Stage IIB Patients Research Articles

Association between Pretreatment Levels of Serum Vascular Endothelial Growth Factor (VEGF) and Survival Outcomes in Locally Advanced Cervical Cancer Patients

Objective: To evaluate the association between pretreatment levels of serum vascular endothelial growth factor (VEGF) and long-term treatment outcomes in patients with locally advanced cervical cancer (LACC). Methods: Thirty-nine patients diagnosed with LACC (stage IIB-IVA) and obtaining blood for serum VEGF were identified. All patients received complete treatment as radical radiotherapy with or without concurrent chemotherapy. Surveillance for all patients was every 3 months during the first 2 years, and every 6 months later. Results: Mean age of 39 patients was 52.3 ± 10.8 years old. Twenty-three patients (59.0%) had stage IIB, and 16 patients (41.0%) had stage IIIB. Histological cell type was mostly squamous cell carcinoma (89.7%). The median and 75th percentile level of serum VEGF were 610.2 pg/ml (0.0 - 4067.2 pg/ml) and 825.6 pg/ml, respectively. At median follow-up of 37.0 months (range, 26.8 - 46.3 months), the 3-year OS rate was 78.6%. Clinical stage (p = 0.04) and 75th percentile of VEGF level (p = 0.04) were impacted on OS in univariable analysis. The 3-year OS of patients in stage IIB with serum VEGF of ≤825.6 pg/ml and of > 825.6 pg/ml was slightly different, 94.4% and 80.0% respectively (p = 0.34), whereas there were many differences in stage IIIB, 71.4% and 25.0% in patients with serum VEGF of ≤825.6 pg/ml and of >825.6 pg/ml respectively (p = 0.05). Conclusion: High pretreatment serum VEGF level has an influence on OS for LACC. It is potentially used as a predictive factor, especially in patients stage IIIB, in order to provide efficient treatment and improve survival outcomes in the future.

Incidence of lymph node metastases in locally advanced cervical cancer in figo stage ib2-iib - the role of preoperative radiotherapy

This study aims at determining the incidence rate, number, location and type of lymph node metastases in patients with cervical cancer in stage IB2 and IIB as classified by FIGO prior to and after radiotherapy. Between 2003 and 2011, 184 patients with cervical cancer in FIGO clinical stage IB2-IIB were operated on in the Clinic of Gynaecology, St. Anna University Hospital of Varna. Surgery consisted in radical hysterectomy type III and LEP procedure in most cases. Radiotherapy was performed either preoperatively 30 Gy TGT and postoperatively until 52 Gy, or postoperatively - 52 Gy TGT. All the patients were divided into 4 groups according to the stage and order of procedures: group one - 83 patients in stage IB2 with primary surgery; group two - 11 patients in stage IB2 with preoperative radiotherapy and surgery; group three - 31 patients in stage IIB with primary surgery, and group four - 50 patients in stage IIB with preoperative radiotherapy and surgery. The incidence rate of lymph node metastases in these groups was 37.3%, 9%, 38.7%, and 22%, respectively. The incidence rate of macro metastases in lymph nodes in these groups was 20.4%, 9%, 25.8%, and 12%, respectively. Preoperative radiotherapy reduced the incidence rate of lymph node metastases in locally advanced cervical cancer in FIGO stage IB2-IIB. In these patients, lumbosacral, pre-sacral, and para-aortic lymph node dissection should be performed alongside the pelvic lymph node dissection to minimize the risk of distant metastases. The lymph node dissection occupied a central place in the surgical treatment of these patients. In addition to its therapeutic effects, it played a staging role that determined the most appropriate adjuvant treatment. Scripta Scientifica Medica 2012; 44(2): 65-67.

Abstract A19: miR-19a modulates chemoradiotherapy resistance in human cervical cancer

Abstract Cervical cancer is one of the most common cancers in women worldwide. Advanced uterine cervical squamous cell carcinomasuterine (UCSCC) patients in FIGO stage IIb or IIIb treated with platinum based concomitant chemoradiotherapy. However, clinical outcomes vary significantly and are difficult to predict. Tumor intrinsic chemoradiotherapy sensitivity is one of the crucial reasons for concomitant chemoradiotherapy failure in UCSCC. In this study, we identified the relationship between miR-19a and sensitivity to concomitant chemoradiotherapy. The UCSCC patients in FIGO stage IIb or IIIb treated with platinum based concurrent chemoradiotherapy at the Cancer Institute and Hospital, Chinese Academy of Medical Sciences. Patients with progressive disease during first line platinum based chemotherapy or those who suffered recurrent disease within 6 months of completing first line therapy were termed resistant. Patients without recurrence or with recurrences beyond 6 months were termed sensitive. We examined the expression level of miR-19a in 30 cervix biopsies samples, including 10 resistant and 20 sensitive samples. We found miR-19a was significantly up-regulated in resistant group compared with sensitive group (p <0.05). Our study indicated that miR-19a might be a marker to identify cervical cancer patients who are likely to fail concomitant chemoradiotherapy. To verify role of miR-19ain cervical cancer cells is worthy of further investigation. Citation Format: Mei Liu, Lingying Wu, Ningzhi Xu, Jusheng An, Jinlong Hu, Manni Huang, Binbin Tu, Chenfei Hu, Zaozao Wang, Hongxia Zhu. miR-19a modulates chemoradiotherapy resistance in human cervical cancer. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr A19.

