Results of TRIO-14, a phase II, multicenter, randomized, placebo-controlled trial of carboplatin-paclitaxel versus carboplatin-paclitaxel-ganitumab in newly diagnosed epithelial ovarian cancer.

PURPOSE: Insulin-like growth factor (IGF) signaling is implicated in pathogenesis and chemotherapy resistance of epithelial ovarian cancer (EOC). We explored efficacy and safety of adding ganitumab, a monoclonal antibody targeting IGF-1R, to carboplatin/paclitaxel (CP) chemotherapy in patients with primary EOC. DESIGN: Patients were randomly assigned to receive CP/ganitumab (18 mg/kg q3w) or CP/placebo for 6 cycles followed by 6 cycles of single agent ganitumab/placebo maintenance therapy as front-line therapy. Primary endpoint was progression free survival. Secondary endpoints were time to progression and overall survival. Pretreatment samples were prospectively collected for retrospective biomarker analyses. RESULTS: 170 patients enrolled. 165 patients assessable for toxicity. Median PFS was 15.7 months with CP/ganitumab and 16.7 months with CP/placebo (HR 1.23; 95% CI 0.82-1.83, P = 0.313). All grade neutropenia (84.1% vs 71.4%), thrombocytopenia (75.3% vs 57.1%) and hyperglycemia (15.9% vs 2.6%) were more common in the ganitumab group compared to the placebo group. Ganitumab/placebo related serious adverse events were reported in 26.1% of the patients with ganitumab and in 6.5% with placebo. Non-progression related fatal events were more common with ganitumab (5 versus 2 patients). The ganitumab group experienced more dose delays which resulted in lower relative dose intensity of chemotherapy in the experimental group. In an exploratory model IGFBP2 expression was predictive of ganitumab response (treatment interaction; PFS, P = 0.03; OS, P = 0.01). CONCLUSION: Addition of ganitumab to CP chemotherapy in primary EOC did not improve PFS. Our results do not support further study of ganitumab in unselected EOC patients.

Conservative surgery for ovarian torsion in young women: perioperative complications and national trends.

OBJECTIVE: To analyse populational trends and perioperative complications following conservative surgery versus oophorectomy in women <50 years of age with ovarian torsion. DESIGN: Population-based retrospective observational study. SETTING: Nationwide Inpatient Sample in the USA (2001-2015). POPULATION: In all, 89 177 ovarian torsions including 20 597 (23.1%) conservative surgeries and 68 580 (76.9%) oophorectomies. METHODS: (1) Trend analysis to assess utilisation of conservative surgery over time, (2) multivariable binary logistic regression to identify independent factors associated with conservative surgery and (3) inverse probability of treatment weighting with a generalised estimating equation to analyze perioperative complications. MAIN OUTCOME MEASURES: Trends, characteristics and complications related to conservative surgery. RESULTS: Performance of conservative surgery increased from 18.9 to 25.1% between 2001 and 2015 (32.8% relative increase, P = 0.001) but decreased steadily after age 15, and sharply declined after age 35 (P < 0.001). On multivariable analysis, younger age exhibited the largest effect size for conservative surgery among the independent factors (adjusted odds ratios 3.39-7.96, P < 0.001). In the weighted model, conservative surgery was associated with an approximately 30% decreased risk of perioperative complications overall (10.0% versus 13.6%, odds ratio 0.73, 95% confidence interval 0.62-0.85, P < 0.001) and was not associated with venous thromboembolism (0.2 versus 0.3%, P = 0.457) or sepsis (0.4 versus 0.3%, P = 0.638). CONCLUSION: There has been an increasing utilisation of conservative surgery for ovarian torsion in the USA in recent years. Our study suggests that conservative surgery for ovarian torsion may not be associated with increased perioperative complications. TWEETABLE ABSTRACT: Conservative surgery for ovarian torsion may not be associated with increased perioperative complications.

Significance of uterine corpus tumor invasion in early-stage cervical cancer.

