Secondary Debulking Surgery Research Articles

Rectal lymph node metastasis in recurrent ovarian carcinoma: essential role of 18F-FDG PET/CT in treatment planning

Although uncommon, ovarian cancer cells may spread to the rectal lymph nodes. However, few reports have described how to detect and treat such metastases. We report a case of a 59-year-old woman with mesorectal and pararectal lymph node metastases in recurrent ovarian carcinoma, detected conclusively using 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT), and treated by low anterior resection with total mesorectal excision aiming for macroscopic complete resection. The treatment goals for the patient were gradually changed from curative to palliative chemotherapy; she survived for 45 months without rectal obstruction after secondary debulking surgery, and was followed up until autopsy. Thus, 18F-FDG PET/CT may be valuable for detecting rectal lymph node metastasis and can play an essential role in planning treatment for recurrent ovarian carcinoma.

Abstract PR15: Autologous whole-tumor antigen combinatorial immunotherapy for recurrent ovarian cancer.

Abstract Novel therapeutic strategies are warranted in recurrent ovarian cancer. We report two independent consecutive studies of combinatorial immunotherapy comprising dendritic cell (DC)-based autologous whole tumor antigen vaccination in combination with antiangiogenesis therapy. Twenty-one patients with recurrent progressive stage III and IV ovarian cancer with available tumor lysate from secondary debulking surgery enrolled in two different studies. First 6 underwent priming with intravenous bevacizumab and oral metronomic cyclophosphamide (bev/cy x 2 doses), followed by vaccination with an autologous DC preparation pulsed with freeze-thaw autologous tumor lysate while the other fifteen underwent vaccination with an enhanced more immunogenic vaccine where autologous DCs were loaded with HOCl-oxidized autologous tumor lysate administered intranodally every 2 weeks in combination with intravenous bev. Both studies were followed by lymphodepletion using high-dose outpatient cyclophosphamide and fludarabine and transfer of 5-30 x10e9 autologous vaccine-primed, ex vivo CD3/CD28-costimulated peripheral blood T cells, in combination with antiangiogenesis therapy and vaccination. Feasibility, safety, and biological and clinical efficacy were evaluated. Eight subjects have completed vaccination and T cell transfer to date, while thirteen additional subjects completed vaccination only. Vaccination was well tolerated and produced limited grade 1 toxicities and elicited tumor-specific T cell responses against various ovarian tumor antigen in both studies and clinical responses correlated with the immune response with ~66% of patients achieving clinical benefit with some experiencing prolonged progression free survival and remission inversion. Following lymphodepletion, adoptive transfer of vaccine-primed, CD3/CD28-costimulated autologous T cells produced grade 1 toxicity and resulted in durable reduction of CD4+FoxP3+ T regulatory cells, increased total lymphocyte counts and restoration of vaccine-induced antitumor immunity in patients who experienced clinical benefit at end of study. One patient exhibited no evidence of disease at end of study. Stable disease was observed in three subjects to date. Interestingly in a subject where adoptive T cell transfer was not followed by restoration of vaccine-induced antitumor immunity, disease progression was observed. Data on additional patients will be presented at the meeting. Our results suggest the use of combinatorial cellular immunotherapy comprising DC vaccination with whole tumor antigen and adoptive lymphocyte transfer using tumor antigen-specific T cells for the treatment of patients with recurrent ovarian cancer is promising yet warrants further investigation. This abstract is also presented as Poster A30. Citation Format: Lana E. Kandalaft, Janos Tanyi, Cheryl Lai-Lai Chiang, Drew Torigian, Daniel J. Powell, Jr., George Coukos. Autologous whole-tumor antigen combinatorial immunotherapy for recurrent ovarian cancer. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; Dec 2-5, 2012; Miami, FL. Philadelphia (PA): AACR; Cancer Res 2013;73(1 Suppl):Abstract nr PR15.

Treatment and prognostic analysis of ovarian cancer patients with isolated region of lymph node recurrence