CXCR4 Expression Predicts Early Liver Recurrence and Poor Survival After Resection of Pancreatic Adenocarcinoma

OBJECTIVES:Liver metastasis develops in 60% of patients after resection of pancreatic adenocarcinoma (PAC) and carries a dismal prognosis, but factors predictive of liver recurrence are poorly understood. Experimental evidence suggests that liver metastasis of PAC is mediated by CXCL12/CXCR4 signaling and can be inhibited by CXCR4 antagonist. We aimed to verify whether CXCR4 expression predicts early liver recurrence and poor survival after resection, and to explore the usefulness of CXCR4 status for prognosis prediction.METHODS:Ninety-seven consecutive PAC patients undergoing R0 resection were analyzed. CXCR4 expression was analyzed by immunohistochemistry, and its associations with liver recurrence-free survival and overall survival were analyzed by Kaplan–Meier estimates and multivariable Cox and accelerated failure time regression models.RESULTS:CXCR4-positive patients had a worse prognosis than CXCR4-negative patients, with a shorter liver recurrence-free survival (median: 8.7 vs. 39.7 months; P=0.004) and overall survival (median: 10.2 vs. 22.3 months; P<0.001). Overall survival for CXCR4-positive stage IIa patients was similar to that for stage IIb patients and significantly shorter than that for CXCR4-negative stage IIa patients (median: 9.7 vs. 27.4 months; P=0.002). CXCR4 positivity was significantly associated with liver recurrence (adjusted hazard ratio 2.22, 95% confidence interval (CI) 1.15–4.30; P=0.018) and predicted a 46% (95% CI 9–68%) and 35% (95% CI 7–54%) reduction in liver recurrence-free survival and overall survival, respectively.CONCLUSIONS:Tumor CXCR4 expression independently predicts early liver recurrence and poor overall survival after resection of PAC. CXCR4 status stratifies stage IIa patients into two groups with a striking difference in prognosis.

Clinical impact of 18F-FDG PET/CT on initial staging and therapy planning for breast cancer

The purpose of this study was to determine the clinical significance of 18F-FDG PET/CT on initial staging and therapy planning in patients with invasive breast cancer. One hundred and forty-one consecutive, biopsy proven preoperative and 195 postoperative high-risk breast cancer patients who were referred for PET/CT for initial staging were included in this retrospective study. The clinical stage had been determined by conventional imaging modalities prior to the PET/CT scan. Of the 141 examined preoperative patients, 19 had clinical stage I (T1N0), 51 had stage IIA (12 T2N0 and 39 T1N1), 49 had stage IIB (2 T3N0 and 47 T2N1), 12 had stage IIIA (11 T3N1, 1 T2N2), 2 had stage IIIB (2 T4N1) and 8 had stage IV. PET/CT modified the staging for 26% of stage I patients, 29% of stage IIA patients, 46% of stage IIB patients, 58% of stage IIIA patients and 100% of stage IIIB patients. PET/CT scans detected extra-axillary regional lymph nodes in 14 (9.9%) patients and distant metastasis in 41 (29%) patients. PET/CT scans detected multifocal lesions in 30 (21%) patients, multicentric lesions in 21 (14%) patients and malign foci in the contralateral breast (bilateral breast cancer) confirmed by biopsy in 5 (3.5%) patients. Of the examined 195 postoperative patients PET/CT detected axillary lymph nodes in 22 (11%) patients, extra-axillary regional lymph nodes in 21 (10%) patients and distant metastasis in 24 (12%) patients. PET/CT findings altered plans for radiotherapy in 22 (11%) patients and chemotherapy was adapted to the meta-static diseases in 24 (12%) patients. PET/CT was revealed to be superior to conventional imaging modalities for the detection of extra-axillary regional metastatic lymph nodes and distant metastases. These features make PET/CT an essential imaging modality for the primary staging of invasive breast cancer, particularly in patients with clinical stages II and III.

Marginal resection for osteosarcoma: Long-term outcomes.