OBJECTIVE: To examine characteristics and survival outcomes of women with surgically-treated cervical cancer exhibiting uterine corpus tumor invasion. METHODS: We utilized The Surveillance, Epidemiology, and End Results Program to identify cervical cancer patients who underwent hysterectomy between 1973 and 2003. Logistic regression models were used to identify risk factors for uterine corpus tumor invasion on multivariable analysis. Association of uterine corpus tumor invasion and cause-specific survival (CSS) from cervical cancer was examined with Cox proportional hazard regression models on multivariable analysis. RESULTS: We identified 837 (4.9%) cases of uterine corpus invasion and 16,237 (95.1%) cases of non-invasion. Median follow-up time was 14.0 years. There were 1642 deaths due to cervical cancer. Uterine corpus invasion was independently associated with older age, non-squamous histology, high-grade tumors, large tumor size, and nodal metastasis on multivariable analysis (all, P < 0.001). On univariable analysis, uterine corpus tumor invasion was significantly associated with decreased CSS compared to the non-invasion (5-year rates, 79.0% versus 94.5%, P < 0.001). After controlling for other significant prognostic factors, uterine corpus tumor invasion remained an independent prognostic factor for decreased CSS (adjusted-hazard ratio 1.45, 95% confidence interval 1.21-1.74). Among stage T1b cases (n = 6730), uterine corpus tumor invasion remained an independent prognostic factor for decreased CSS (adjusted-hazard ratio 1.95, 95%CI 1.47-2.60). Uterine corpus tumor invasion was significantly associated with decreased CSS in stage T1b1 disease (74.5% versus 90.7%, P < 0.001) and in stage T1b2 disease (67.0% versus 79.5%, P = 0.01). CONCLUSION: Uterine corpus tumor invasion is an independent prognostic factor for decreased survival of women with early-stage cervical cancer.

[OUTCOME OF PELVIC EXENTERATION FOR LOCALLY ADVANCED CANCER OF THE PELVIC ORGANS].

We analyzed the outcomes of pelvic exenteration in patients with locally advanced cancer of the pelvic organs. During the period from 2006 to 2013 at the Leningrad Regional Oncology Dispensary there were carried out 218 exenterations of the pelvis. Postoperative complications occurred in 68 patients (31.2%), 17 patients died, mortality was 7.8%. The average surgery time was 186 minutes. The average blood loss was 860 ml. In assessing the oncological effectiveness of surgical interventions it was revealed that a 5-year survival rate ranged from 32% in bladder cancer, up to 50% in cervical cancer. Careful selection of patients, multidisciplinary approach to the problem has paramount importance to achieve satisfactory outcomes.

[Results of surgical treatment of oral cavity cancer T1-2N0M0].

The article shows the results of treatment of 20 patients (aged from 46 to 85 years old) with early oral cavity squamous cell carcinoma at the period from April 2009 to January 2011. The surgery included the resection of primary tumor and neck dissection in all the patients. The primary tumor was removed by mouth access in 10 patients and combined method was used in 10 cases. The selective neck dissection was carried out in 22 cases. The oral cavity wounds were closed primarily by local flaps in 10 patients, some small residual defects were left open in 3 cases. The reconstructions with remote skin-muscular infrahyoid flap were performed in 7 patients. The free revascularized radial skin-fascia flap was used in 3 cases. A follow-up period was from 24 to 44 months. The primary local regional control consisted of 85% in given group of patients. The rate of recurrence of the second primary metachronous tumor was 15%. Tumors were located in the oral cavity. Overall 3-year survival was 90% (18 out of 20 patients).

[Immediate and long-term results of treatment after pelvic exenteration for locally advanced cervical cancer].

Results of treatment after pelvic exenterations were analyzed in 73 patients with locally advanced cervical cancer: 4 patients--Stage IIIB, 24--Stage IVA, 45--with local recurrences after combined (15) or radiation therapy (30) for the period from 2007 to 2012. The median age was 51 years (22 to 77). Variants of pelvic exenterations were as follows: 30 front, 6 rear supralevatory, 37 total (full monoblock removal of the pelvic organs above the pelvic diaphragm): 6 infralevatory and 31 supralevatory. Postoperative complications were recorded in 21 patients (28.8%), postoperative lethality--6.8%. Long-term results of treatment were observed among 34 patients operated in 2007-2009. One-year survival was 50.0%, two-year--47.1%, three-year--41.2%, four-year--38.2%, five-year--38.2%. Best results were observed in the group of primary patients (Stages IIIB, IVA) with only interorgan fistulas. Low survival rate was registered in the group of patients with recurrences after radiotherapy as intraoperatively, despite both data of CT and MRI and the results of express histological examination, it was impossible to assess accurately the lateral edge of the tumor growth.

