Improved surgical safety after laparoscopic compared to open surgery for apparent early stage endometrial cancer: results from a randomised controlled trial

AimTo compare Total Laparoscopic Hysterectomy (TLH) and Total Abdominal Hysterectomy (TAH) with regard to surgical safety.MethodsBetween October 2005 and June 2010, 760 patients with apparent early stage endometrial cancer were enroled in a multicentre, randomised clinical trial (LACE) comparing outcomes following TLH or TAH. The main study end points for this analysis were surgical adverse events (AE), hospital length of stay, conversion from laparoscopy to laparotomy, including 753 patients who completed at least 6 weeks of follow-up. Postoperative AEs were graded according to Common Toxicity Criteria (V3), and those immediately life-threatening, requiring inpatient hospitalisation or prolonged hospitalisation, or resulting in persistent or significant disability/incapacity were regarded as serious AEs.ResultsThe incidence of intra-operative AEs was comparable in either group. The incidence of post-operative AE CTC grade 3+ (18.6% in TAH, 12.9% in TLH, p 0.03) and serious AE (14.3% in TAH, 8.2% in TLH, p 0.007) was significantly higher in the TAH group compared to the TLH group. Mean operating time was 132 and 107 min, and median length of hospital stay was 2 and 5 days in the TLH and TAH group, respectively (p < 0.0001). The decline of haemoglobin from baseline to day 1 postoperatively was 2 g/L less in the TLH group (p 0.006).ConclusionsCompared to TAH, TLH is associated with a significantly decreased risk of major surgical AEs. A laparoscopic surgical approach to early stage endometrial cancer is safe.     

Therapeutic role of systematic retroperitoneal lymphadenectomy in endometrial cancer

ObjectiveThe purpose of this study was to evaluate the therapeutic role of systematic retroperitoneal lymphadenectomy in patients with endometrial cancer.MethodsFrom December 2003 to December 2008, 349 eligible patients who underwent surgical staging procedures at primary treatment were retrospectively analyzed: systematic lymphadenectomy group (n = 246) and no-lymphadenectomy group (n = 103). Survival was analyzed using Kaplan-Meier method and Cox proportional hazards model.ResultsOverall, patients who underwent lymphadenectomy improved 5-year disease-free survival (89.0% versus 80.7%, P = 0.019) and overall survival (92.8% versus 81.5%, P = 0.001) compared to those who did not undergo lymphadenectomy. Overall survival was not related to lymphadenectomy in 212 low-risk patients (93.1% versus 84.6%, P = 0.176). However, this association was found in 137 patients with intermediate and high-risk (86.2% versus 73.3%, P = 0.021). Multivariate Cox regression analysis showed that FIGO stage (P = 0.037) and lymphadenectomy (P = 0.023) were independent prognostic factors for overall survival.ConclusionsSystematic retroperitoneal lymphadenectomy has a potentially therapeutic role on survival in surgically staged patients with endometrial cancer.     

Preliminary results of consolidation chemotherapy following concurrent chemoradiation after radical surgery in high-risk early-stage carcinoma of the uterine cervix

AimsTo evaluate the efficacy and toxicity of consolidation chemotherapy after concurrent chemoradiation (CCRT) with 5-fluorouracil (5-FU) and cisplatin in the treatment of high-risk, early stage cervical carcinoma after radical surgery.Materials and methodsWomen with clinical stage IB and IIA cervical carcinoma, initially treated with radical hysterectomy and pelvic lymphadenectomy, and who had positive pelvic lymph nodes, positive margins, parametrial involvement, or all three, were divided into either a CCRT alone group or a consolidation chemotherapy after CCRT group. Three cycles of chemotherapy were given to the CCRT alone group, and six cycles to the consolidation chemotherapy group. Women in each group received 50.4 Gy external radiation in 28 fractions to a standard pelvic field. Chemotherapy consisted of cisplatin 60 mg/m² (× 1) and 5-FU 1000 mg/m²/d (× 5) every 3 weeks, with the first and second cycles given concurrent with radiation. Survival and toxicity were compared between the two groups.ResultsForty women were evaluable (25 in the CCRT alone group and 15 in the consolidation chemotherapy group). The estimated 2-year progression-free survival was 87.7% in the CCRT alone group and 67.0% in the consolidation chemotherapy group. The estimated 2-year overall survival was 95.8% in the CCRT alone group and 100% in the consolidation chemotherapy group. However, no significant differences were found in progression-free and overall survival in the two groups (P = 0.17 and P = 0.29, respectively). Grade 2 or higher leukopenia and neutropenia were significantly more frequent in the consolidation chemotherapy group than in the CCRT alone group (P = 0.02 and P < 0.01, respectively).ConclusionsAlthough the sample size was small, and this study was not randomised, these results suggest that consolidation chemotherapy may not improve survival. Rather, it may increase haematologic toxicities for women with high-risk, early stage cervical carcinoma who undergo radical surgery followed by CCRT.     