e20505 Background: When a favorable response to chemotherapy is clinically obtained, we usually perform intentional marginal resection, which preserves the surrounding areas that are normally resected, such as ligament, nerves, blood vessels, and epiphysis region. We report on the long-term outcomes of osteosarcoma patients who underwent the combination therapy and subsequently underwent intentional marginal resection. Methods: The subjects were 43 patients with osteosarcoma. The mean age was 15 years and the mean follow-up period was 101 months. Tumors were Enneking’s surgical stage IIB in 36 patients and IIIB in 7 patients. The patients received preoperatively 3-5 courses of intraarterial fusion of caffeine combined with CDDP and ADM. The effectiveness of chemotherapy was evaluated using plain x-ray, angiography, MRI, and thallium scintigraphy. If the results of two or more imaging examinations showed effectiveness of the treatment, the patient was considered to have a complete response or partial response. Results: The treatment was effective in 14 patients (Grade III) and 29 patients (Grade IV) by histological evaluation (Rosen &amp; Huvos) that correlated with the results of imaging evaluation. Limb function was evaluated according to ISOLS scoring system, excellent is 32 patients (74.4%), good in 7 patients (16.3%), fair in 3 patients (7.0%), and poor in 1 patient (2.3%). Local recurrence was observed in only 2 patients (4.7%). For stage IIB patients, both 5- and 10-year cumulative survival rates were 93.8%. The outcome (IIB + IIIB) was CDF in 26 patients, NED in 8 patients, AWD in 1 patient, and DOD in 7 patients. Conclusions: It is important to minimize surgical margin and to preserve healthy tissue and important structures for improving the function of the affected limb and providing optimal quality of life for the osteosarcoma patients. In the present study, intentional marginal resection was performed in osteosarcoma patients who were clinically obtained favorable responses to a combination of chemotherapy and caffeine administration. They had a good clinical course and there was no negative effect on the survival rate or local recurrence rate.

Dynamic contrast-enhanced ultrasound and transient arterial occlusion for quantification of arterial perfusion reserve in peripheral arterial disease

ObjectiveTo quantify muscular micro-perfusion and arterial perfusion reserve in peripheral arterial disease (PAD) with dynamic contrast-enhanced ultrasound (CEUS) and transient arterial occlusion. Materials and methodsThis study had local institutional review board approval and written informed consent was obtained from all subjects. We examined the dominant lower leg of 40 PAD Fontaine stage IIb patients (mean age, 65 years) and 40 healthy volunteers (mean age, 54 years) with CEUS (7MHz; MI, 0.28) during continuous intravenous infusion of 4.8mL microbubbles. Transient arterial occlusion at mid-thigh level simulated physical exercise. With time–CEUS–intensity curves obtained from regions of interest within calf muscles, we derived the maximum CEUS signal after occlusion (max) and its time (tmax), slope to maximum (m), vascular response after occlusion (AUCpost), and analysed accuracy, receiver operating characteristic (ROC) curves, and correlations with ankle-brachial index (ABI) and walking distance. ResultsAll parameters differed in PAD and volunteers (p<0.014). In PAD, tmax was delayed (31.2±13.6 vs. 16.7±8.5s, p<0.0001) and negatively correlated with ankle-brachial-index (r=−0.65). m was decreased in PAD (4.3±4.6mL/s vs. 13.1±8.4mL/s, p<0.0001) and had highest diagnostic accuracy (sensitivity/specificity, 75%/93%) for detection of diminished muscular micro-perfusion in PAD (cut-off value, m<5∼mL/s). Discriminant analysis and ROC curves revealed m, and AUCpost as optimal parameter combination for diagnosing PAD and therefore impaired arterial perfusion reserve. ConclusionsDynamic CEUS with transient arterial occlusion quantifies muscular micro-perfusion and arterial perfusion reserve. The technique is accurate to diagnose PAD.

P2-09-11: Role of 18FDG-PET/CT in the Staging of Large Primary Operable Breast Cancer.

Abstract Background: Prospective evaluation of the role of 18FDG-PET/CT in patients with large primary operable breast cancer. Material and Methods: During 56 months, consecutive patients with large (&amp;gt;2cm) breast cancer and clinical stage IIA/IIB/IIIA (based on clinical examination, mammography, breast MRI and ultrasonography) underwent 18FDG-PET/CT. The nuclear physician was blind to the results of any other procedure (bone scan, chest X-ray, liver ultrasound, or thoraco-abdominal CT scan). Results: Out of the 131 examined patients, 36 had clinical stage IIA (34 T2 N0, 2 T1 N1), 48 stage IIB (20 T3 N0, 28 T2 N1), and 47 stage IIIA (29 T3 N1, 9 T2 N2, 9 T3 N2). 18FDG-PET/CT modified staging for 5.6% of stage IIA patients, for 14.6% of stage IIB patients, and for 27.6% of stage IIIA patients. However, within stage IIIA, the yield was specifically high among the 18 patients with N2 disease (56% stage modification). When considering stage IIB and primary operable IIIA (T3 N1) together, the yield of 18FDG-PET/CT was 13% (10/77); extra-axillary regional lymph nodes were detected in 5 and distant metastases in 7 patients. In this series, 18FDG-PET/CT outperformed bone scan with only 1 misclassification versus 8 for bone scan (p=0.036). Discussion: 18FDG-PET/CT provided useful information in 13% of patients with T3 N0 / T2 N1 / T3 N1 disease. The yield was more modest in patients with T2 N0 disease. The very high yield in the case of lymph nodes classified N2 demonstrates that stage IIIA comprises two quite distinct groups of patients. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-09-11.

