Time Of First Recurrence Research Articles

Recurrent craniopharyngioma after conformal radiation in children and the burden of treatment.

In this paper the authors present their experience treating children with recurrent craniopharyngioma who were initially managed with surgery followed by conformal radiation therapy (CRT). A departmental oncology information system was queried to identify all children (< 18 years old) who received CRT for a craniopharyngioma between 1998 and 2010 (inclusive) and specifically those who experienced tumor progression. For each patient, the authors recorded the type of recurrence (solid, cystic, or both), the time interval to first progression and each subsequent progression, the associated treatment complications, and disease status at last follow-up evaluation. Among the 97 patients that met criteria for entry into this study, 18 (18.6%) experienced tumor progression (9 cystic, 3 solid, 6 cystic and solid). The median time to first recurrence was 4.62 years (range 1.81-9.11 years). The subgroup included 6 female and 12 male patients with a median age of 7.54 years (range 3.61-13.83 years). Ten patients experienced first progression within 5 years of CRT. The 5- and 10-year treatment-free survival rates for the entire cohort were 89.0% (95% confidence interval [CI] 80.5%-93.9%) and 76.2% (95% CI 64%-85%), respectively. Seven patients had a single episode of progression and 11 had more than 1. The time interval between each subsequent progression was progressively shorter. The 18 patients underwent 38 procedures. The median follow-up duration for this group was 9.32 years (range 4.04-19.0 years). Three patients died, including 1 from perioperative complications. Craniopharyngioma progression after prior irradiation is exceedingly difficult to treat and local control is challenging despite repeated surgical procedures. Given our results, gross-total resection may need to be the surgical goal at the time of first recurrence, if possible. Decompressing new cyst formation alone has a low rate of long-term success.

Dexamethasone intravitreal implant for diabetic macular edema: indications for a PRN regimen of treatment.

To define the mean time of first recurrence of diabetic macular edema (DME) after a single injection of dexamethasone intravitreal implant (DEX-I), reducing the burden of monthly visits during a PRN regimen of treatment. Twenty phakic eyes with DME (12 eyes naïve and 8 eyes with edema persistent after previous treatments) were followed monthly after DEX-I injection until evidence of first recurrence of edema, defined as a change in visual acuity (VA) ≥5 letters and/or in foveal thickness (FT) ≥50 µm. Reaching this point, the eyes were re-treated. Monitored parameters were changes in VA, FT, intraocular pressure (IOP), and lens opacity. Maximal efficacy was registered at month 1, when mean VA improved by 14 letters (19%), FT decreased by 325 µm (43.7%), and in 15 eyes (75%) edema was completely reabsorbed. The mean time of first recurrence was 5.1 months. No statistical difference was found between eyes with naïve or persistent DME. Five eyes needed topical medication for modest temporary IOP increase (21-24 mm Hg) between months 2 and 4. No increase in lens opacities was registered during follow-up. According to the results of this study, the first signs of DME recurrence after DEX-I injection appear at a mean time of 5 months, suggesting that an appropriate and prudent time schedule for a PRN regimen could be limited to monthly tonometry and a first complete examination not before 4 months.

Abstract 1088: Differences in metastatic patterns in relation to time between primary surgery and first relapse from breast cancer suggest synchronized growth of dormant micrometastases