[Microsurgical autografting for reconstruction of head and neck oncological defects. An analysis of 60 cases].

The authors analyzed results of the free flap transfer in surgery of head and neck. 60 operations were performed since October 2006 till May 2012. Indications for using them were reconstruction of the mucosa of the oral cavity and the pharynx in 48 cases, the extensive defects of skin and soft tissues of the head and neck in 12 cases. All cases except 2 had the initial reconstruction. First 18 operations were performed with the binocular loupes, followed by using operating microscope. During the operations 42 radial skin-fascia flaps, 10 anterolateral femoral flaps, 5 thoracodorsal flaps, 1 anteromedial femoral flap, 1 scapular skin bone flap and 1 jejunal flap were used. During the early postoperative period one of the patients died (postoperative lethality 1.7%). Necrosis of flaps took place in 6 cases (5 radial skin-fascia flaps, 1 thoracodorsal flap). The causes of failures were assessed as arterial thrombosis (1 case), venous thrombosis (2 cases), postoperative infection (1 case). The exact cause in 2 cases couldn't be determined. Thus, the total success in the given series of surgery was 88.9%.

[Pelvic exenteration in surgery for colorectal cancer].

A total of 1436 patients with colorectal cancer underwent resective surgery: 244 (15.6%) received combined interventions, 94 (41.9%) pelvic exenteration (PE), 38 (40.4%) complete PE, 9 (9.6%) of which were infralevator and 29 (30.8%) supralevator. In 56 (59.6%) patients posterior PE was performed, supralevator was performed in 17 (18.1%) cases and infralevator in 39 (41.5%) cases. In 47 (69.1%) of 68 supralevator PE recipients colonic anastomosis was formed. In 21 (38.9%) patients a terminal colostoma was formed, in 29 (76.3%) of 38 patients incontinent urinary diversion was formed. Continent urinary diversion was performed in 9 (23.7%) patients. Twenty six (27.6%) patients had 43 post-operative complications which were lethal in 7 (26.9%) cases.

[Use of vascularized free flaps for reconstruction of oncological defects in the head and neck].

The aim of the study is to assess our results with free flap transfer. Since October, 2005 till December, 2011 51 operations were performed. Mucosa of upper digestive tract was reconstructed in 40 cases, soft tissues and skin of the head and neck region-in 11 cases. Reconstruction was primary in all but 2 cases. 18 first cases were performed with 2,5x and 4x binocular loupes magnification. Operating microscope was used in another 33 cases. 37 radial forearm fasciocutaneous flaps, 5 latissimus dorsi musculocutaneous flaps, 7 anterolateral thigh flaps, 1 scapular osteocutaneous were used with the single case of visceral flap--jejunal free flap. Death in early postoperative period occurred once. Complete flap loss occurred six times. Five radial and one latissimus dorsi free flaps were lost. Arterial thrombosis is considered as a primary cause of failure in one case, venous thrombosis-in two cases. Severe postoperative infection was considered as a primary cause of failure in one case. In remaining 2 cases the cause of flap loss could not be determined exactly. There were three cases of revision surgery with attempts to reperform venous anastomosis, one of them was successful. Overall success rate in this series is 86,3 %. The main cause of such a low rate of success is a lack of experience.

[Characteristics of tumor growth in patients with locally-advanced gastric cancer].

Locally-advanced gastric cancer features predominance of prognostically unfavorable histological patterns (infiltrative growth--in 87.9%, tumor grades II-IV--69.5%). Tumor invasion into two adjacent organs or more frequently occurs in totally-involved stomach (65.2+/-9.7%), poorly-differentiated (grade Ill) tumors (44.9+/-4.5%) under-differentiated ones (grade IV) (45.9+/-8.2%). Invasion into one adjacent organ is significantly predominant (p

[Ways to improve the quality of life of elderly and senile patients after the operation by Brikker].

The present study is devoted to improving quality of life of patients in elderly and senile age after operation of Bricker by finding the optimal method of forming ureterointestinal anastomosis. From 2007 to 2009 103 patients of elderly and senile age with diseases requiring removal of the bladder were treated in the Lenigrad Regional Oncology Centre. All the patients were made cystectomy. Patients were divided into two groups: In 1st group, the ureterointestinal anastomosis was formed a classical way "end to side" described Bricker, in the 2nd group ureterointestinal anastomosis was performed by the method of Wallace - "common area". Pathological conditions developed in patients in late postoperative period were as follows: hydronephrosis in early and later stages, obstructive pyelonephritis, frequent attacks of chronic pyelonephritis, chronic renal failure, urinary fistula. Formation of ureterointestinal anastomosis by Wallace during surgery reduces the amount of later postoperative complications. Quality of life was better after the formation of ureterointestinal anastomosis by Wallace.