Reduced Intensity of Chemotherapy and PET-Guided Radiotherapy in Patients with Advanced Stage Hodgkin Lymphoma: The GHSG HD15 Final Results

Abstract 589▪FN2▪This icon denotes a clinically relevant abstract Purpose:Intensified chemotherapy with eight cycles of BEACOPPescalated in advanced stage Hodgkin lymphoma (HL) is highly effective but also associated with relevant treatment related toxicity. In addition, the need for radiotherapy in this setting is unclear. To reduce toxicity without losing efficacy the German Hodgkin Study Group thus conducted the prospective randomized clinical HD15 trial investigating two less intensive chemotherapy variants, followed by positron emission tomography (PET) guided radiotherapy. Methods:Between January 2003 and April 2008, 2182 patients with newly diagnosed, histology-proven HL aged 18–60 years were included. Patients in Ann-Arbor stage IIB with large mediastinal mass or extranodal lesions, or those in stage III or IV were randomly assigned to receive either eight cycles of BEACOPPescalated (8Besc), six cycles of BEACOPPescalated (6Besc), or eight cycles of BEACOPP14 (8B14). After completion of chemotherapy, patients in partial response (PR) with a persistent mass measuring 2.5 cm or more were assessed by PET. Only patients who were positive on centrally-reviewed PET scan received additional radiotherapy (RT) with 30Gy. The study was designed to show non-inferiority for the primary endpoint, freedom from treatment failure (FFTF). Other endpoints included overall survival, tumor response, side effects of treatment and progression-free survival (PFS) after PET. Results:The full analysis set comprised 2126 patients, 705 with 8Besc, 711 with 6Besc and 710 with 8B14. Baseline characteristics were balanced between groups with a median age of 33 years and 334 patients (15.7%) in stage II disease. 682 patients (32.1%) had an International Prognostic Score (IPS) of 0–1, 1115 (52.4%) of 2–3, and 329 (15.5%) of 4–7. Hematological toxicities occurred in 92.4% (8Besc), 91.7% (6Besc), and 79.7% (8B14) of cases. After a median follow-up of 48 months, there were 53 deaths (7.5%) in the 8Besc group, 33 (4.6%) in the 6Besc group and 37 (5.2%) in the 8B14 group. The higher number of deaths in the 8Besc group mainly resulted from acute toxicity of chemotherapy (15 vs. 6 vs. 6) and secondary neoplasms (13 vs. 5 vs. 8). There were 72 secondary cancers including 29 secondary acute myeloid leukemias and myelodysplastic syndroms, 19 (2.7%) after 8Besc, 2 (0.3%) after 6Besc and 8 (1.1%) after 8B14. Complete response (CR) was achieved in 90.1% of patients after 8Besc, in 94.2% after 6Besc and in 92.4% after 8B14 (p=0.01). FFTF at 5 years was 84.4% in the 8Besc group, 89.3% in the 6Besc group (97.5% confidence interval (CI) for difference 0.5% to 9.3%), and 85.4% in the 8B14 group (97.5 CI −3.7% to 5.8%), respectively (see figure). Accounting for planned interim analyses, both 97.5 repeated CIs for the hazard ratio excluded the non-inferiority margin of 1.51 (8Besc vs. 6Besc, 0.44 to 1.02; 8Besc vs. 8B14, 0.62 to 1.36). Overall survival at five years was 91.9%, 95.3%, and 94.5%, and was also better with 6Besc compared to 8Besc (97.5% CI 0.2% to 6.5%). PFS results were similar to FFTF. Per-protocol and subgroup analyses supported the primary analysis. PET scans performed after chemotherapy were centrally reviewed in 822 patients of whom 739 were in PR with residual mass ≥ 2.5 cm having no other exclusion criteria. 548 patients were PET-negative (74.2%) and 191 were PET-positive (25.8%). Importantly, PFS was comparable between patients in CR or those in PET-negative PR after chemotherapy with 4-year PFS rates of 92.6% and 92.1%, respectively. Only 11% of all patients in HD15 received additional RT as compared to 71% in the prior HD9 study. Conclusion:Six cycles of BEACOPPescalated followed by PET-guided RT are more effective and less toxic compared to 8 cycles in patients with advanced stage HL. In particular, critical toxicities observed with 8 cycles where reduced with 6 cycles of BEACOPPescalated. PET performed after chemotherapy can guide the need of additional RT in this setting and reduces the number of patients requiring RT. [Display omitted] Disclosures:No relevant conflicts of interest to declare.

Treatment outcomes of concurrent weekly carboplatin with radiation therapy in locally advanced cervical cancer patients