Safety of bevacizumab in metastatic breast cancer patients undergoing surgery

BackgroundEvaluate the safety of surgery in relation to bevacizumab in the first-line treatment of metastatic breast cancer (mBC) in two international trials.Patients and methodsThe incidence, type and timing of post-surgical bleeding events and wound-healing complications were assessed in surgical patients in the AVastin And DOcetaxel (AVADO) (NCT00333775) and Avastin THErapy for advaNced breAst cancer (ATHENA) (NCT00448591) trials. Both study protocols followed recommendations to withhold bevacizumab for at least 6 weeks before elective surgery and to wait 28 days (or until the wound was fully healed) after major surgery before recommencing bevacizumab therapy.ResultsIn AVADO, 221 surgical procedures (55 major, 166 minor) were performed in 155 patients. In ATHENA, 1190 surgical procedures (435 major, 755 minor) were performed in 672 patients. One bevacizumab-treated AVADO patient (0.9%) who underwent surgery experienced a grade 3 bleeding event. In ATHENA, six patients (0.9%) who underwent surgery experienced grade 3 bleeding events and one patient (0.1%) experienced a grade 4 bleeding event. No grade 5 bleeding events in patients undergoing surgery were reported in either study. One grade 3 wound-healing complication was reported in each of the AVADO arms: placebo (n = 46, 2.2%), bevacizumab 7.5 mg/kg (n = 57, 1.8%) and bevacizumab 15 mg/kg (n = 52, 1.9%). Incidence of grade 3–4 wound-healing complications in ATHENA was 2.2% and 1.3% in patients undergoing minor or major surgery, respectively.ConclusionsSurgery can be performed on patients with mBC undergoing bevacizumab therapy with a low risk of severe bleeding or wound-healing complications post surgery, if current labelling recommendations are adhered to.     

Integral Dose in Three-dimensional Conformal Radiotherapy, Intensity-modulated Radiotherapy and Helical Tomotherapy

AimsTo evaluate the integral dose to organs at risk (OARs), normal tissue and the whole body in three-dimensional conformal radiotherapy (3DCRT), intensity-modulated radiotherapy (IMRT) and helical tomotherapy for whole pelvic radiotherapy (WPRT) in postoperative endometrial cancer patients.Materials and methodsWe selected 10 patients with endometrial cancer undergoing postoperative WPRT. Plans of 6MV-3DCRT, 18MV-3DCRT, 6MV-IMRT, 18MV-IMRT and helical tomotherapy were developed for each patient. The integral doses to OARs, normal tissue and the whole body were compared.ResultsCompared with 3DCRT, both IMRT and helical tomotherapy significantly improved dose conformity and the integral doses to OARs (8.8–29.9%, P < 0.05). Compared with 6MV-3DCRT, IMRT resulted in 13.2 and 11.0% lower integral doses to normal tissue and the whole body, respectively (P = 0.00), whereas no significant difference was found with helical tomotherapy. Compared directly with IMRT, helical tomotherapy reduced the integral doses to the rectum and bladder. However, the integral doses to normal tissue were 13.9 and 17.1% higher than 6MV-IMRT and 18MV-IMRT plans, respectively (P = 0.00); the integral doses to pelvic bones also slightly increased with helical tomotherapy. The use of 18MV resulted in 5.8 and 2.7% lower integral doses to normal tissue and 4.8 and 2.1% lower integral doses to the whole body in the 3DCRT and IMRT plans, respectively (P = 0.00).ConclusionsResults show that IMRT and helical tomotherapy offer better conformity and lower integral doses to OARs for postoperative WPRT of endometrial cancers compared with 3DCRT. The integral doses to normal tissue and the whole body were significantly lower with IMRT, whereas no significant difference was found with helical tomotherapy compared with 6MV-3DCRT. Compared directly with IMRT, helical tomotherapy further reduced the integral doses to the rectum and bladder, at the expense of a slightly higher integral dose to pelvic bones and normal tissue. The use of 18MV improved the integral doses to normal tissue and the whole body in both 3DCRT and IMRT.     