To evaluate the management and survival of lymph node region recurrence of epithelial ovarian cancer (EOC), and discuss its suitable therapeutic strategy. Thirty-eight patients with the recurrence of lymph node region were extracted from 1945 patients who were diagnosed EOC and treated in Sun Yat-sen University Cancer Center from January 1995 to December 2008. The clinical characteristics, therapy methods and survival of them were retrospectively analyzed. Patient age at initial diagnosis was > 50 years old in 24 patients and ≤ 50 years old in 14 patients. There were 15 cases with stage II and 23 cases with stage III in terms of initial International Federation of Gynecology and Obstetrics (FIGO, 1987) staging. Classified with histological grade, 7 cases were in G(1), 14 cases were in G(2), 17 cases were in G(3); according to the histological types, 19 cases were with serous adenocarcinomas, and 19 cases were with non-serous adenocarcinomas (including 9 endometrioid adenocarcinoma, 1 mucinous adenocarcinoma and 9 unclassified adenocarcinoma). The median follow-up time was 59 months (ranged 16 to 124 months). (1) Feature of recurrences: the median interval of last treatment to recurrence was 18 months (range 9 to 96 months). Most of them were absence of symptoms. The serum level of CA(125) was elevated in 15 patients (39%, 15/38). (2) Treatment of recurrences:of the 38 patients, 19 underwent lymphadnectomy for recurrence regions and received adjuvant chemotherapy (surgery + chemotherapy group), 14 received local radiotherapy and adjuvant chemotherapy (radiotherapy + chemotherapy group), 5 received chemoherapy only (chemotherapy group). There were 35 cases achieved complete response (CR), including 19 patients underwent secondary debulking surgery in surgery + chemotherapy group, 14 cases in radiotherapy + chemotherapy group (12 of them treated by radiotherapy, the other 2 cases reached CR after adjuvant chemotherapy) and 2 cases in chemotherapy group. While only 3 patients reached partial response in chemotherapy group. (3) Survival and second recurrences: during follow-up, 14 cases died of tumor, 4 cases survival with tumor while 20 cases survival without evidence of tumor. The 5-year post-recurrence survival rate of 38 cases was 66.5%, with 71.8%, 68.8% and 40.0% in surgery + chemotherapy, radiotherapy + chemotherapy, and chemotherapy group, respectively, and there was no significant difference in survival rate between them (P > 0.05). A total of 15 patients experienced second recurrences, including 7 cases with peritoneal and 8 cases with lymph node region recurrences. (4) Prognosis factors: the univariate analysis shown that survival after recurrence was significantly related to patient age, tumor-free interval and number of recurrence disease (P < 0.05), while not to FIGO stage, histological type, histological grade, and lymphadnectomy during primary surgery (P > 0.05). The multivariate analysis showed that patient age and tumor-free interval were independent prognostic variables for survival after recurrence (P < 0.05). The lymph node region recurrence of EOC may be have good prognosis and distinctive clinical process. Local treatment strategies including secondary surgery and radiotherapy should be considered, which may significantly improve survival in ovarian cancer patients with lymph node region recurrence.

Association of SNP genotype in ABCB1 with completion of intraperitoneal chemotherapy in ovarian and primary peritoneal cancer.

5077 Background: A standard of care (SOC) for the adjuvant treatment of ovarian and primary peritoneal cancer is a platinum-based intravenous (IV) chemotherapy doublet. Intraperitoneal (IP) chemotherapy is also a SOC, but the high incidence of grade 3/4 adverse events has limited its acceptance among clinicians. To identify genetic markers for completion of IP chemotherapy, we analyzed SNPs in four genes known to play a role in metabolism of platinum or taxane drugs. Methods: Patients diagnosed with primary or recurrent stage III or IV epithelial ovarian or primary peritoneal cancer who had primary or secondary debulking surgery at Mayo Clinic (Rochester, MN) between January 2007 and February 2009 followed by IP chemotherapy were included in this study. A cycle was defined as IV paclitaxel (135mg/m2) on day one, IP cisplatin (100mg/ m2) on day two, and IP paclitaxel (60mg/ m2) on day eight. With prior consent from the patient, peripheral blood was obtained before treatment for extraction of germline DNA. Using a custom Illumina BeadXpress 96-plex panel, SNPs in GSTM1 (N=7), ABCB1 (N=57), CYP3A4 (N=7), and CYP2C8 (N=25) were genotyped. The association between SNPs in these subsets of genes and completion of IP chemotherapy was analyzed using linear regression. Results: Thirty-seven patients were included in this study and 16 (43.2%) completed IP chemotherapy. Twenty-two out of the fifty-seven ABCB1 SNP’s were associated with the number of cycles (p&lt;0.15). There were no significant associations for GSTM1, CYP3A4 and CYP2C8 SNP’s. The minor A allele at missense SNP rs2229109 in the ABCB1 gene was present in five (31.2%) who completed treatment and only one (4.8%) who did not (p&lt;0.007). However, the later was due to catheter complication. There was no association between rs2229109 and overall or progression-free survival. Conclusions: Our findings suggest that SNP rs2229109 in ABCB1 gene is associated with completion of IP chemotherapy, and potentially, less toxicity from chemotherapy. Thus, these patients may be optimal candidates for IP chemotherapy. Further studies in a larger population are needed.