Objective To evaluate treatment outcomes of locally advanced cervical cancer patients who received concurrent weekly carboplatin with radiation therapy. Methods Patients with locally advanced cervical cancer who had primary radiation treatment in concurrent with weekly carboplatin (100 mg/m 2 or AUC 2) from 1997 to 2008 were identified. Demographic data, chemotherapy cycles, total treatment time, toxicities, and treatment outcomes were recorded. Results One hundred and forty-eight patients with stage IIB (50.7%), IIIB (48.0%) and IVA (1.3%) cervical cancer patients were included in the study. Median total treatment time was 53.5 days (range, 45–100 days). Carboplatin was given for a median number of 6 cycles (range, 3–6 cycles). Complete response was achieved in 142 patients (95.9%) while six (4.1%) had persistent diseases. Among the 142 responders, 36 experienced recurrences: pelvic recurrences in seven (4.7%), distant failure in 25 (16.9%), and both pelvic and distant in four (2.7%). The 2-year and 5-year progression-free survival rates were 75.1% and 63.0%, respectively with the corresponding 2-year and 5-year overall survival rates of 81.9% and 63.5%. No grade 3 or 4 hematologic and non-hematologic toxicities were observed during treatment in any patients. Late grade 3–4 gastrointestinal or genitourinary toxicities were 10.1% and 0.7%, respectively. Conclusion Concurrent weekly carboplatin with radiation therapy yields high response rate with modest progression-free and overall survivals in locally advanced cervical cancer. The regimen is feasible with minimal toxicities.

The Yield of 18F-FDG PET/CT in Patients with Clinical Stage IIA, IIB, or IIIA Breast Cancer: A Prospective Study

The purpose of this study was to prospectively evaluate the role of (18)F-FDG PET/CT in patients with stage IIA, IIB, or IIIA breast cancer. During 56 mo, 131 consecutive patients with large (>2 cm) breast cancer and clinical stage IIA, IIB, or IIIA (based on clinical examination, mammography, breast MRI, and ultrasonography) underwent (18)F-FDG PET/CT. The nuclear physician was unaware of the results of any other procedure (bone scan, chest radiography, liver ultrasound, or thoracoabdominal CT scan). Of the 131 examined patients, 36 had clinical stage IIA (34 T2N0 and 2 T1N1), 48 stage IIB (20 T3N0 and 28 T2N1), and 47 stage IIIA (29 T3N1, 9 T2N2, and 9 T3N2). (18)F-FDG PET/CT modified staging for 5.6% of stage IIA patients, for 14.6% of stage IIB patients, and for 27.6% of stage IIIA patients. However, within stage IIIA, the yield was specifically high among the 18 patients with N2 disease (56% stage modification). When considering stage IIB and primary operable IIIA (T3N1) together, the yield of (18)F-FDG PET/CT was 13% (10/77); extraaxillary regional lymph nodes were detected in 5 and distant metastases in 7 patients. In this series, (18)F-FDG PET/CT outperformed bone scanning, with only 1 misclassification versus 8 for bone scanning (P = 0.036). (18)F-FDG PET/CT provided useful information in 13% of patients with clinical T3N0, T2N1, or T3N1 disease. The yield was more modest in patients with stage IIA. The high yield in the case of N2 disease demonstrates that stage IIIA comprises 2 quite distinct groups of patients.

Cost-effectiveness of adjuvant therapy for treatment of stage II colon cancer in patients with diabetes.

421 Background: The decision to treat stage II colon cancer patients with adjuvant chemotherapy involves assessment of life expectancy, risk for recurrent disease, and the potential benefit and likelihood of adverse effects from treatment. This is a challenging task, particularly for patients with pre-existing chronic illnesses such as diabetes, which may increase side effects and potentially lessen response to chemotherapy. Methods: We use the Archimedes Model to analyze cost effectiveness of adjuvant therapy in stage II colon cancer patients with pre-existing diabetes. The Archimedes Model is a large-scale, integrated mathematical model of human physiology, diseases, and healthcare systems, including pathways relating to diabetes, cardiovascular disease, and cancers of the breast, lung, and colon. The colon cancer model is built using the SEER, ACCENT databases and meta-analyses of clinical trials. Costs relating to colon cancer, diabetes and its complications are based on Medicare reimbursement rates. We simulate a trial in which stage II colon cancer patients are subjected to two treatment strategies: no treatment vs. adjuvant chemotherapy by FOLFOX regimen. We report incremental cost-effectiveness ratio (ICER), measured by cost per quality-adjusted life year (QALY) gained, of adjuvant therapy compared with no treatment. Results: Cost effectiveness is strongly dependent on a patient's tumor profile, age and duration of diabetes. For instance, adjuvant therapy saves ∼0.2 QALYs per person in stage IIA patients who are 75 and older and have been diagnosed with diabetes &gt;10 years, at an ICER of &gt;$150,000/QALY gained. In contrast, it saves 1.1 QALYs per person in stage IIB patients aged 60-65, recently diagnosed with diabetes, at an ICER of &lt;$30,000/QALY gained. Results are sensitive to assumptions on efficacy and side effects of chemotherapy in diabetic patients, as well as cost of adjuvant therapy. Conclusions: The current study suggests that the decision to proceed with adjuvant chemotherapy requires careful assessment of severity of diabetes in stage II colon cancer patients with pre-existing diabetes. No significant financial relationships to disclose.