Abstract Purpose Compared with most other cancer types, breast cancer has a long natural history. In cases with delayed relapse, the unlinearity of disease progression indicates the presence of periods of tumor dormancy. Clinical and experimental studies indicate that growth might be induced by a physiological event like tissue injury following surgery. In this study we aimed to quantify size and number of metastatic lesions in relation to time between primary surgery and first relapse. Our goal was to find clinical support for the presence of a systemic synchronizing growth signal. Patients and methods All patients (n=209) recorded with metastatic breast cancer at our department during 2004-9 were identified. 180 cases with measurable metastases according to RECIST 1.1 and no metastases at the time of primary surgery (&amp;lt; 2 months), were evaluable. Number of metastatic lesions as well as size of each lesion was recorded at the time of first recurrence. Standard Deviation (SD) of the lesions sizes in each patient was calculated and served as a marker for variability in the metastatic pattern. Patients with a high SD were assumed to have unsynchronized (individual) growth of lesions, whereas patients with low SD were regarded to have synchronized growth. Results Median number of metastatic lesions at first recurrence was 7 (1- &amp;gt;10). Cases with only 1 metastasis (n=38) were excluded from the analyses on SD. Median SD was 5.4 (0.0 - 58). Low SD was significantly associated with low histological grade in primary tumors (Pearson Chi Square p= 0.002), absence of liver metastases (p= 0.001) and presence of lung metastases (p= 0.02). No significant association was found between SD and ER status, Her2 status, nodal status or stage. There was also no significant association between nodal status and time to recurrence (TTR). Patients were grouped according to TTR into two groups; early (&amp;lt; 3years-) or late (&amp;gt; 3 years- after primary diagnosis). In the subgroup of patients that were lymph node negative at primary diagnosis (N0), the median SD was significantly lower in the early group (3.0) when compared with the late group (5.7)(Mann-Whitney U test p= 0.02). This effect was not present in the lymph node positive (N1) patients. Conclusions Our data indicate the presence of a metastatic phenotype characterized by multiple, similar sized metastases. The results support synchronized growth of dormant micrometastases in some cases of breast cancer. The fact that this effect was only present in lymph node negative patients, suggests that micrometastatic tumor dormancy is especially important in this group, with otherwise favorable prognosis. Systemic effects of growth factors released during wound healing following surgery might induce a switch from the dormant state into simultaneous growth of occult micrometastases. Further studies to explore these mechanisms are ongoing. Citation Format: Hanna Dillekås, Monica Transeth, Martin Pilskog, Jörg Assmus, Oddbjorn Straume. Differences in metastatic patterns in relation to time between primary surgery and first relapse from breast cancer suggest synchronized growth of dormant micrometastases. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1088. doi:10.1158/1538-7445.AM2014-1088

Prognostic Factors in 401 Elderly Women with Metastatic Breast Cancer

Background: Elderly patients with metastatic breast cancer have a prognosis and outcome that may be dependent on a host of factors. Patients and Methods: We retrospectively analyzed 401 female breast cancer patients who developed metastatic disease after the age of 70 years in order to define potential prognostic factors for specific survival at the time of first recurrence. Results: With a median follow-up of 60 months from the time of recurrence, the median specific survival was 21.0 months (95% CI 17.0-23.0). In multivariate analysis we demonstrated that negative hormonal receptor status (p = 0.002), presence of positive lymph nodes at initial cancer diagnosis (hazard ratio, HR = 1.37; 95% CI 1.07-1.75; p = 0.01), site of metastasis (p < 10^-4) and metastasis-free interval (HR = 0.99; 95% CI 0.95-0.99; p = 0.008) constituted unfavorable independent prognostic factors able to predict specific survival from the time of metastatic occurrence. Age at initial diagnosis, Scarff-Bloom Richardson grade and adjuvant treatments were significant only in univariate analysis. Conclusion: These survival prognostic factors associated with the use of a specific geriatric questionnaire to assess frailty may assist physicians in evaluating the patient's survival potential and choose a tailored treatment to this cancer population.

Big Data and Clinical Research in Oncology: The Good, the Bad, the Challenges, and the Opportunities