[Outcomes of surgical treatment for locally advanced gastric cancer].

Results of surgical treatment of 223 patients with locally advanced gastric cancer (2000-2005) are presented. Postoperative complications rate was 25.6 +/- 2.5%, mortality--5.8 +/- 0.7%, overall survival--17.9 +/- 2.6%, median survival--12 months. Survival rates were higher following palliative treatment. Groups of patients in which RO resections failed to improve the end results were identified. That in turn calls for working out differentiated surgical strategies.

[The use of myocutaneous flap for reconstruction of surgical defects in the oropharyngeal area].

Oncological Dispensary of Leningrad Region, St.Petersburg Our paper deals with evaluation of the results of using distal pectoralis major myocutaneous flap (38) in 37 patients; bilateral dissection of tissue--1. Plastic reconstruction of surgical effects of the oral cavity and pharynx was performed in 27 (skin cancer--8, parotid salivary gland tumor--1). Flap was used to both shield the parotid artery and prevent erosive bleeding following radical cervical dissection, urgent plastic surgery--30, postponed--8. Complication, chiefly slight was reported in 60.5% and treated conservatively. Total necrosis was identified in 2 (5.3%), partial--4 (10.8%), salivary fistula--10 out of 27 reconstructions of the upper intestinal tract (18.4%), cervical suture failure--7 (18.4%), flap avulsion from wound edges--6 (15.8%), wound edge avulsion--2 (5.3%). Nasogastric probe for feeding was used for approx. 23.7 days. Feeding per os after the first operation was restored in 23 (85.2%). Repeat reconstruction using pectoralis major myocutaneous flap has proved effective in patients with surgical effects of head and neck.

[Quality of life of patients with breast cancer receiving hormonal therapy, depending on age and marital status].

Our study involved 247 patients with histologically verified breast tumors, aged 48-89, who had received hormones - tamoxifen as first-line therapy, exemestan (second-line) for 12 months. FACT-B and FACT-G questionnaires were used to assess quality of life. Worse results were reported in tamoxifen-treated patients older than 60 years. Indices of emotional and social security in the two groups: 60-70 year-olds (10.8+/-0.96% and 14.3+/-1.27% vis-à-vis 14.8+/-1.31% and 15.6+/-1.42%, respectively) and over 70 year-olds (15.2+/-1.46% and 15.8+/-1.48%, respectively). Our evidence suggested that a large-seale complex of effective psychological rehabilitation be given, particularly, to those under 60, married andlor with minors, right from the very beginning of treatment.

[Palliative resection in esophageal cancer].

A 20-year experience of treatment of 633 patients with cancer of the thoracic esophagus has been evaluated. Far advanced disease was diagnosed in 384 (60.7%). Radical, palliative and symptomatic surgery was performed in 421 (66.5%), 44. (6.9%) and 168 (26.6%), respectively. No significant differences were reported between the immediate results of radical and palliative treatment. Since survival and quality of life after palliative resection appeared to be better than after symptomatic surgery, the former should be recommended for use in clinic.

A phase II study of Hsp-7 (SGN-00101) in women with high-grade cervical intraepithelial neoplasia.