Prognostic Significance of Amplification of thec-MYCGene in Surgically Treated Stage IB-IIB Cervical Cancer

Cervical cancer is the second most common cancer among women world-wide, with about 470,000 newly diagnosed cases and almost 250,000 deaths every year. Furthermore, cervical cancer is the most common cause of death from gynecological malignancy in developing countries. Typically, type III radical hysterectomy (RH) is prescribed for patients diagnosed with stage IB-IIA cervical cancer who can tolerate an aggressive surgical approach, and want to avoid the long-term adverse effects of radiation therapy. For stage IIB patients, radiation therapy has been commonly prescribed. However, in some countries in Europe and Asia, type III radical hysterectomies are prescribed for patients with stage IB-IIB cervical cancer. Various clinico-pathological variables evaluated as possible prognostic factors for survival after RH, including depth of invasion, parametrial margin involvement, pelvic lymph node metastasis, number of lymph node metastases, histological type and pre-treatment squamous cell carcinoma (SQCC)-antigen level, are significant factors for clinical outcome. In addition to these clinico-pathologic variables, increasing attention has focused on various new approaches to molecular and genetic changes in cervical cancer. Molecular and genetic alterations are important in the pathogenesis of cervical cancer, especially in association with human papillomavirus (HPV) infections. One of considerable interest is c-MYC gene status. cMYC activation, triggered by insertion of HPV DNA sequences into near the c-MYC locus, is now regarded to be an important genetic event in cervical oncogenesis, c-MYC gene maps to chromosomal band 8q24, which is reportedly a common site for integration of HPV DNA. Gene amplification is an important mechanism for protein overexpression and oncogene activation in tumor cells. c-MYC amplification is well documented in cervical cancer. Amplification of the c-MYC gene is also addressed in breast cancer, bladder cancer, prostate cancer, and lung cancer. Although strong prognostic impact o f c-MYC gene amplification on histologic grade, disease stage and patients survival have been well documented in certain types of tumors, data on prognostic significance of both gain and amplification of c-MYC is lacking in cervical cancer. Therefore, in this study, we assessed c-MYC gene status in human cervical cancer samples using fluorescence in situ hybridization (FISH) to analyze the relation between c-MYC gene amplification and clinicopathologic factors. The prognostic value Prognostic Significance of Amplification of the c-MYC Gene in Surgically Treated Stage IB-IIB Cervical Cancer

ERCC1 (excision repair cross-complementation group 1) expression as a predictor for response of neoadjuvant chemotherapy for FIGO stage 2B uterine cervix cancer

ObjectivePlatinum-based neoadjuvant chemotherapy for locally advanced cervical cancer has some benefits for patients responding to chemotherapy. However, no validated clinical or biologic predictor of response to this chemotherapy has been identified to date. MethodsWe employ immunohistochemical analysis to determine the expression patterns of the excision repair cross-complementation group1 (ERCC1) protein in pre-treatment cervical biopsy tissue. In total, 43 stage IIB patients had been enrolled in a previous etoposide and cisplatin neoadjuvant phase II clinical trial, allowing comparison of the effects of cisplatin-based neoadjuvant chemotherapy on response in relation to ERCC1 expression. ResultsAmong the 43 patients studied, 34 (79.1%) were positive and 9 (20.9%) were negative for ERCC1. Response to chemotherapy (according to RECIST criteria) was observed in all patients with negative ERCC1 expression. In logistic regression analysis, ERCC1 negativity continued to be an independent predictor for responsiveness to neoadjuvant chemotherapy (p=0.021). Among the pretreatment factors, low ERCC1 expression was a significant prognostic factor of disease-free survival in multivariate analysis (p=0.046). ConclusionsThe ERCC1 expression patterns in pretreatment specimens may thus facilitate the prediction of responses to cisplatin-based NAC. We propose that patients expressing low levels of ERCC1 derive the most benefit from cisplatin-based NAC.

Prognostic value of serial blood S100B determinations in stage IIB–III melanoma patients: A corollary study to EORTC trial 18952

S100B is a prognostic factor for melanoma as elevated levels correlate with disease progression and poor outcome. We determined its prognostic value based on updated information using serial determinations in stage IIb/III melanoma patients.211 Patients who participated in the EORTC 18952 trial, evaluating efficacy of adjuvant intermediate doses of interferon α2b (IFN) versus observation, entered a corollary study. Over a period of 36months, 918 serum samples were collected. The Cox time-dependent model was used to assess prognostic value of the latest (most recent) S100B determination.At first measurement, 178 patients had S100B values <0.2μg/l and 33⩾0.2μg/l. Within the first group, 61 patients had, later on, an increased value of S100B (⩾0.2μg/l). An initial increased value of S100B, or during follow-up, was associated with worse distant metastasis-free survival (DMFS); hazard ratio (HR) of S100B⩾0.2 versus S100B<0.2 was 5.57 (95% confidence interval (CI) 3.81–8.16), P<0.0001, after adjustment for stage, number of lymph nodes and sex. In stage IIb patients, the HR adjusted for sex was 2.14 (95% CI 0.71, 6.42), whereas in stage III, the HR adjusted for stage, number of lymph nodes and sex was 6.76 (95% CI 4.50–10.16). Similar results were observed regarding overall survival (OS).Serial determination of S100B in stage IIb–III melanoma is a strong independent prognostic marker, even stronger compared to stage and number of positive lymph nodes. The prognostic impact of S100B⩾0.2μg/l is more pronounced in stage III disease compared with stage IIb.