Using hospital claims data to identify ovarian cancer recurrence: A validation study.

e15513 Background: The use of administrative hospital claims data in research studies offers a promising alternative to conducting expensive chart abstraction to assess utilization and health outcomes. However, the validity of using claims data to capture ovarian cancer recurrence is unknown. Methods: We used two strategies to identify recurrent ovarian cancer: 1) a previously validated algorithm of secondary malignancy diagnosis codes used to identify recurrent breast cancer, adapted to ovarian cancer and 2) a new algorithm we created based on the timing and utilization of secondary chemotherapy or secondary debulking surgery for ovarian cancer. To identify secondary debulking surgery, which does not have its own billing code, weobtained codes used by gynecologic oncology billers from across the nation to identify these procedures. We identified all ovarian cancer patients who had undergone primary debulking surgery followed by initiation of primary chemotherapy at a single academic medical institution in NYC, between 2003 and 2010. We then ran the two recurrence algorithms on this population and randomly selected a sample of 50 patients to assess the sensitivity and specificity of each algorithm versus gold-standard chart abstraction data. Results: When applied to our sample of ovarian cancer patients, the sensitivity of the previously validated algorithm was 91% (95% CI: 57% to 99%), the specificity was 28% (95% CI 16% to 45%), the PPV was 26% (95% CI: 14% to 43%) and the NPV was 92% (95% CI: 66% to 99%). In contrast, the sensitivity of our newly developed algorithm to detect ovarian cancer recurrence based on hospital claims data was 100% (95% CI: 68% to 100%), the specificity was 87% (95% CI: 72% to 95%), the PPV was 69% (95% CI: 41% to 88%) and the NPV was 100% (95% CI: 87% to 100%). Conclusions: An algorithm culled from billers and clinical experts identifying timing and utilization of procedures measured ovarian cancer recurrence with a greater degree of accuracy than a previously validated algorithm to detect cancer recurrence. When complex chart reviews are not feasible, our claims-based algorithm can be used by researchers to answer important questions about ovarian cancer treatment effectiveness.

A novel autologous oxidized whole-tumor antigen vaccine therapy for recurrent ovarian cancer.

5023 Background: Despite surgical and chemotherapeutic advances, the death rate from ovarian cancer has not changed. We report here an enhanced dendritic cell vaccine platform developed for clinical testing. Furthermore we report the application of this novel platform comprising of dendritic cell (DC)-based autologous whole tumor antigen vaccination in a pilot study of patients with recurrent ovarian cancer. Methods: To determine the optimal tumor lysate preparation for loading DCs, ovarian tumor lines were prepared by HOCl-oxidation, UVB-irradiation or freeze and thaw. Normal donor DCs were evaluated for tumor lysate uptake, cytokine and chemokine productions and phenotype. The optimal lysate preparation, was used in a phase I study where five patients with recurrent ovarian cancer with available tumor lysate from secondary debulking surgery underwent intranodal vaccination with OC-DC, an autologous DC preparation pulsed with HOCL oxidized autologous tumor cells. Feasibility, safety, and biological and clinical efficacy were evaluated. Results: Normal donor DCs pulsed with HOCl-oxidized tumor lines demonstrated the highest tumor lysate uptake, matured efficiently after LPS and IFN-gamma stimulation, and produced higher levels of proinflammatory cytokines and chemokines. In vitro, these lysates loaded DCs primed T cell responses against ovarian tumor associated antigens and effectively expanded against tumor specific T cells from donors and patients. Therapy was feasible and well tolerated in all subjects. Vaccination with OC-DC produced limited grade 1 toxicities and elicited tumor-specific T cell responses. Moreover specific HLA-A2-restricted responses were documented following vaccination and HER-2/neu specific T cells were expanded following 10 days of in vitro culture. Patients exhibiting immune response demonstrated clinical benefit including two patients who demonstrated remission inversion on vaccine maintenance. Conclusions: We developed a DC-HOCl oxidized whole tumor lysate vaccine which was safe and well-tolerated by patients. The vaccine was highly proinflammatory and elicited cellular and humoral anti-tumor responses establishing a platform for immune-combinatorial therapy.

