4 AEs occurring in more than one pt were vomiting (7%) and diarrhea (3%). One pt had an asymptomatic, Grade 2 decrease in LVEF. Conclusions: Lapatinib was well-tolerated and exhibits activity in pts with relapsed, advanced/metastatic TCC of the bladder, demonstrated by clinical benefit (CR + PR + SD≥ 16 wks) in 14% and 12% of pts by investigator and IRR, respectively. The median TTP of 8.6 wks is comparable to reports of various 2L chemotherapies. There was a trend toward clinical benefit in pts with ErbB1 or ErbB2 2+/3+ by IHC. Multivariate analysis of the biomarker data is planned. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GlaxoSmithKline GlaxoSmithKline GlaxoSmithKline

Therapeutic leukapheresis in hyperleucocytic leukaemias: lack of correlation between degree of cytoreduction and early mortality rate

The clinical and laboratory data of 48 leukapheresis-treated patients with hyperleucocytic leukaemia (HL) was reviewed to assess the correlation between the degree of leucoreduction and early mortality. Leukapheresis resulted in > 50% leucoreductions and postapheresis WBC counts < 100 x 10(9)/l in most patients (64.5%). Patients presenting with neurological, respiratory or renal complications had higher early mortality rates than patients without such complications, despite similar initial WBC counts and comparable leucoreductions. Thus, in these patients, more efficient leucoreduction was not associated with improved early survival.

The evaluation of low-dose cytarabine in the treatment of myelodysplastic syndromes: a phase-III intergroup study

One hundred and forty one patients were treated in a combined Eastern Cooperative Oncology Group and Southwest Oncology Group phase-III study evaluating low-dose cytarabine (LDAC) versus supportive therapy for the treatment of myelodysplastic syndrome (MDS). Patients were randomized to either cytarabine 10 mg/m2 subcutaneously BID or supportive therapy. Central pathology review was required. All patients were classified according to the FAB criteria for MDS. The overall concordance rate for the MDS subtype was 52%, and 25 patients were pathology exclusions, including 20 with AML. The overall response rate to a single cycle of LDAC was 32%, with 11% complete and 21% partial responses. The median duration of response was 5.9 months, with a range of 1.4-33.5 months. Responses were seen in all subtypes. Infections were more common in the LDAC arm. There was no difference in the time to progression or the overall survival for patients treated with LDAC or supportive therapy. The incidence of leukemic transformation was similar in both arms at 15%, but it differed according to the MDS subtype. Patients receiving LDAC had a decreased transfusion requirement after 3 months. There was a significant correlation between the degree of cytoreduction after receiving a single cycle of LDAC and survival. This survival difference was most marked in patients with the RAEB and RAEB-T subtypes. Although LDAC produced responses in all subtypes of the MDS, there was no effect on overall survival or transformation to AML. However, selected patients benefited from a single cycle of LDAC with durable responses. A cytoreductive effect appears to be required for a durable response. Future studies should include pathology review and must address the clinical and biological heterogeneity of MDS.