Do Serum Levels of Eosinophil Granule-derived Protein Change in Patients Undergoing Pelvic Radiotherapy?

AimsEosinophils have an important role in the pathogenesis of inflammatory bowel disease, with faecal levels of the eosinophil granule proteins, eosinophil cationic protein (ECP) and eosinophil protein X (EPX) reflecting disease activity. Eosinophil crypt abscesses are a characteristic histological finding in acute gastrointestinal radiation-induced mucosal damage. This pilot study aimed to investigate changes in serum levels of ECP/EPX during pelvic radiotherapy.Materials and methodsPatients with no history of inflammatory bowel disease, starting a 5-week course of pelvic radiotherapy, had serum ECP/EPX levels measured before radiotherapy and during the fourth week of treatment. Bowel toxicity was graded at week 4 using the Common Toxicity Criteria Scale.ResultsFifteen patients who were to undergo adjuvant radiotherapy for gynaecological cancer were recruited. The mean serum levels of ECP and EPX before treatment were 17.3 μg/l (range 2.0–49.3 μg/l) and 37.3 μg/l (range 12.0–94.0 μg/l), respectively. The mean serum levels during week 4 of radiotherapy for ECP and EPX were 43.0 μg/l (range 2.4–164.0 μg/l) and 38.7 μg/l (range 9.0–79.0 μg/l), respectively. Serum ECP levels increased at week 4 compared with levels before radiotherapy (P = 0.02). Acute bowel toxicity was seen in 12 patients (80%) at week 4: Grade 1 in 25% patients and Grade 2 in 75%. In this small study, no correlation was seen between acute bowel toxicity at week 4 and serum ECP or EPX levels.ConclusionsSerum ECP levels increase in response to pelvic irradiation. This may reflect the known involvement of eosinophils in the acute response to radiotherapy. Further study is required to determine when levels start to rise and their relationship to the degree of acute bowel toxicity.     

Five-year quality of life of endometrial cancer patients treated in the randomised Post Operative Radiation Therapy in Endometrial Cancer (PORTEC-2) trial and comparison with norm data

BackgroundThe PORTEC-2 trial showed efficacy and reduced side-effects of vaginal brachytherapy (VBT) compared with external beam pelvic radiotherapy (EBRT) for patients with high-intermediate risk endometrial cancer. The current analysis was done to evaluate long-term health related quality of life (HRQL), and compare HRQL of patients to an age-matched norm population.MethodsPatients were randomly allocated to EBRT (n = 214) or VBT (n = 213). HRQL was assessed using EORTC QLQ-C30 and subscales from PR25 and OV28 (bladder, bowel, sexual symptoms); and compared to norm data.FindingsMedian follow-up was 65 months; 348 (81%) patients were evaluable for HRQL (EBRT n = 166, VBT n = 182). At baseline, patient functioning was at lowest level, increasing during and after radiotherapy to reach a plateau after 12 months, within range of scores of the norm population. VBT patients reported better social functioning (p = 0.005) and lower symptom scores for diarrhoea, faecal leakage, need to stay close to a toilet and limitation in daily activities due to bowel symptoms (p ⩽ 0.001), compared to EBRT. There were no differences in sexual functioning or symptoms between the treatment groups; however, sexual functioning was lower and sexual symptoms more frequent in both treatment groups compared to the norm population.InterpretationPatients who received EBRT reported clinically relevant higher levels of bowel symptoms and related limitations in daily activities with lower social functioning, 5 years after treatment. VBT provides a better HRQL, which remained similar to that of an age-matched norm population, except for sexual symptoms which were more frequent in both treatment groups.     

Radiation dose escalation using intensity modulated radiation therapy for gross unresected node-positive endometrial cancer