Secondary cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for recurrent epithelial ovarian cancer: a multi‐institutional study

Please cite this paper as:Deraco M, Virzì S, Raspagliesi F, Iusco D, Puccio F, Macrì A, Famulari C, Solazzo M, Bonomi S, Grassi A, Baratti D, Kusamura S. Secondary cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for recurrent epithelial ovarian cancer: a multi‐institutional study. BJOG 2012;119:800–809.Objective To assess the efficacy and morbidity and mortality of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in recurrent epithelial ovarian cancer (EOC).Design A retrospective study conducted using information extracted from a multi‐institutional prospective database on peritoneal surface malignancies (PSMs).Setting Four Italian centres specializing in locoregional treatment of PSM.Population Patients with recurrent EOC.Methods Fifty‐six patients underwent 57 combined procedures. CRS was performed using peritonectomy procedures and HIPEC using the closed‐abdomen technique with cisplatin and doxorubicin or cisplatin and mitomycin‐C.Main outcome measures Overall survival (OS), progression‐free survival (PFS), morbidity and mortality rates.Results The median age of the patients was 55.2 years (range 30–75 years). The median peritoneal cancer index was 15.2 (range 4–30). Forty‐seven patients had microscopic residual disease (completeness of cytoreduction, CC‐0), seven had residual disease ≤2.5 mm (CC‐1) and one had residual disease &gt;2.5 mm (CC&gt;2). Major complications occurred in 15 patients (26.3%), and procedure‐related mortality occurred in three patients (5.3%). The median follow‐up time was 23.1 months. The median OS and PFS were 25.7 (95% CI 20.3–31.0) and 10.8 (95% CI 5.4–16.2) months, respectively. The 5‐year OS and PFS were 23% and 7%, respectively. Independent prognostic factors affecting OS according to the multivariate analysis were Eastern Cooperative Oncology Group performance status, preoperative serum albumin, and completeness of cytoreduction.Conclusions Patients with recurrent EOC treated with CRS and HIPEC showed promising results in terms of outcome. The combined treatment strategy could benefit subsets of patients wider than that defined for conventional secondary debulking surgery without HIPEC. These data warrant further evaluation in randomised clinical trials.

Abstract LB-133: Vaccination with dendritic cells pulsed with autologous oxidized whole tumor lysate induced strong and long-lasting anti-tumor immunity in recurrent ovarian cancer patients

Abstract Background Despite surgical and chemotherapeutic advances, the death rate from ovarian cancer has not changed over the past two decades. We report here an enhanced, more rapid and more immunogenic dendritic cell vaccine platform developed for clinical testing. Furthermore we report the application of this novel immunotherapy platform comprising of dendritic cell (DC)-based autologous whole tumor antigen vaccination in a pilot study of patients with recurrent ovarian cancer. Methods To determine the optimal tumor lysate preparation for loading DCs, ovarian tumor lines (SKOV3, OVCAR5 and A1847) were prepared by HOCl-oxidation, UVB-irradiation or freeze and thaw. Normal donor DCs were evaluated for tumor lysate uptake, cytokine and chemokine productions and phenotype after maturation with lipopolysaccharides (LPS) and interferon (IFN)-gamma. The optimal lysate preparation, was used in a phase I study where five patients with recurrent, progressive stage III and IV ovarian cancer with available tumor lysate from secondary debulking surgery underwent intranodal vaccination with OC-DC, an autologous DC preparation pulsed with HOCl-oxidized autologous tumor cells (5-10 x 106 DC per dose, 5 doses). Feasibility, safety, and biological and clinical efficacy were evaluated. Results Normal donor DCs pulsed with HOCl-oxidized tumor lines demonstrated the highest tumor lysate uptake, matured efficiently after LPS and IFN-gamma stimulation, and produced higher levels of proinflammatory cytokines and chemokines including IL-1, IL-6, IL-8, IL-12, IP-10, MIP-1alpha and MIG. In vitro, these lysates loaded DCs primed T cell responses against ovarian tumor associated antigens and effectively expanded against tumor specific T cells from donors and patients. Therapy was feasible and well tolerated in all five subjects. Vaccination with OC-DC produced limited grade 1 toxicities and elicited tumor-specific T cell responses. Moreover specific HLA-A2-restricted responses to HER-2/neu, MUC1, NYESO-1, mesothelin and WT1 were documented following vaccination and HER-2/neu specific T cells were expanded following 10 days of in vitro culture. Patients exhibiting immune response demonstrated clinical benefit including two patients who demonstrated remission inversion on vaccine maintenance. Conclusions We developed a DC-HOCl oxidized whole tumor lysate vaccine which was safe and well-tolerated by all patients. The DC vaccine was highly proinflammatory and elicited cellular and humoral anti-tumor responses establishing a platform for immune-combinatorial therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-133. doi:1538-7445.AM2012-LB-133

Intraperitoneal Chemotherapy for Recurrent Epithelial Ovarian Cancer Is Feasible With High Completion Rates, Low Complications, and Acceptable Patient Outcomes