National cancer registries provide an ever-growing volume of data and increasing access to that data for the purpose of clinical research in oncology. In the United States, three national cancer-specific registries have been developed to collect data on cancer patients, their cancers, how they are treated, and their outcomes. Beginning with the passage of the National Cancer Act of 1971 and funded since 1973, the National Cancer Institute (NCI)’s Surveillance Epidemiology and End Results (SEER) program is a population-based registry from 20 U.S. geographic areas, covering *28 % of the U.S. population. In 1989, the American College of Surgeons (ACoS) Commission on Cancer (CoC) started a joint program with the American Cancer Society: the National Cancer Data Base (NCDB). Approximately 70 % of all new cancer cases diagnosed in the United States each year are currently captured by the NCDB, which contains the records of *29 million patients from *1,500 institutions (making the NCDB a hospitalbased, not population-based, registry). Finally, the National Program of Cancer Registries (NPCR) was established in 1992 and is administered by the U.S. Centers for Disease Control and Prevention (CDC). NPCR supports cancer registries in 45 states, representing 96 % of the U.S. population. The data entered into each of these three national cancer registries are not collected completely independently of the others. The processes, system, and rules that govern the data collection for all three registries significantly overlap, as do the professionals (cancer registrars/CTRs) who actually collect and enter the data. The North American Association of Central Cancer Registries Inc. (NAACR), established in 1987, is a collaborative umbrella organization that develops and promotes uniform data standards for the cancer registries. All central cancer registries in the United States (and Canada) are members of NAACR, although each registry may require a different subset of data elements to be reported. In this issue of Annals of Surgical Oncology, In et al. from the ACoS CoC and nearby Chicago hospitals, bring to light one of several important weaknesses of the data currently collected and reported in these national cancer registries: accurate information on local, regional, and distant recurrence rates and the timing of those recurrences after a first course of treatment is completed. The authors point out that the data reported by each of these registries have traditionally concentrated on the initial presentation and first course of treatment, with little follow-up information reliably collected, except death. The NCDB does attempt to collect data on the time of first recurrence as well as the type of recurrence (local, regional, distant), and the authors examined the completeness of these data points in the NCDB for more than 700,000 patients with five common tumor types diagnosed between 2002 and 2005. Disappointingly, they report that complete information to allow an accurate determination if and when a recurrence had occurred after completion of the first course of treatment, and the type of recurrence, was lacking at a majority of the more than 1,400 hospitals for more than half of their patients. On average, hospitals had incomplete recurrence information on 56.7–66.7 % of patients studied. Only 9.0 % of hospitals collected recurrence information well on all five of the cancer sites examined. The absence of reliable information on recurrence after treatment of primary cancer makes the determination of This is an editorial to the article available at doi:10.1245/s10434-0143516-x.

Patterns of Recurrence After Liver Transplantation for Nonresectable Liver Metastases from Colorectal Cancer

BackgroundSurgical resection is the only curative modality for colorectal liver metastases (CLM), and the pattern of recurrences after resection affects survival. In a prospective study of liver transplantation (Lt) for nonresectable CLM we have shown a 5-year overall survival rate of 60 %, but 19 of 21 experienced recurrence. This study reports the pattern of recurrences after Lt for CLM and the effect on survival.MethodsCharacterization of metastatic lesions in a prospective study for Lt for nonresectable CLM was performed (n = 21). The study included reexamination of chest computed tomographic scans taken before Lt.ResultsAt the time of first recurrence, 16 were a single site, and three were multiple sites. Thirteen of the single sites were pulmonary recurrences. The pulmonary recurrences appeared early and were slow growing, and several were accessible to surgical treatment. When chest computed tomographic scans were reexamined, seven patients had pulmonary nodules at the time of Lt without an effect on survival. There was no first single-site hepatic recurrence. Six of the seven patients who developed metastases to the transplanted liver died from metastatic disease.ConclusionsThe pulmonary recurrences after Lt for CLM were of an indolent character, even those that were present at the time of Lt. This contrasts with the finding of metastases to the transplanted liver, which was prognostically adverse. The lack of single hepatic first-site recurrences and hepatic metastases only as part of disseminated disease is different from the pattern of recurrence after liver resection. This suggests two distinct mechanisms for hepatic recurrences after resection for CLM.