PurposeTo determine rates of nodal control and survival in patients with endometrial cancer treated with intensity modulated radiation therapy (IMRT) with dose escalation to unresected nodal disease.Methods and MaterialsBetween November 2005 and April 2011, 22 endometrial-cancer patients received IMRT with dose escalation to gross nodal disease with curative intent. Twelve were treated for recurrent disease (RD) and 10 in the primary setting, of whom 5 had a hysterectomy. The boost area included pelvic nodes in 9 patients (41%), paraaortic nodes (PAN) in 6 (27%) and both pelvic and PAN in 7 (32%). The median gross nodal dose was 63 Gy (range, 55-65). Rates of local control, disease-free survival (DFS) and overall survival (OS) were determined using the Kaplan-Meier method.ResultsMedian follow-up time was 37.6 months (range, 10-88). Median nodal size was 2.25 cm (range, 1-6.9). The median time to first relapse after IMRT was 12 months (range, 6-49). Relapses occurred in 5/12 RD (42%), 1/5 hysterectomy (20%), and 5/5 inoperable cases. Nodal relapses occurred in-field in 3/12 RD and 1/5 hysterectomy patients. At 3 years, nodal control was 86%, DFS was 58% and OS was 68%. Three patients experienced grade 3 late hematologic toxicity (anemia). No late grade ≥ 3 gastrointestinal or genitourinary toxicity occurred.ConclusionsIn endometrial cancer, the use of IMRT for dose escalation to gross nodal disease is feasible with acceptable rates of toxicity. Patients with nodal recurrence or unresectable nodal disease after a hysterectomy may benefit from radiation dose escalation.     

The role of postoperative radiation therapy for endometrial cancer: Executive Summary of an American Society for Radiation Oncology evidence-based guideline

PurposeTo present evidence-based guidelines for adjuvant radiation in the treatment of endometrial cancer.Methods and materialsKey clinical questions to be addressed in this evidence-based guideline on endometrial cancer were identified. A comprehensive literature review was performed to identify studies that included no adjuvant therapy, or pelvic radiation or vaginal brachytherapy with or without systemic chemotherapy. Outcomes included local control, survival rates, and overall assessment of quality of life.ResultsPatients with grade 1 or 2 cancers with either no invasion or < 50% myometrial invasion (MI), especially when no other high risk features are present, can be safely observed after hysterectomy. Vaginal cuff brachytherapy is as effective as pelvic radiation therapy at preventing vaginal recurrence for patients with grade 1 or 2 cancers with ≥ 50% MI or grade 3 tumors with < 50% MI. Patients with grade 3 cancer with ≥ 50% MI or cervical stroma invasion may benefit from pelvic radiation to reduce the risk of pelvic recurrence. There is limited evidence for a benefit to vaginal cuff brachytherapy following pelvic radiation. Multimodality treatment is recommended for patients with positive nodes or involved uterine serosa, ovaries or fallopian tubes, vagina, bladder, or rectum.ConclusionsExternal beam and vaginal brachytherapy remain integral aspects of adjuvant therapy for endometrial cancer.     

Results of external-beam radiotherapy alone in invasive cancer of the uterine cervix: a retrospective analysis

AimsIn this retrospective audit, we describe the results of external-beam radiotherapy (EBRT) alone in patients with invasive cancer of the cervix treated at our centre.Material and MethodsWe included 146 patients with invasive cancer of the cervix who were treated with EBRT to a total dose of 60–66 Gy between January 1996 and December 2001. None of these patients were suitable for intracavitary radiotherapy (ICRT) after a median dose of 46 Gy. A boost dose of 14–20 Gy was given after a gap of 2–4 weeks. Most patients belonged to stage IIIB (n = 124).ResultsFollow-up of patients at risk ranged from 19 to 89 months (median 48 months). One hundred and thirty-six patients (93.2%) received EBRT to a dose of 66 Gy, and 10 patients (6.8%) received 60 Gy. Overall treatment time (OTT) ranged from 56 to 160 days (median 78 days). At completion of 46 Gy of EBRT, 63 patients achieved partial response and 83 patients had stable disease. Five-year overall survival, disease-free survival (DFS) and pelvic control were 15.1% (median 9 months), 11.6% (median 5 months) and 21.9% (median 6 months), respectively. Factors found to affect 5-year pelvic control in univariate analysis by Kaplan–Meier method were response to EBRT at 46 Gy (partial response 36.5% and stable disease 10.8%), age (≥50 years 28.8% and <50 years 13.6%) and OTT (<90 days 26.5% and ≥90 days 12.5%). For DFS and overall survival, response to EBRT was the only factor that was significant in univariate analysis. In multivariate analysis by Cox's proportional hazard model, response to EBRT was the only factor to influence pelvic control (P = 0.007), DFS (P = 0.01) and overall survival (P < 0.001).ConclusionsOverall outcome of patients in whom ICRT was not given remains less than satisfactory. Response to EBRT emerged as the most important factor to predict all clinical outcomes. To improve upon the dismal results of EBRT alone, we will have to decrease the OTT and consider concurrent chemo-radiation with cisplatin.     