Three large randomized clinical trials have shown a survival benefit for patients treated with intraperitoneal (IP) compared with intravenous chemotherapy for advanced stage epithelial ovarian cancer (EOC). However, the use of IP chemotherapy in recurrent EOC is controversial. The purpose of this study was to determine outcomes, completion rates, and frequency of complications in patients with platinum-sensitive recurrent EOC treated with IP chemotherapy. A retrospective, single-institution analysis of women who received IP chemotherapy for recurrent EOC from January 2003 to April 2010 was conducted. Study patients were identified from the Tumor Registry and office records. Demographic factors, stage, histology, surgical findings, cytoreduction status, and subsequent therapies were abstracted. Progression-free (PFS) and overall survival (OS) were estimated by Kaplan-Meier methods. Fifty-six women who received IP chemotherapy for their first EOC recurrence were identified. The mean age of patients was 56.7 years (range, 40-79 y). Fifty-five patients (98.3%) had previously completed at least 6 cycles of intravenous chemotherapy. Of all patients, 87.5% were initially diagnosed with advanced stage disease (stage IIA-IV). All patients underwent secondary cytoreduction at the time of IP port placement. Moreover, 67.9% of patients were considered optimally cytoreduced (<1 cm residual disease) at the end of the secondary debulking surgery. Forty-two patients (75%) were able to successfully complete at least 6 cycles of IP chemotherapy. Reasons for noncompletion were disease progression, allergic reaction, renal failure, pain, severe nausea and vomiting, death, and patient refusal. Six patients (10.7%) developed port complications including pain around port site, port malfunction, and port erosion into small bowel. Median PFS since the initiation of IP chemotherapy was 10.5 months (95% confidence interval, 7.5-16.4 months) and median OS was 51 months (95% confidence interval, 40.8-61.1 months). Intraperitoneal chemotherapy is a feasible option for patients with recurrent EOC, with high completion rates, low frequency of complications, and acceptable PFS and OS.

Extended duration of response with second-line intraperitoneal platinum-based therapy for epithelial ovarian cancer.

5073 Background: For epithelial ovarian cancer (EOC), a longer duration of response after second-line intravenous (IV) therapy as compared to first-line (IV) platinum therapy occurs in only 3% of patients (Markman et al., 2004). The purpose of this study was to examine the time to progression interval (TPI) in patients treated with surgery and intraperitoneal (IP) chemotherapy for first recurrence of their disease. Methods: We retrospectively reviewed the medical records at our institution for women treated with second-line IP chemotherapy between January 2005 and April 2010. TPI was defined as the time from the end of previous therapy to the start of next therapy for both first-line and second-line platinum therapy. Results: We identified 56 women who received second-line IP chemotherapy for their EOC recurrence. All patients had previously undergone primary surgical cytoreduction (82.3% were considered optimally cytoreduced) followed by IV platinum-based chemotherapy. The mean age was 56.7 years (range 43-79). All patients underwent secondary cytoreduction at the time of IP port placement for treatment of recurrent disease and 65.3% of patients were considered optimally cytoreduced (< 1 cm residual disease) at the end of the secondary debulking surgery. In 13 patients (23.2%) a longer TPI after second-line IP chemotherapy was observed compared to TPI after primary IV chemotherapy. The median first-line TPI for those 13 women was only 8 months, while median TPI after second-line IP chemotherapy was 24 months. In comparison, the 43 patients with shorter TPI after IP chemotherapy had median TPI of 22.5 mos after first-line IV chemotherapy and 8 months after IP chemotherapy. Conclusions: A longer duration of second-line response was observed in 23.2% of patients treated with IP chemotherapy after IV chemotherapy and the duration of response was clinically significant. The use of IP platinum treatment for recurrent EOC should be further studied in a prospective trial in women who do not do receive front-line IP platinum chemotherapy.

Incidental events of diaphragmatic surgery in 82 patients with advanced ovarian, primary peritoneal and fallopian tubal cancer

Surgical resections, such as peritoneal stripping (peritonectomy) are performed for disseminated diaphragmatic lesions of advanced ovarian cancer. This study retrospectively investigated the incidental events of diaphragmatic surgery. The records of patients with advanced mullerian carcinomas, including ovarian, primary peritoneal and fallopian carcinomas, who underwent diaphragmatic surgery were reviewed. Based on our criteria, stripping was performed for surface disease on the diaphragm, and full-thickness resection was performed for bulky disease. In certain cases, both procedures were performed. We analyzed intra- and post-operative incidental events in 82 patients. The χ(2) and Fisher's exact tests were used in the statistical analysis. There were 82 stage III-IV cases of which 56 patients underwent stripping, 12 underwent full-thickness resection and 14 patients underwent both procedures. Unexpected open chest surgery following stripping occurred in 1 out of 63 patients (1.6%) in the primary, 4 out of 13 patients (30.8%) in the interval and 0 out of 6 patients (0.0%) in the secondary debulking surgery groups. The incidence of unexpected open chest surgery was high in the interval debulking surgery group (p<0.001). Regarding post-operative events, accumulation of pleural effusion was identified in 43 patients (52.4%). The incidence of pleural effusions was not significantly different between the two procedures. No complications were encountered, nor was a chest tube required, during unexpected open chest surgery and postoperative pleural effusions. Therefore, it was concluded that special attention should be paid during interval debulking surgery even though it was possible for surgical resections of diaphragmatic lesions to be performed safely.