Evaluation of post-operative complications associated with repeat resection and BCNU wafer implantation in recurrent glioblastoma

Patients with glioblastoma treated with BCNU wafer implantation for recurrence frequently receive frontline chemoradiotherapy with temozolomide as part of the Stupp protocol. A retrospective investigation was conducted of surgical complications in a cohort of these patients treated at a single institution. We searched our institutional database for patients treated between January 2006 and October 2012 who had recurrent glioblastoma previously treated with open surgery followed by the Stupp protocol and then underwent repeat resection with or without BCNU wafers for recurrent disease. Rates of select post-operative complications within 3 months of surgery were estimated. We identified 95 patients with glioblastoma who underwent resection followed by the Stupp protocol as frontline treatment. At disease recurrence (first and second recurrence), 63 patients underwent repeat resection with BCNU wafer implantation and 32 without implantation. Generally, BCNU wafer use was associated with minor to moderate increases in rates of select complications versus non-implantation-wound healing abnormalities (14.2 vs. 6.2 %), cerebrospinal fluid leak (7.9 vs. 3.1 %), hydrocephalus requiring ventriculoperitoneal shunt (6.3 vs. 9.3 %), chemical meningitis (3.1 vs. 0 %), cerebral infections (3.1 vs. 0 %), cyst formation (3.1 vs. 3.1 %), cerebral edema (4.7 vs. 0 %), and empyema formations (1.5 vs. 0 %). Performance status was well maintained post-operatively in both groups. Median progression-free survival from the time of first recurrence was 6.0 and 5.0 months, respectively. The use of the Stupp protocol as frontline therapy in patients with glioblastoma does not preclude the use of BCNU wafers at the time of progression.

Comparative effectiveness of treatments for recurrent ovarian cancer.

e16551 Background: Traditionally, recurrent ovarian cancer has been treated with chemotherapy. However, increasingly, secondary cytoreductive surgery (SCS) is being performed. We undertook this study to compare survival between SCS vs chemotherapy vs both or neither to treat recurrent ovarian cancer. Methods: Using SEER-Medicare 1997-2007, we identified women age 66+ years with primary late stage epithelial ovarian cancer with fee-for-service Medicare treated with surgery and chemotherapy for their primary cancer who experienced a recurrence. We defined recurrent cancer using claims for chemotherapy, hospice or SCS following a 6 month treatment free window after primary treatment. Survival time is calculated from time of first recurrence. We conducted parametric and semi-parametric multivariate survival analyses to assess comparative treatment survival rates and factors affecting survival. We use propensity score weighting methods to obtain robust estimates of comparative effectiveness. To address the risk that a fraction of patients classified by our algorithms as non-recurrent are, indeed, recurrent, we use finite mixture models. Results: Of the 1,623 women with recurrent cancer, 72% received secondary chemotherapy while 15% receive both chemotherapy and surgery. &lt;2% receive secondary surgery and 12% received hospice with no active treatment. Univariate analyses show that the mean survival time after first recurrence of ovarian cancer is 1,357 days. Multivariate survival models controlling for patient demographics, cancer type and comorbidities show that, compared to patients who received both surgery and chemotherapy, those who received only SCS (-569 days) as well as those who received only chemotherapy (-381 days) had significantly lower survival times. Survival time is negatively associated with black race and age at recurrence and positively associated with date of reoccurrence. Patients with greater comorbidities have significantly shorter survival times. Conclusions: Patients with recurrent ovarian cancer treated with both secondary surgery and chemotherapy survive longer than patients treated with either chemotherapy or surgery. Women who are Black, or older at time of recurrence have worse survival.