Acute and Late Toxicity in Radical Radiotherapy for Bladder Cancer

AimsTo evaluate the incidence, severity and kinetics of acute and late toxicity from bladder and bowels in patients with bladder cancer treated with radical radiotherapy.Materials and methodsThe retrospective analysis was based on 487 patients with T2, T3 bladder cancer, treated with radiotherapy between 1975 and 1995. The pelvis was irradiated electively in 303 patients; in the remaining patients, the bladder alone was treated. The mean total radiation dose to the bladder was 65.5 Gy. Various schedules of protracted, conventional and accelerated radiotherapy were used. The influence of selected factors on maximum acute toxicity and late toxicity was assessed. The kinetics of acute toxicity was also evaluated. The median follow-up was 76 months.ResultsSeven patients did not complete treatment due to excessive acute toxicity. The incidence of grade ≥3 acute bladder and bowel toxicity was 5 and 3%, respectively. The actuarial, 5-year incidence of grade ≥3 late bladder and bowel toxicity was 12 and 3%, respectively. The most important factors influencing acute toxicity were: T-stage (P = 0.004) for the bladder and pelvic irradiation (P = 0.044) and dose intensity (P = 0.000) for the bowels. The latency of both early bladder and bowel toxicity was correlated with dose intensity. The most important factor influencing late bladder toxicity was acute toxicity score (P = 0.000). Late bowel toxicity was also influenced by acute bowel toxicity (P = 0.04).ConclusionsThe severity of acute bowel toxicity is related to pelvic irradiation and dose intensity. The severity of acute bladder toxicity depends on T-stage. The increase in dose intensity is associated with shorter latency to maximum acute bladder and bowel toxicity. The severity of acute bladder and bowel toxicity influences the risk of late effects from those organs.     

Is There a Role for Adjuvant Hysterectomy after Suboptimal Concurrent Chemoradiation in Cervical Carcinoma?

AimsFailure to carry out intracavitary brachytherapy (ICBT) in cervical carcinoma results in suboptimal chemoradiation and increases the risk of recurrence. The aim of this study was to investigate the role of adjuvant hysterectomy after unsuccessful ICBT.Materials and methodsA retrospective analysis was carried out of all women referred with cervical carcinoma between January 1999 and July 2007 where ICBT insertion was unsuccessful after the initial chemoradiation. The data collected and analysed included histology, stage of disease, causes for unsuccessful ICBT insertion, the response to the initial chemoradiation, subsequent treatment, morbidity, recurrence rates and survival rates. Kaplan–Meier and Log-rank methods were used to analyse recurrence-free and overall survival rates.ResultsICBT insertion was unsuccessful in 19 of 208 (9%) patients. The causes of failure were: inability to dilate the cervix; uterine perforation; vesicovaginal fistula; patient refusal; other problems, including the presence of pyometrium, patient not fit for general anaesthetic, and narrow vagina; and consultant choice with no obvious reason. Fourteen of 19 patients (74%) received further pelvic external beam radiotherapy (EBRT) alone; five (26%) patients underwent adjuvant hysterectomy. The median follow-up for all patients was 63 months; 60 months for patients treated with adjuvant hysterectomy (range 31–68 months) and 85 months for patients treated with further EBRT. None of the patients treated with adjuvant hysterectomy developed any significant late toxicity. Seven patients (50%) treated with EBRT have relapsed compared with none in the adjuvant hysterectomy arm (P = 0.068). Six patients (43%) in the EBRT arm have subsequently died of recurrent disease compared with none in the adjuvant hysterectomy arm (P = 0.152).ConclusionsAdjuvant hysterectomy after unsuccessful ICBT does not seem to increase late toxicity and reduces the risk of pelvic recurrence and may improve survival. The role of adjuvant hysterectomy after suboptimal chemoradiation merits further investigation in clinical trials.     

Interstitial low dose rate brachytherapy for prostate cancer--a focus on intermediate- and high-risk disease