Lymph Node Involvement in Epithelial Ovarian Cancer

To perform a cartography of lymph node metastases in epithelial ovarian cancer and to determine predictive factors of lymph node metastases. The charts of 355 patients with epithelial ovarian cancer who underwent lymphadenectomy during a primary (n = 252) or secondary debulking surgery (n = 103) were analyzed. The topography of the lymph node metastases was notified for the whole group according to the stage of the disease, the histological type, and the moment of surgery. In patients who underwent a primary surgery before chemotherapy, independent prognostic variables for the risk of lymph node involvement were tested with a multivariate analysis. Independent prognostic factors were combined to determine risk profiles in individual patients. The main area of the lymph node metastases was para-aortic. Isolated pelvic lymph node involvement was 10%. Three variables independently predicted lymph node invasion: advanced T stage, high-risk histological profile, and metastases. When lymphadenectomy is recommended, systematic lymph node dissections in the aortic and pelvic areas are warranted. An isolated pelvic lymph node assessment, particularly in the early stages, is inappropriate. By combining independent risk factors, a useful tool for individual risk assessment of lymph node involvement could be established, helping to decide whether to perform a lymph node dissection, especially at restaging surgery.

Small cell carcinoma of the ovary: clinical and biological study

Ovarian small cell carcinoma of hypercalcemic type is a rare neoplasm that typically occurs in young females. We describe three cases of ovarian small cell carcinoma of hypercalcemic type occurring in patients aged 24, 37, and 25 years. The first patient had stage IIc disease and had primary surgery with a left salpingo-oophorectomy and omentectomy, followed by chemotherapy with cisplatin and etoposide. Upon a second relapse, pelvic lymphadenectomy was performed, followed by chemotherapy with docetaxel. She is alive for 4 years without any recurrence after the initial treatment. In vitro drug-sensitivity assay revealed the tumor cells were sensitive to taxane and resistant to irinotecan. The second patient had stage III disease and had primary debulking surgery with bilateral salpingo-oophorectomy, simple hysterectomy, omentectomy, low-anterior resection, and lymphadenectomy, followed by chemotherapy with paclitaxel and carboplatin. Four months after the initial treatment she relapsed and died. The tumor cells were sensitive to platinum, taxane, and doxorubicin, but resistant to irinotecan. The third patient had stage III disease and had right salpingo-oophorectomy, omentectomy, and lymphadenectomy, followed by chemotherapy with cisplatin, cyclophosphamide, and doxorubicin. She relapsed 4 months after completing the chemotherapy and died 5 months after secondary debulking surgery. The tumor cells were sensitive to platinum, taxane, and doxorubicin, but resistant to irinotecan. The drug-sensitivity assays suggested that a non-irinotecan, taxane-containing combination might have been suitable as first-line chemotherapy for these patients. However, an effect of such a regimen was seen in only one patient with early-stage disease, and this questions the validity of chemosensitivity testing.

Folate receptor alpha as a tumor target in epithelial ovarian cancer

Objectives. Folate receptor α (FRα) is a folate-binding protein overexpressed on ovarian and several other epithelial malignancies that can be used as a target for imaging and therapeutic strategies. The goal of this study is to improve historical data that lack specific information about FRα expression in rare histological subtypes, primary disease versus metastatic foci, and recurrent disease. Methods. FRα expression was analyzed by immunohistochemistry on 186 primary and 27 recurrent ovarian tumors, including 24 pairs of samples obtained from the same individuals at diagnosis and at secondary debulking surgery. For 20 of the 186 primaries, simultaneous metastatic foci were also analyzed. FRα staining was analyzed in light of disease morphology, stage, grade, debulking status, and time from diagnosis to recurrence and death. Results. FRα expression was apparent in 134 of 186 (72%) primary and 22 of 27 (81.5%) recurrent ovarian tumors. In 21 of 24 (87.5%) matched specimens, recurrent tumors reflected the FRα status detected at diagnosis. Metastatic foci were similar to primary tumors in FRα staining. FRα status was not associated with time to recurrence or overall survival in either univariate or multivariable analyses. Conclusion. FRα expression occurs frequently, especially in the common high-grade, high-stage serous tumors that are most likely to recur. New findings from this study show that FRα expression is maintained on metastatic foci and recurrent tumors, suggesting that novel folate-targeted therapies may hold promise for the majority of women with either newly diagnosed or recurrent ovarian cancer.