Gaining Traction in the Treatment of Adrenocortical Carcinoma

Gaining Traction in the Treatment of Adrenocortical Carcinoma

Reirradiation for recurrent medulloblastoma

Previously irradiated recurrent medulloblastoma (MB) is a highly lethal disease. Reirradiation is often not considered secondary to its potential toxicity and uncertain efficacy. Analysis of retreatment could help identify the feasibility and role of reirradiation for recurrent MB. Thirteen patients who underwent at least 1 course of reirradiation at the authors' institution as a component of management after recurrence were identified, and their medical records were analyzed. At first diagnosis, all patients underwent surgical resection and radiation, with 69% of patients receiving chemotherapy. Median time to initial failure was 50 months (range, 14-103 months). Reirradiation subsite breakdown was as follows: posterior fossa, 46%; supratentorial/whole brain, 31%; spine, 23%; craniospinal, 8%. Median cumulative dose was 84 grays (range, 65-98.4 grays). Of 11 patients completing a full course of reirradiation, there were 6 failures, with 3 in the reirradiation field. Kaplan-Meier estimates of progression-free and overall survival since time of first recurrence were 48% and 65%, respectively at 5 years. Of patients without gross disease at reirradiation, 83% were without evidence of disease at last follow-up. With a median follow-up of 30 months, reirradiation was well tolerated, with only 1 case of asymptomatic, in-field radiation necrosis. The results in this series are promising, but must be interpreted with caution given the limitations. Reirradiation provided most benefit to patients with no evidence of disease after surgical re-resection, and least to patients with gross disease. Important considerations for reirradiation toxicity development include duration between radiation courses and patient age. Further study of reirradiation as part of trimodality therapy is warranted.

Modeling survival in childhood cancer studies using two-stage non-mixture cure models

Non-mixture cure models (NMCMs) are derived from a simplified representation of the biological process that takes place after treatment for cancer. These models are intended to represent the time from the end of treatment to the time of first recurrence of cancer in studies when a proportion of those treated are completely cured. However, for many studies overall survival is also of interest. A two-stage NMCM that estimates the overall survival from a combination of two cure models, one from end of treatment to first recurrence and one from first recurrence to death, is proposed. The model is applied to two studies of Ewing's tumor in young patients. Caution needs to be exercised when extrapolating from cure models fitted to short follow-up times, but these data and associated simulations show how, when follow-up is limited, a two-stage model can give more stable estimates of the cure fraction than a one-stage model applied directly to overall survival.

Irinotecan and BCNU-Impregnated Wafers Used in Combination, for the Treatment of Patients with Recurrent Glioblastoma Multiforme

Introduction: This retrospective study examines the toxicity of the combination of intravenous irinotecan, (CPT-11; Camptosar®; Pharmacia & Upjohn, Kalamazoo, Mich.) and BCNU (1,3-bis(2-chloroethyl)-1-nitrosurea) impregnated wafers (Gliadel®) following implantation at the time of tumor recurrence in patients with glioblastoma multiforme (GBM). Method: Ten patients with recurrent GBM were examined in this study. The inclusion criteria were histologically confirmed GBM, Karnofsky’s Performance Scale (KPS) greater than or equal to 60, and a single focus of recurrent tumor. All patients underwent resection of their tumor at the time of first recurrence with placement of BCNU wafers. Postoperatively, patients were treated with irinotecan. One cycle constituted of 125 mg/m2 once weekly for 4 weeks followed by a 2-week rest. The patients were followed for toxicity, tumor progression and survival. Treatment was discontinued if intolerable side effects ensued. Results: The mean time to tumor progression was 4.35 months. The mean survival from the time of BCNU wafer placement was 12.1 months. The overall mean survival was 18.9 months. The average number of cycles of CPT-11 that patients received was 2.7. The toxicity associated with the CPT-11 was as follows: two patients reported Grade 2 diarrhea and one patient experienced grade 3 pancytopenia, three patients reported deep vein thromboses and one patient suffered a non-life threatening pulmonary embolism. Conclusions: The combination of systemic irinotecan along with local intratumoral BCNU is well tolerated and may be more efficacious than either treatment alone. Our data support the need for a future prospective study designed to confirm the effectiveness of this combined treatment strategy.