AimsTo investigate the role of brachytherapy in intermediate- and high-risk prostate cancer. We report our results and a review of published studies.Materials and methodsBetween March 1999 and April 2003, 300 patients were treated with low dose rate I-125 interstitial prostate brachytherapy and followed prospectively. The patients were stratified into low-, intermediate- and high-risk groups and received brachytherapy alone or in combination with external beam radiotherapy (EBRT) and/or neoadjuvant androgen deprivation (NAAD). One hundred and forty-six patients were classified as low risk, 111 as intermediate risk and 43 as high risk. Biochemical freedom from disease and prostate-specific antigen (PSA) nadirs were analysed for risk groups and for treatment received in each risk group.ResultsThe median follow-up was 45 months (range 33–82 months) with a mean age of 63 years. Actuarial 5-year biochemical relapse-free survival for the low-risk group was 96%, 89% for the intermediate-risk group and 93% for the high-risk group. When stratified by treatment group, low-risk patients had a 5-year actuarial biochemical relapse-free survival of 94% for brachytherapy alone (n = 77), 92% for NAAD and brachytherapy (n = 66) and 100% for NAAD, EBRT and brachytherapy (n = 3). In the intermediate-risk patients, biochemical relapse-free survival was 93% for brachytherapy alone (n = 15), 94% for NAAD and brachytherapy (n = 67), 75% for EBRT and brachytherapy (n = 4) and 92% for NAAD, EBRT and brachytherapy (n = 25). In the high-risk group, biochemical relapse-free survival was 100% for brachytherapy alone (n = 2), 88% for NAAD and brachytherapy (n = 7), 80% for EBRT and brachytherapy (n = 5) and 96% for NAAD, EBRT and brachytherapy (n = 29). Overall 3- and 4-year PSA = 0.5 ng/ml were achieved by 71 and 86%, respectively, and a 4-year PSA = 0.2 ng/ml was achieved by 63%.ConclusionAlthough the role of combination treatment with pelvic EBRT and androgen therapy is not clear, our early results show that many patients with intermediate- and high-risk disease have excellent results with brachytherapy.     

Local therapy is critical in localised pelvic rhabdomyosarcoma: experience of the International Society of Pediatric Oncology Malignant Mesenchymal Tumor (SIOP-MMT) committee

BackgroundLocalised pelvic rhabdomyosarcomas (pRMS) are rare tumours with a poorer prognosis than the majority of RMS. This study analysed patient outcome according to the type of local therapy delivered and the effect of disease-related factors on prognosis.Patients and methods97 children with localised pRMS were enrolled in the SIOP-MMT84, 89 and 95 studies. After primary surgery or biopsy, all children received ifosfamide/actinomycin/vincristine-based chemotherapy. Radiotherapy and surgery were planned in patients failing to achieve complete remission.ResultsMedian age at diagnosis was 52 months [5 months–18 years]. IRS staging was I for five patients, II for 15 and III for 77. Patients had embryonal RMS (N = 41), alveolar RMS (N = 29), botryoid RMS (N = 3), or not otherwise specified RMS (N = 24).Outcome87 patients achieved local control (90%), 37 relapsed (43%), mainly locally (84%). With a median follow-up of more than 10 years [4–22 years], 5-year OS was 66% (95% CI: 56–75%) and EFS was 52% (95% CI: 42–61%). Among the 18 IRS-I/II patients treated without radiotherapy, 15 survived. Seven out of the 20 IRS-III patients treated without local therapy died. In multivariate analysis, IRS staging, age greater than 10 years and lymph node involvement had a negative impact on OS. Perineal/perianal locations had a trend towards a worse prognosis.ConclusionpRMS still have a relatively poor prognosis. Radiotherapy or brachytherapy is necessary for all IRS-III patients including those with radiological complete remission after neoadjuvant chemotherapy with or without surgery. Radiotherapy may be withheld in IRS-I patients and children under 3 years with IRS-II pRMS.     

Age and bromodeoxyuridine labelling index as prognostic factors in high-grade gliomas treated with surgery and radiotherapy

AimsTo determine the prognostic value of proliferative potential and DNA ploidy in 72 brain tumours (36 grade III and 36 grade IV astrocytomas) using bromodeoxyuridine (BrdUrd) incorporation and flow cytometry.Material and methodsAll 72 patients underwent excision, mostly incomplete of the tumour. After surgery, eight patients received conventionally fractionated radiotherapy, 11 patients received accelerated radiotherapy, and 53 patients received hypofractionated radiotherapy. Tumour samples taken during surgery from each patient were incubated in vitro for 1 h at 37°C with BrdUrd using the high pressure oxygen method. The percentage of BrdUrd-labelled cells (BrdUrd labelling index [BrdUrd LI]), and the total DNA content were evaluated.ResultsThe tumours showed variability in the BrdUrd LI values, which ranged from 0.3 to 19.1%. No difference was observed in mean BrdUrd LI between grade III and grade IV sub-groups. A significantly higher percentage of DNA aneuploidy was observed in grade III gliomas (69.4%) than in grade IV gliomas (52.8%). Univariate analysis showed that younger patients (≤51 years) (P = 0.021) with grade III gliomas (P = 0.030) and low tumour proliferation rate (BrdUrd LI ≤ 2.7%, P = 0.028) had significantly higher 5-year survival rates. Tumour ploidy had no influence on patients' survival (P = 0.591). However, Cox multi-variate analysis showed that only age over 51 years, and high tumour proliferation rate (BrdUrd LI > 2.7%), were significant unfavourable prognostic factors in patient survival.ConclusionIn this study, independent prognostic factors for patients with high-grade gliomas treated with surgery and post-operative radiotherapy are age and tumour proliferation rate assessed according to the BrdUrd LI.     