Hand reconstruction with lobulated combined flaps based on the circumflex scapular pedicle

Repair of multiple soft tissue defects on hand often pose a difficult problem to the reconstructive surgeons with employing a limited number of reliable flaps and recipient vessels. This report is to explore the feasibility and advantage of the treatment of multiple soft tissue defects on hand with combined island flaps based on branches of the circumflex scapular system. From 2002 to 2006, nine patients had transfer of the scapular lobulated combined flaps based on the transverse branch, ascending branch, and descending branch of the circumflex scapular vascular pedicle for coverage of soft-tissue defects over injured hands. Follow-up ranged from 6 months to 24 months with average 12.1 months' all of nine flaps completely survived without complications. Arterial insufficiency was found in one flap because of the pedicle compression in the subcutaneous tunnel. The blood supply to flap was restored after the compression was released. All transferred flaps showed good appearance without significantly swelling and congestion. Two flaps underwent secondary debulking surgery. At 6 months postoperatively, partial protective sensation (S1) was restored in the flaps. The donor sites were directly closed in six cases. Skin grafts were used to cover the donor sites in other three cases. All of donor sites healed without complications. Our report shows that the management of multiple soft tissue defects on hand in complex hand injuries with lobulated flaps of circumflex scapular system can obtain good results for its good appearance and low donor site complications. It is probably the optimal surgical intervention for these injuries.

Recurrent epithelial ovarian cancer (EOC): What determines the outcome?

15003 Background: Recurrent EOC is a common clinical problem and treatment is not curative. We retrospectively analyzed the data on 354 patients with recurrent EOC to determine the impact of various prognostic factors on outcome. Methods: Between August, 1989 and June, 2005, 354 patients (median age 49 years, range, 28 to 80 years) were diagnosed as recurrent EOC. 259 patients received chemotherapy alone, 44 were treated with combination of secondary debulking surgery and chemotherapy or radiotherapy. Remaining 51 (14.4%) patients had no treatment. Main types of salvage chemotherapy included- cisplatin + cyclophosphamide (CP, n = 53), CP + adriamycin (CAP, n = 68), paclitaxel + carboplatin/cisplatin (TP, n = 78). 10 factors were analyzed for survival. Results: 56.5% of patients responded to chemotherapy; complete (CR)-34.2% and partial response (PR) in 22.3% of patients. 124 (35%) patients had no response or progressive disease. 10 (2.8%) died of chemo-toxicity and in remaining 20 status was not known. Median overall survival for patients who received treatment is 19 months vs 3 months for 51 patients who did not receive treatment, p &lt; .001. Predictors of survival were - response to salvage chemotherapy (20 vs 8 months, p &lt; .001), treatment-free interval (&gt;6 months vs ≤ 6 months, 23 vs 9 months p &lt; .001), site of relapse (single vs multiple, 22 vs 16 months, p &lt; .001), Chemotherapy regimen (CP vs CAP vs Paclitaxel + carboplatin) p &lt; .003 on univariate analysis. Age (≤50 years vs &gt;50 years, p = 0.02), initial stage (I vs II vs III vs IV, p = 0.079), histology (serous vs others, p = 0.849), site of relapse (vault vs others, p = 0.156) were not significant predictors. On multivariate logistic regression analysis- response to salvage chemotherapy (HR 0.21, 95% CI 0.15–0.30), treatment-free interval (HR 0.36, 95% CI, 0.20–0.64), and site of relapse (vault vs others, HR 1.22, 95% CI 0.78–1.94) attained significance among 10 factors analyzed. Conclusions: Present study confirms that all patients with recurrent EOC should receive treatment. Response to salvage chemotherapy, a longer treatment-free interval (&gt;6 months) and single site of metastasis are predictors of significantly superior outcome. No significant financial relationships to disclose.