Endoscopic Management of Type I Gastric Carcinoid and Recurrence Rate

Background: Type I gastric carcinoids (TIGC) are “rare” neuroendocrine neoplasms arising from ECL cells in the background of atrophic body gastritis, due to gastrin growth effects. Diagnosis is often accidental, as patients may be asymptomatic, and these tumors are usually benign. Data regarding the evolution of TIGC in prospective series are scanty, and thus treatment and follow-up programs are not codified. Aim: To assess the safety of a conservative management of TIGC patients, and their recurrence rate after endoscopic removal. Materials and Methods: We enrolled in this prospective study consecutive patients with TIGC (diagnosis of gastric well-differentiated neuroendocrine tumor associated with atrophic body gastritis) who had at least one gastroscopy after the first diagnosis. Exclusion criteria were treatments other than endoscopical resection (polypectomy or mucosectomy). Results: 29 patients (69% females), median age 65 (23-81), median fasting gastrin 625 pg/ml (43,6-2800; nv<40 pg/ml). 68% had dyspepsia, 76% had anaemia (45% pernicious anaemia). 21 patients (72%) had polypoid carcinoids (median diameter: 6 mm; 2-20) and 8 (28%) had intramucosal carcinoid. Multiple polypoid lesions in 13 patients (45%). Associated severe atrophy in 19 cases (65%), but also mild atrophy in 14%. Median follow-up was 43 months (3-99). No patients died and of the 26 patients who had at least 1 CT-scan or MRI, none had evidence of either local or distant invasion/metastasis. A median of 5 endoscopies performed per patient (2-9) after diagnosis. The recurrence rate of TIGC was 55% (16/29). The median time of first recurrence was 6 (3-54) months from diagnosis; all the patients with recurrence had polyps, 50% multiple. A second recurrence occurred in 10/29 patients (34,5%), after a median of 14,5 (5-51) months from diagnosis and 7 (2-19) from previous carcinoid removal. Neither demographics, biochemical (gastrin, chromogranin-A values)or histological features could distinguish between the 16 recurrent and the 13 non-recurrent patients. Conclusions: TIGC is a benign condition despite the high recurrence rate. Endoscopic polyp removal and subsequent follow-up with is safe and is recommended in the first three years after diagnosis, while radiological evaluation is not necessary.

It's a choice to move forward: women's perceptions about treatment decision making in recurrent ovarian cancer

This research explores the treatment decision-making (TDM) experiences of women with recurrent ovarian cancer (ROC) with regard to treatment options; their understanding of risks and benefits of various treatment options; the decision-making role they want for themselves and for their oncologist; and the social context of the consultation as it pertains to the decision. We conducted semi-structured interviews with 26 women at the time of first recurrence. Through inductive data analysis key themes were identified. Many women describe self-identifying the cancer recurrence fairly quickly due to new symptoms. Many feel that the goal for treating their recurrence is to control versus cure the cancer. They describe the subsequent process of diagnosis and TDM for ROC as quick and straightforward with all women accepting the oncologists' treatment recommendation. They feel that the type and number of treatment options are limited. They have a strong desire for physician continuity in their care. Participants feel that their doctor's recommendations as well as their previous experience with ovarian cancer are strong factors influencing their current TDM process. Shared decision making is based on a simultaneous participation of both the physician and patient in TDM. When faced with ROC, women feel that their doctor's recommendation and their past experience with treatment and TDM are prominent factors influencing the current TDM process.

Oncological Followup After Radical Cystectomy for Bladder Cancer—Is There Any Benefit?

Tumor recurrence after radical cystectomy for bladder cancer can be detected in an asymptomatic patient by regular followup or in a symptomatic patient by symptom guided examination. To our knowledge it is still unknown whether detecting tumor recurrence at an asymptomatic stage offers a better survival rate. A total of 1,270 radical cystectomies for bladder cancer were performed at a single institution between January 1, 1986 and December 2006. All patients had regular followup examinations with chest x-ray and abdominal ultrasound every 3 months, computerized tomography of the abdomen every 6 months, and bone scan and excretory urography every 12 months. Additional examinations were required for symptomatic disease. We analyzed the first site and date of tumor recurrence. Survival was compared using the log rank test. The 20-year recurrence rate was 48.6% in the complete series. Tumor recurrence developed in 444 patients, including 154 asymptomatic and 290 symptomatic patients, with a mean time after radical cystectomy of 20 and 17.5 months, respectively. The most frequent symptoms were pain, ileus, acute urinary retention, hydronephrosis with flank pain, hematuria, neurological symptoms and a palpable mass. Of the 444 patients 182 (41%) had local recurrence and 324 (73%) had distant failure at the time of first recurrence. The overall survival rate 1, 2 and 5 years after first recurrence was 22.5%, 10.1% and 5.5% in asymptomatic patients, and 18.9%, 8.2% and 2.9% in symptomatic patients, respectively (log rank not significant). This study fails to demonstrate a survival benefit for detecting tumor recurrence early at an asymptomatic stage by regular followup examinations. These data show that symptom guided followup examinations may provide similar results at lower cost.