Evaluating the efficacy of statins and ACE-inhibitors in reducing gastrointestinal toxicity in patients receiving radiotherapy for pelvic malignancies

Introduction3-Hydroxy-methylglutaryl coenzyme-A reductase inhibitors (statins) improve survival following pelvic irradiation for cancer. Large studies suggest that patients with hypertension may have reduced gastrointestinal (GI) toxicity. Animal data suggest that statins and ACE inhibitors (ACEi) may protect against normal tissue injury. Their efficacy in humans has not been reported.Aims/methodsTo evaluate the impact of statins and ACEi on normal tissue toxicity during radical pelvic radiotherapy. GI symptomatology was recorded prospectively before radiotherapy, weekly during treatment and 1 year later using the Inflammatory Bowel Disease Questionnaire – Bowel (IBDQ-B) subset. Cumulative acute toxicity (IBDQ-B AUC) and worst score were determined. Dose, brand and duration of statin and/or ACEi usage were obtained from General Practitioners.ResultsOf 308 patients recruited, 237 had evaluable acute drug and toxicity data and 164 had data at 1 year. Acutely, 38 patients (16%) were taking statins, 39 patients (16.5%) were taking ACEi and 18 patients (7.6%) were taking statin + ACEi. Mean changes in acute scores were 7.3 points (non-statin users), 7.3 (non-ACEi users) and 7.0 (non-statin + ACEi users) compared to 4.8 points (statin users), 5.0 points (ACEi users) and 4.9 points (statin + ACEi users). Statin use (p = 0.04) and combined statin + ACEi use (p = 0.008) were associated with reduced acute IBDQ-B AUC after controlling for baseline scores (ANOVA). At 1 year, users maintained higher IBDQ-B scores than non-users in all user subgroups.ConclusionUse of statin or statin + ACEi medication during radical pelvic radiotherapy significantly reduces acute gastrointestinal symptoms scores and also appears to provide longer-term sustained protection.     

Serum levels of selenium in patients with brain metastases from non-small cell lung cancer before and after radiotherapy

PurposeThis study was to evaluate the influence of radiotherapy on the selenium serum levels of non-small cell cancer patients with brain metastases.Patients and methodsThis prospective study included 95 non-small cell cancer patients with brain metastases treated by radiotherapy from December 2007 until November 2010. Plasma selenium levels were determined before and at the end of the radiotherapy. Age, body mass index (BMI), prior chemotherapy, pathological type and personal habits (smoking and alcoholism) were recorded for each patient.ResultsThe mean age was 63 years; the mean BMI was 27.6. Seventy-six patients (80%) were non-smokers. Sixty-two patients (65.3%) showed no drinking habits and 8 (8.4%) have no prior chemotherapy. Thirty-nine patients (41.1%) were adenocarcinoma, 51 (53.7%) were squamous cell carcinoma and five (5.3%) were large cell carcinoma. At the beginning of radiotherapy, the mean selenium level for all patients was 90.4 μg/l and after radiation this value dropped to56.3 μg/l. Multivariate analysis showed statistically significant difference in the plasma selenium concentration before and after radiotherapy for age (P < 0.001), BMI (P < 0.001), smoking (P < 0.001), alcoholism (P < 0.001), prior chemotherapy (P < 0.001) and pathological type (P < 0.001).ConclusionSignificant reduction in plasma levels of selenium was recorded in patients undergoing radiotherapy, suggesting attention to the nutritional status of this micronutrient and other antioxidant agents.     