OBJECTIVE: Approximately 2 million women worldwide are infected with high-risk human papillomaviruses (HPV), resulting in a substantial risk for the development of invasive lower genital malignancies. This study was undertaken to determine the effects of vaccination with a protein encoding a bacterial heat shock protein fused to sequences from the oncogenic E7 protein of HPV-16 in women with high-grade cervical intraepithelial neoplasia. Endpoints included lesion regression, immune response, and viral clearance. METHODS: Twenty-one women were prospectively entered into an IRB-approved Phase II study. All women had biopsy-proven high-grade cervical intraepithelial neoplasia and persistent post-biopsy lesions visible by colposcopy. Four injections of HPV-16 Hsp E7 fusion protein at a dose of 500 mug were given 3 weeks apart after which Loop Electrosurgical Excision of the Transformation Zone (LLETZ) was performed. Immune parameters were evaluated pre-vaccine and at the time of LLETZ, and HPV testing was performed at intervals before and after LLETZ. Study subjects were followed for 1 year after LLETZ. RESULTS: Seven of 20 women (35%) evaluable for response had complete regression of their intraepithelial neoplasia at the time of LLETZ, 1 (5%) had regression to CIN I, 11 (55%) had stable disease and 1 (5%) had progression due to enlargement of her lesion. Immune responses were seen in 9 of the 17 women tested; 5 of the 7 complete responders had an immune response. Only 5 of 21 women had HPV-16 or -18. HPV clearance was not associated with lesion regression. CONCLUSION: Hsp-7 (SGN-00101), at this dose and schedule induced lesion regression in women with high-grade intraepithelial neoplasia. The fact that regression was correlated with immune response suggests that enhancing the immunogenicity of this vaccine may lead to improvement in the rate of lesion eradication.

Endometrial cancer patients have a significant risk of harboring isolated tumor cells in histologically negative lymph nodes.

In this study, we examine the prevalence of finding isolated tumor cells (ITCs) in negative lymph nodes of endometrial cancer patients using immunohistochemistry. Seventy-six endometrial cancer patients with lymph nodes histologically negative for metastatic disease were examined. Nodal tissue sections were stained with anticytokeratin antibodies AE-1 and CAM 5.2. Nodes with single or groups of cells (two to four cells) < or =0.2 mm and showing cytokeratin reactivity were positive for ITCs. Findings were compared to features of the primary tumor and patient outcome. ITCs were present in 31 of 1712 lymph nodes. Fifteen (19.7%) patients had ITC-positive nodes. ITCs involved only pelvic nodes in nine cases, only para-aortic nodes in five cases, and pelvic and para-aortic in one case. Tumor in adnexa was the only pathologic feature associated with nodal ITCs (P= 0.0485). All 15 patients with nodal ITCs were alive at follow-up. One (6.7%) patient suffered recurrent disease but was alive at last encounter. Disease recurred in 5 (8.8%) of 57 patients without nodal ITCs. Two are alive without disease, two alive with disease, and one died from her cancer. In summary, a significant proportion of endometrial cancer patients have ITCs detected by immunohistochemistry in histologically negative regional lymph nodes.

The impact of anti HPV vaccination on cervical cancer incidence and HPV induced cervical lesions: consequences for clinical management.

Cervical cancer is the second most common cause of cancer-related deaths in women worldwide. Screening for cervical cancer is accomplished utilizing a Pap smear and pelvic exam. While this technology is widely available and has reduced cervical cancer incidence in industrialized nations, it is not readily available in third world countries in which cervical cancer incidence and mortality is high. Development of cervical cancer is associated with infection with high risk types of human papillomavirus (HPV) creating a unique opportunity to prevent or treat cervical cancer through anti-viral vaccination strategies. Several strategies have been examined in clinical trials for both the prevention of HPV infection and the treatment of pre-existing HPV-related disease. Clinical trials utilizing prophylactic vaccines containing virus-like particles (VLPs) indicate good vaccine efficacy and it is predicted that a prophylactic vaccine may be available within the next five years. But, preclinical research in this area continues in order to deal with issues such as cost of vaccination in underserved third world populations. A majority of clinical trials using therapeutic agents which aim to prevent the progression of pre-existing HPV associated lesions or cancers have shown limited efficacy in eradicating established tumors in humans possibly due to examining patients with more advanced-stage cancer who tend to have decreased immune function. Future trends in clinical trials with therapeutic agents will examine patients with early stage cancers or pre-invasive lesions in order to prevent invasive cervical cancer. Meanwhile, preclinical studies in this field continue and include the further exploration of peptide or protein vaccination, and the delivery of HPV antigens in DNA-based vaccines or in viral vectors. Given that cervical cancers are caused by the human papillomavirus, the prospect of therapeutic vaccination to treat existing lesions and prophylactic vaccination to prevent persistent infection with the virus are high and may be implemented in the near future. The consequences for clinical management may include a significant reduction in the frequency of Pap smear screening in the case of prophylactic vaccines, and the availability of less invasive and disfiguring treatment options for women with pre-existing HPV associated lesions in the case of therapeutic vaccines. Implementation of both prophylactic and therapeutic vaccine regimens could result in a significant reduction of health care costs and reduction of worldwide cervical cancer incidence.