Salvage whole-abdominal radiation therapy after second-look laparotomy or secondary debulking surgery in patients with ovarian cancer

Salvage whole-abdominal radiation therapy after second-look laparotomy or secondary debulking surgery in patients with ovarian cancer

Salvage whole-abdominal radiation therapy after second-look laparotomy or secondary debulking surgery in patients with ovarian cancer

Objectives. Our aim was to determine the outcomes associated with use of whole-abdominal radiation therapy (WART) in women with ovarian cancer, to identify predictors of response, and to assess associated toxicity. Methods. From 1981 through 2000, 171 women received WART at our institution after ovarian cancer surgery. Relevant clinical information was extracted through retrospective chart review. Results. One hundred nine patients received WART after positive second-look laparotomy (SLL), and 62 were treated after secondary debulking (SD) for recurrent disease. The median dose to the whole abdomen was 25.5 Gy (range, 1.0–30.5 Gy). Therapy included a pelvic boost in 120 patients (70%) and a para-aortic boost in 21 patients (12%). The planned radiation course was completed in 123 patients (72%). In the SLL group, 5-year survival was 29% with a median follow-up of 98.4 months. The 5-year progression-free survival (PFS) was 41% in those with microscopic disease. There was one treatment-related death (1%). For the SD group, median PFS was 11 months and associated with treatment-related mortality in 5%. Overall, treatment-related small bowel obstruction occurred in 26 patients (15%). Conclusions. In patients with a positive SLL, WART should be considered only for those with microscopic residual disease. Treatmentrelated small bowel obstruction can be expected in 15% of these patients. Use of WART for recurrent disease appears to be related to serious bowel toxicity in 5% with an associated short disease-free interval; the therapeutic index of WART may not be acceptable in patients with

Salvage whole-abdominal radiation therapy after second-look laparotomy or secondary debulking surgery in patients with ovarian cancer

Objectives Our aim was to determine the outcomes associated with use of whole-abdominal radiation therapy (WART) in women with ovarian cancer, to identify predictors of response, and to assess associated toxicity. Methods From 1981 through 2000, 171 women received WART at our institution after ovarian cancer surgery. Relevant clinical information was extracted through retrospective chart review. Results One hundred nine patients received WART after positive second-look laparotomy (SLL), and 62 were treated after secondary debulking (SD) for recurrent disease. The median dose to the whole abdomen was 25.5 Gy (range, 1.0–30.5 Gy). Therapy included a pelvic boost in 120 patients (70%) and a para-aortic boost in 21 patients (12%). The planned radiation course was completed in 123 patients (72%). In the SLL group, 5-year survival was 29% with a median follow-up of 98.4 months. The 5-year progression-free survival (PFS) was 41% in those with microscopic disease. There was one treatment-related death (1%). For the SD group, median PFS was 11 months and associated with treatment-related mortality in 5%. Overall, treatment-related small bowel obstruction occurred in 26 patients (15%). Conclusions In patients with a positive SLL, WART should be considered only for those with microscopic residual disease. Treatment-related small bowel obstruction can be expected in 15% of these patients. Use of WART for recurrent disease appears to be related to serious bowel toxicity in 5% with an associated short disease-free interval; the therapeutic index of WART may not be acceptable in patients with recurrent disease regardless of the degree of cytoreduction.

Role of Surgery in Ovarian Cancer: An Update

Rupture of an ovarian malignant tumor should be avoided at the time of surgery for an early ovarian cancer. Laparoscopic removal of ovarian cysts should be restricted to patients with preoperative evidence that the cyst is benign. Degree of differentiation is the most important independent prognostic factor in stage I disease and should be used in decisions on therapy in clinical practice and the future FIGO-classification of Stage I. In early ovarian cancer staging adequacy and tumor grade were the only 2 statistical significant prognostic factors for survival in the multivariate analysis of the EORTC ACTION-trial. According to the present data there is no scientific basis to rely only on adjuvant chemotherapy or on optimal staging procedure in medium and high risk stage I ovarian cancer. Primary debulking surgery by a gynecologic oncologist remains the standard of care in advanced ovarian cancer. Optimal debulking surgery should be defined as no residual tumor load. Interval debulking is defined as an operation performed after a short course of induction chemotherapy, usually 2 or 3 cycles. Based on the randomized EORTC-GCG trial, interval debulking by an experienced surgeon improves survival in some patients who did not undergo optimal primary debulking surgery. Based on the GOG 152 data, interval debulking surgery does not seem to be indicated in patients who underwent primarily a maximal surgical effort by a gynecological oncologist. Open laparoscopy is probably the most valuable tool for evaluating the operability primarily or at the time of interval debulking surgery. In retrospective analyses neoadjuvant chemotherapy followed by interval debulking surgery does not seem to worsen prognosis compared to primary debulking surgery followed by chemotherapy. However, we will have to wait for the results of the EORTC-GCG/NCI Canada randomized trial to know whether neoadjuvant chemotherapy followed by interval debulking surgery is as good as primary debulking surgery in some or all stage IIIc and IV patients. The most suitable candidates for secondary debulking surgery are those who had an initial complete response to chemotherapy, a long treatment-free interval (e.g. more than 12 months), and resectable disease (without diffuse carcinomatosis).