Three-day treatment with imipenem for unexplained fever during prolonged neutropaenia in haematology patients receiving fluoroquinolone and fluconazole prophylaxis: A prospective observational safety study

BackgroundGuidelines advocate >7 d of broad-spectrum antibiotics for unexplained fever (UF) during neutropaenia. However, effective antimicrobial prophylaxis reduces the incidence of gram-negative infections, which may allow shorter treatment. This study evaluates the safety of discontinuing empirical broad-spectrum antibiotics if no microbial source is documented after an initial work-up of 72 h.MethodsProspective observational study at a tertiary-care haematology-unit in patients suffering from haematologic malignancies and treatment-induced prolonged neutropaenia of ?10 d. Oral fluoroquinolone and fluconazole prophylaxis was given from day 1. Fever was empirically treated with imipenem which was discontinued after 72 h if, following a standardised protocol, no infectious aetiology was documented. Duration of fever, antimicrobial therapy and overall mortality were registered.ResultsOne hundred and sixty six patients were evaluated during 276 neutropaenic episodes. One hundred and thirty six patients (82.5%) experienced ?1 febrile episode. A total of 317 febrile episodes were observed, of which 177 (56%) were diagnosed as UF. In 135 febrile episodes (43%), a probable/definite infectious origin was documented. Mean duration of fever in neutropaenic periods with 1 febrile episode was 5 d, and mean time of treatment with imipenem was 4.7 d. In patients without documented infection, mean time of imipenem treatment was only 3.7 d. Overall mortality 30 d after neutrophil recovery was 3.6% (6/166); no patient died from untreated bacterial infection.ConclusionDiscontinuation of broad-spectrum antibiotics during neutropaenia in haematology patients on fluoroquinolone and fluconazole prophylaxis is safe, provided that no infectious aetiology is established after 72 h.     

Outcome of cervical carcinoma with locoregional lymph node involvement by FDG-PET

PurposeTo assess the outcome of cervical carcinoma with positive nodes on fluorodesoxyglucose positon emission tomography scans (FDG-PET).Patients and methodsPatients with cervical carcinoma who had pelvic and/or para-aortic lymph nodes involvement by FDG-PET and treated with a curative intent from 2003 to 2007 were retrospectively studied. All patients received pelvic (and possibly para-aortic) radiotherapy with chemotherapy, followed by brachytherapy, and possibly surgery. The first site of relapse was classified as follows: local, nodal (pelvic or para-aortic) or metastatic.ResultsForty patients were included the study. Median age was 47 years (range: 28–78). Thirty patients had nodal involvement limited to pelvic area and ten had a para-aortic involvement. Median follow-up was 42.5 months (range: 11–85). There were 22 relapses and 20 deaths: 20 due to relapse and one due to late toxicity. Three-year survival is 50 % (95 % confidence interval [CI]: 36–65). First relapse was: metastatic for 33 % (13/40), local for 20 % (8/40) and isolated nodal for 5 % (2/40). Multivariate analysis has revealed that only staging according to International Federation of Gynecology and Obstetrics (FIGO) and para-aortic involvement had a significant impact on survival. Three-year survival was 58 % (CI: 39–74) and 24 % (CI: 7–57) (P = 0.009) in patient without and with para-aortic involvement, respectively.ConclusionPara-aortic involvement by FDG-PET is a significant prognostic factor for overall survival. Local control at primary site remains of paramount importance for patient with nodal involvement. Isolated nodal failures are scarce.     

Groin recurrence in patients with early vulvar cancer following superficial inguinal node dissection

ObjectiveTo investigate the causes of groin recurrence in patients with vulval cancer who previously had negative nodes following superficial inguinal node dissection (SIND).Material and methodsForty-one patients with squamous cell carcinoma of the vulva (stage I or II) were operated upon. The primary treatment was wide local excision with 2 cm safety margin and superficial inguinal lymphadenectomy. Six patients had ipsilateral and one patient had bilateral groin recurrence. Those patients were subjected to deep inguinal node dissection (one patient required bilateral node dissection).ResultsThe mean age at time of diagnosis was 59 years (range 51–68). The median follow-up period for all patients was 63 months (range 24–71) and that of the recurrent cases was 20 months (range 12–38). The mean depth of invasion of the recurrent cases was 5.5 mm (range 5–5.9 mm) and the mean diameter of the primary tumor in recurrent cases was 3.8 cm (range 3–4.5 cm). All recurrent cases had a high grade of the primary tumor. The median interval to recurrence was 21 months (range 12–57). The groin recurrence rate after negative SIND was 17% (7/41 patients).The mean number of nodes resected per groin was eight (range 1–17). The nodes ranged in size from 0.2 to 4.0 cm.ConclusionCarcinoma of the vulva with the following criteria (size of tumor is greater than 3 cm, depth of invasion greater than 5 mm, and high grade tumors) is at high risk of recurrence.