In Brief

Background. To examine the efficacy of the Ivor Lewis esophagogastrectomy for esophageal carcinoma prior to the widespread use of preoperative chemotherapy and irradiation, we reviewed our experience.Methods. We reexamined the cases of 220 consecutive patients who underwent an Ivor Lewis esophagogastrectomy for esophageal cancer from January 1992 through December 1995.Results. There were 196 men (89.1%) and 24 women. Median age was 65 years (range, 29 to 85 years). The results of pathological study showed adenocarcinoma in 188 patients (85.5%), squamous cell carcinoma in 31 (14.1%), and leiomyosarcoma in 1 patient (0.5%). Postsurgical staging was as follows: stage 0 in 10 patients, stage I in 19, stage IIa in 38, stage IIb in 28, stage III in 111, and stage IV in 14. The operative mortality rate was 1.4% (3 patients), and complications occurred in 83 patients (37.7%). Follow-up was 98.6% complete. Median survival for operative survivors was 1.9 years (range, 32 days to 8.7 years). The overall 5-year survival rate was 25.2%; it was 80% for patients in stage 0, 94.4% for those in stage I, 36.0% for those in stage IIa, 14.3% for patients in stage IIb, 10% for those in stage III and 0% for patients in stage IV.Conclusions. Ivor Lewis esophagogastrectomy for esophageal cancer is a safe operation. Long-term survival is stage dependent. The low survival associated with advanced cancers should stimulate the search for effective neoadjuvant therapy.

Radiochemotherapy versus chemotherapy in locally advanced cervix cancer: A pilot study.

e15561 Background: Many reports have correlated 1) hypoxia with attenuated responses to radiotherapy and 2) a good oxygenation as function of high HGB level in the peripheral blood. There is agreement to increase to the response to the radiotherapy of head and neck with the use of erythropoietin to increase the hemoglobin level. Methods: From January 2002 until January 2009 we treated 88 patients with cervix locally advanced, 26 patients in stage IIB, 28 in stage IIIA 20 in stage III B and 14 patients in IV stage. 44 patients previously treated with chemotherapy (cisplatin, ifosfamide, paclitaxel), the response of chemotherapy was 12 PR,7NC,3 PD. All patients had an HGB between 9 and 12 gr/dL and from 2 weeks before radiotherapy we daily treated with erythropoietin 10,000 UI to increase HGB between 13 and 14 gr/dL, then we gave erythropoietin every day with radiotherapy. In the second group 44 patients were treated with radiotherapy plus 5FU 1g/sm/day, days 1-5, continuous iv infusion + carboplatino 80 mg and erythropoietin. Results: We have analyzed the patients one month after radiotherapy we valued the result of the treatment. Only in 28 /44 patients we used to increase the HGB to 13-14 gr, in the other 8 patients (37% ) the value of HGB was between 9-11 gr. The response to radiotherapy was 26 PR, 16 NC and 2 PD. The response of the second treatment was 15 CR,7 PR. In 8/44 we used to interrupt treatment for III grade of leuko-thrombocytopenia. Conclusions: In patients, previously treated with chemotherapy, the residual disease is probably hypoxic and therefore is radio-resistant for this reason does not increase the efficacy of radiotherapy nonstante the value of HGB between 13-14 gr, after chemotherapy we had a compromised bone marrow hence we coclude that it is difficult to increase the value of hgb after chemotherapy for bone marrow failure. We are continuing the radiotherapy in concomitant with 5FU plus carboplatin and erytropoeitin in the first choice of treatment of cervix cancer locally advanced seeing the good response 30/44 patients with complete response and 14 /44 partial response No significant financial relationships to disclose.

Prognostic Significance of the Number of Lymph Nodes Examined in Colon Cancer Surgery

To identify an optimal cutoff value for the number of lymph node examined (NLNE) to distinguish the prognoses in patients following a curative resection for advanced colon cancer, to clarify the mechanism of the difference, and to suggest the integration of NLNE to colon cancer staging. A total of 859 patients who had undergone surgical treatment for localized colon cancer from 1980 to 2000 were reviewed. This was a cohort from a single institution with mean NLNE of 20.7 and more than 12 NLNE in 77% of the patients. The optimal breakpoint for NLNE was calculated by a receiver operating characteristic curve (ROC) analysis. The patients were stratified into groups based on various parameters and underwent univariate and multivariate analyses with respect to survival. The ROC analysis identified NLNE as a significant prognostic factor with cutoff value of 18 for node-negative and 20 for node-positive patients. A multivariate analysis with these cutoff values identified NLNE as a significant prognostic factor independent of tumor depth and the number of lymph nodes involved. The 5-year cause-specific survival of stage IIB patients was 96.5% with 18 or more NLNE and 67.5% with NLNE less than 18 (P[r]=0.0067). Similarly, a cutoff value of 20 NLNE for node-positive patients separated the 5-year cause-specific survival of stage IIIB patients into 79.3% with 20 or more NLNE and 63.3% with less than 20 NLNE (P=0.0052). The clinical significance of NLNE is not limited to being a benchmark for quality care, but has a definite benefit as a prognostic indicator across the stages. Patients could be stratified more efficiently by the integration of NLNE to TNM staging.