Can Surgical Debulking Reverse Platinum Resistance in Patients With Metastatic Epithelial Ovarian Cancer?

ObjectivesTo examine the impact of delayed primary interval surgical debulking in women with ovarian cancer who show resistance to neoadjuvant platinum-based chemotherapy. MethodsWe carried out retrospective chart reviews to identify women treated for ovarian cancer between 1997 and 2005 who were resistant to neoadjuvant platinum-based chemotherapy based on CA-125 criteria. “Platinum resistance” was defined as having a decrease in serum CA-125 of less than 50% after three cycles of chemotherapy from the time of initial diagnosis. Associations between residual disease and platinum sensitivity status at time of first recurrence were identified using chi-square tests. Median progression-free interval was estimated using the Kaplan Meier method. ResultsNinety-one women were treated with neoadjuvant chemotherapy. Seventeen patients met the criteria for platinum resistance after neoadjuvant chemotherapy. The mean decline in serum CA-125 levels was 18.2%. All patients underwent attempts at surgical debulking. Optimal debulking was achieved in 10 patients (59%). There was a significant association between decreasing amount of residual disease and improving clinical response after primary treatment (P = 0.007), and with platinum sensitivity status at the time of first recurrence (P = 0.023). The estimated median progression free survival was 10.7 months. ConclusionIn women with ovarian cancer who have demonstrated platinum resistance after primary neoadjuvant chemotherapy, optimal tumour debulking can further improve response to subsequent platinum-based chemotherapy and prognosis.

Profile of paliperidone extended release: review of efficacy and safety data

Paliperidone, an active metabolite of risperidone, is the most recent second-generation antipsychotic to become available on the market. This article addresses the pharmacology, clinical efficacy and tolerability of paliperidone. A comprehensive review of studies on MEDLINE using terms, such as paliperidone, 9-hydroxy risperidone, efficacy and tolerability, was conducted. Paliperidone, a 9-hydroxy derivative of risperidone is an antagonist at the dopamine and serotonin receptor sites. As paliperidone is an active metabolite of the parent compound risperidone, it is not metabolized hepatically, has minimal drug–drug interactions and is largely excreted unchanged by the kidneys. It follows linear pharmacokinetics. Evidence from short- and long-term trials supports the efficacy and tolerability of paliperidone extended release (ER) in the treatment of schizophrenia. Randomized, double-blind, placebo-controlled, multicenter studies have demonstrated both paliperidone 6 and 12 mg result in symptom improvement, increase in time of first recurrence of psychotic symptoms as well as significant improvements in personal and social performance. Studies demonstrated increases in plasma prolactin levels and extrapyramidal symptoms with paliperidone ER treatment compared with placebo. Changes in blood glucose and lipid levels with paliperidone ER were comparable to placebo. Overall, paliperidone is an efficacious, well-tolerated addition to the treatment armamentarium for schizophrenia.

The definition of start time in cancer treatment studies analysed by non-mixture cure models

Non-mixture cure models are derived from a simplified representation of the biological process that takes place after treatment for cancer. These models are intended to represent the time from the end of treatment to the time of first recurrence of the cancer in studies when a proportion of those treated are completely cured. However, for many studies, other start times are more relevant. In a clinical trial, it may be more natural to model the time from randomisation rather than the time from the end of treatment and in an epidemiological study, the time from diagnosis might be more meaningful. Some simulations and two real studies of childhood cancer are presented to show that starting from time of diagnosis or randomisation can affect the estimates of the cure fraction. The susceptibility of different parametric kernels to errors caused by using start times other than the end of treatment is also assessed. Analysing failures on treatment and relapse after completing the treatment as two processes offers a simple way of overcoming many of these problems.

The impact of optimal (&lt;1cm) surgical debulking on survival at the time of recurrence in patients with uterine leiomyosarcoma (LMS)

16067 Objective: Uterine leiomyosarcoma (LMS) is an uncommon female malignancy with limited treatment options. To evaluate whether there exists a role for surgery at the time of recurrence, we performed an outcomes analysis from over 25 years of treating LMS at a single institution. Methods: Patients with uterine leiomyosarcoma who presented for treatment at the H. Lee Moffitt Cancer Center from 1981–2005 were identified from the cancer registry database. Patients who underwent surgery (with or without adjuvant treatment) at the time of first recurrence were compared to those patients who did not undergo surgery and were managed medically. Cox regression analysis (multivariate) was used to evaluate whether demographic or pathologic characteristics were associated with survival. Survival curves were estimated using the Kaplan-Meier method and p-values with 95% confidence intervals were generated using the log rank test. Results: Forty-six charts were reviewed to identify forty-one patients with leiomyosarcomas arising from the uterus and treated during 1981–2005. Of the forty-one patients identified, only 7% (N=3) are currently in remission, with a mean follow-up of 40 months from the time of first recurrence. Sixteen patients underwent surgery at the time of first recurrence, with 60% (N=10) of these patients having an optimal cytoreduction (&lt;1cm). On multivariate analysis, post-menopausal status (p=0.011), the presence of tumor necrosis (p=0.038) and high pathologic grade (p=0.056) were significant variables associated with decreased survival. Median survival for optimally cytoreduced patients compared to patients medically managed patients was 55.5 months and 20 months, respectively. A trend towards improved survival in the optimally cytoreduced group was suggested but was not statistically significant (P=0.26) Conclusions: Uterine leiomyosarcoma is a disease with a poor prognosis and a high likelihood of recurrence. We have identified post-menopausal status, tumor necrosis, and pathologic grade as significant predictors of survival. Given the limited treatment options available and with a suggested trend toward improved survival, cytoreductive surgery at the time of recurrence may be worthy of future investigation. No significant financial relationships to disclose.

Risk and Clinical Implications of Transformation of Follicular Lymphoma to Diffuse Large B-Cell Lymphoma

To study the clinical significance of transformation to diffuse large B-cell lymphoma (DLBCL) in patients with follicular lymphoma (FL). From 1972 to 1999, 325 patients were diagnosed with FL at St Bartholomew's Hospital (London, United Kingdom). With a median follow-up of 15 years, progression occurred in 186 patients and biopsy-proven transformation in 88 of the 325. The overall repeat biopsy rate was 70%. The risk of histologic transformation (HT) by 10 years was 28%, HT not yet having been observed after 16.2 years. The risk was higher in patients with advanced stage (P = .02), high-risk Follicular Lymphoma International Prognostic Index (FLIPI; P = .01), and International Prognostic Index (IPI; P = .04) scores at diagnosis. Expectant management (as opposed to treatment being initiated at diagnosis) also predicted for a higher risk of HT (P = .008). Older age (P = .005), low hemoglobin level (P = .03), high lactate dehydrogenase (P < .0001), and high-risk FLIPI (P = .01) or IPI (P = .003) score at the time of first recurrence were associated with the diagnosis of HT in a biopsy performed at that time. The median survival from transformation was 1.2 years. Patients with HT had a shorter overall survival (P < .0001) and a shorter survival from progression (P < .0001) than did those in whom it was not diagnosed. Advanced stage and high-risk FLIPI and IPI scores at diagnosis correlate with an increased risk of HT. This event strongly influences the outcome of patients with FL by shortening their survival. There may be a subgroup of patients in whom HT does not occur.