Treatment of nontraumatic osteonecrosis of the femoral head using bone impaction grafting through a femoral neck window

Nontraumatic osteonecrosis of the femoral head (non-ONFH) is a disorder that can lead to femoral head collapse and the need for total hip replacement. Various head-preserving procedures have been used for this disease to avert the need for total hip replacement. These include various vascularised and nonvascularised bone grafting procedures. We examined the effect of bone-grafting through a window at the femoral head-neck junction known as the "light bulb" approach for the treatment of osteonecrosis of the femoral head with a combination of demineralised bone matrix (DBM) and auto-iliac bone. The study included 110 patients (138 hips; 41 females, 69 males; mean age 32.36 years, range 17-54 years) with stage IIA-IIIA nontraumatic avascular necrosis of the femoral head according to the system of the ARCO (Association Research Circulation Osseous). The bone grafting procedure is called "light bulb" procedure in which the diseased bone was replaced by a bone graft substitute (combination of DBM and auto-iliac bone).The outcome was determined by the changes in the Harris hip score, by progression in radiographic stages, and by the need for hip replacement. The mean follow-up was 25.37 months (range 7-42 months). All data were processed by a statistics analysis including Cox risk model analysis and Kaplan-Meier survival analysis. Pre- and postoperative evaluations showed that the mean Harris hip score increased from 62 to 79. Clinically, 94 of 138 hips (68%) were successful at the latest follow-up, and radiological improvement was noted in 100% of patients in stage IIA, 76.67% of patients in stage IIB and 50.96% of patients in stage IIC and IIIA cases. Excellent and good results according to the Harris score were obtained in 100% of cases in stage IIA, 93.33% in stage IIB and 59.62% in stages IIIA and IIC stage, with a survivorship of 85% in stages IIA and IIB and 60% in stage IIIA and IIC cases. Cox risk model analysis showed that the clinical success rate correlated with both pre-operation stage and the necrotic area of the femoral head. The complications included ectopic ossification, lateral femoral cutaneous nerve lesion and joint infection. This procedure may be effective at avoiding or forestalling the need for total hip replacement in young patients with early to intermediate stages of osteonecrosis of the femoral head. Therefore, it may be the treatment of choice particularly in nontraumatic osteonecrosis of the femoral head of pre-collapse stage with small and middle area (<30%, or the depth of collapse <2 mm).

Eight cycles of BEACOPP escalated compared with 4 cycles of BEACOPP escalated followed by 4 cycles of BEACOPP baseline with or without radiotherapy in patients in advanced stage Hodgkin lymphoma (HL): Final analysis of the HD12 trial of the German Hodgkin Study Group (GHSG)

8544 Background: The GHSG HD9 trial had established BEACOPP escalated (BE) as new standard of care for advanced-stage HL patients. The successor study, HD12, evaluated a possible reduction in toxicity by comparing 8 cycles of BE with 4 cycles BE followed by 4 cycles BB. The second question in this trial related to the need of additional radiotherapy (RT) to initial bulk and residual disease. Methods: HL patients in stage IIB with large mediastinal mass and/or E-lesions or stage III/IV were randomised according to a 2x2-factorial design between: 8BE + RT, 8BE no RT, 4BE+4BB + RT, 4BE+4BB no RT. Primary endpoint of the trial was FFTF. Between 9/1999 and 1/2003, a total of 1,670 patients aged 16–65 were randomized. For this final analysis at a median follow up of 78 months, 99 patients were excluded for various reasons resulting in 1,571 eligible patients. Results: Patient characteristics in the 4 groups were comparable. Treatment-related toxicity of WHO grade III/IV was observed in 97% of patients. Most prominent differences between pooled chemotherapy arms were anemia (65% 8BE vs 51% 4BE+4BB) and thrombopenia (65% vs 51%). Treatment outcome: complete remission 92.4%; early progression 2.2%; progression/relapse 7.8% (6.6% and 8.5%). A total of 156 (9.9%) deaths (72 vs 84) have been observed (22 vs 32 acute or salvage treatment toxicity; 15 vs 24 HL; 22 vs 13 secondary neoplasia). Most treatment related deaths occurred in the &gt;60 years age group, the first 4 cycles and the IPS&gt; 3 RF groups. Secondary neoplasias were observed in 77 patients (4.9%). At 5 years, OS was 91%, FFTF 85.5% and progression free survival (PFS) 86.2% (Kaplan-Meier estimates). Estimates for the difference at 5 years are 1.8% for OS, 2.3% for FFTF and 2.7% for PFS favoring BE. However, there was no statistical difference between 8x BE and 4BE+4BB in all outcome parameters (p&gt;0.19, log rank test). There is also no significant difference between the RT or no-RT arms in this study. Conclusions: The adoption of 4BE+4BB as a new standard in the future GHSG studies will depend on a refined analysis of the total data set and will be presented. No significant financial relationships to disclose.