Clinical experiences with online adaptive radiotherapy of vulvar carcinoma.

BACKGROUND AND PURPOSE: Radiotherapy for vulvar carcinoma is challenging due to relatively high risk of locoregional disease recurrence, a technically challenging target, and postoperative lymphocele, and a high risk radiation sequelae. We aim to explore, if it is possible to reduce dose to normal tissue, while maintaining CTV coverage for this patient group with online adaptive radiotherapy. MATERIALS AND METHODS: 20 patients with vulvar carcinoma (527 fractions) were treated with online adaptation on a Varian Ethos accelerator. Setup CBCTs were acquired daily for adaptive planning. Verification CBCTs were acquired immediately prior to dose delivery. CTV dose coverage and dose to bladder and rectum were extracted from the scheduled and adapted plans as well as from adapted plans recalculated based on verification CBCTs. In addition, analysis of the decision of the adaptive procedure was performed for 17 patients (465 fractions). RESULTS: Mean CTV D95% and standard deviation was 98% ± 5% for the scheduled plan compared to 100.0 ± 0.3% and 100.0 ± 0.8% for the adapted plan on the setup and verification CBCT respectively. Dose to OARs varied substantially and did not show any benefit from adaption itself, however a margin reduction was implemented after the first patients treated. The adapted plan was chosen for 63.5% of the fractions and dominant reasons for not adapting were 'no significant dosimetric gain' (75 fractions, 14%) and 'Medical doctor (MD) not available for treatment' (50 fractions, 9.5%). The median adaption time was 15 min and the 25th and 75th percentile was 12 and 17 min, respectively. CONCLUSION: CTVs and PTVs dose coverage were significantly improved with adaptation compared to image-guided RT. This gain was robust during the treatment time.

Treatment and outcomes of a Danish ovarian cancer population.

INTRODUCTION: Ovarian cancer has the highest mortality rate among gynaecological cancers and is the tenth most frequent cancer among women. 80% of patients with advanced stage disease will experience a progression either during or after treatment. METHODS: This was a retrospective, observational study of all women referred to adjuvant or neoadjuvant treatment for ovarian cancer between 1 June 2013 and 31 May 2014 at two university hospitals in Denmark. RESULTS: We included 142 women diagnosed with ovarian cancer. The median overall survival from diagnosis was 48.5 months (95% confidence interval (CI): 36.6-57.9 months). Median survival after the first, second, third, fourth and fifth progression was 19.3 (95% CI: 13.9-27-3), 11.4 (95% CI: 7.7-18.8), 9.5 (95% CI: 6.3-12.7), 8.3 (95% CI: 7.6-11.5) and 5.6 (95% CI: 2.9-not assessed) months, respectively. Median progression-free survival from diagnosis was 15.6 months (95% CI: 14.3-18.4 months). Median progression-free survival after first, second, third, fourth and fifth progression was 9.2 (95% CI: 7.7-10.6), 6.0 (95% CI: 3.5-7.7), 3.3 (95% CI: 2.6-4.6), 4.9 (95% CI: 3.6-8.3) and 3.0 (95% CI: 2.4-5.7) months, respectively. The most frequently used treatment at first progression was carboplatin and pegylated liposomal doxorubicin (n = 37). The most used non-platinum containing treatment at progression was pegylated liposomal doxorubicin (n = 26) followed by paclitaxel (n = 23). CONCLUSIONS: Ovarian cancer remains a highly aggressive disease with most patients diagnosed in advanced stages. Treatment has not changed much in the past 15 years and the same is evident for the overall survival. FUNDING: Tobias Berg received an unrestricted research grant from the Danish Cancer Society. TRIAL REGISTRATION: not relevant.

Gemcitabine for recurrent ovarian cancer - a systematic review and meta-analysis.

INTRODUCTION: More than 80 % of women with advanced ovarian cancer relapse either during or after adjuvant therapy. Platinum-sensitive women are rechallenged with a platinum-combination therapy and platinum-resistant women are challenged with non-platinum drugs. Gemcitabine is one of many treatments that can be used both as single-agent or as combination therapy for the treatment of recurrent ovarian cancer. METHODS: We included all randomised controlled trials investigating patients treated with gemcitabine for recurrent ovarian cancer and reporting data on overall survival, progression-free survival and toxicity. CENTRAL, EMBASE and MEDLINE were searched on the 31st of May 2019. RESULTS: We included six randomised controlled trials that evaluated gemcitabine either alone or as combination therapy. Two studies compared gemcitabine to pegylated liposomal doxorubicin in women with platinum-resistant recurrent ovarian cancer. Difference in overall and progression-free survival was non-significant. Gemcitabine treatment was associated with significantly more neutropenia, whereas pegylated liposomal doxorubicin was associated with significantly more hand-foot syndrome. One study evaluated carboplatin and gemcitabine to carboplatin. Difference in overall survival was non-significant, but progression-free survival was longer with gemcitabine and carboplatin (HR: 0.72, 95% CI 0.58-0.9). One study evaluated gemcitabine with gemcitabine and pertuzumab. Overall survival and progression-free survival was similar between the two arms. One study compared gemcitabine and carboplatin to gemcitabine, carboplatin and bevacizumab. Overall survival was similar in the two arms. Progression-free survival was significantly better in the bevacizumab arm (HR 0.48 95% CI 0.39-0.61). One study compared etoposide and gemcitabine to etoposide. The study showed similar overall survival and progression-free survival. DISCUSSION: The results show that gemcitabine is an active and safe agent in the treatment of both platinum-sensitive and resistant recurrent ovarian cancer but might highlight the need of new randomised studies in heavily pre-treated patients.

Niraparib plus bevacizumab versus niraparib alone for platinum-sensitive recurrent ovarian cancer (NSGO-AVANOVA2/ENGOT-ov24): a randomised, phase 2, superiority trial.

BACKGROUND: Platinum-based chemotherapy is the foundation of treatment for platinum-sensitive recurrent ovarian cancer, but has substantial toxicity. Bevacizumab and maintenance poly(ADP-ribose) polymerase (PARP) inhibitors both significantly improve efficacy versus standard therapy, primarily in terms of progression-free survival, and offer the potential for chemotherapy-free treatment. AVANOVA2 compared niraparib and bevacizumab versus niraparib alone as definitive treatment for platinum-sensitive recurrent ovarian cancer. METHODS: This open-label, randomised, phase 2, superiority trial in 15 university hospitals in Denmark, Sweden, Finland, Norway, and the USA enrolled women aged 18 years or older with measurable or evaluable high-grade serous or endometrioid platinum-sensitive recurrent ovarian cancer. Patients had to have an Eastern Cooperative Oncology Group performance status of 0-2, and had to have previously received platinum-containing therapy for primary disease but ≤1 prior non-platinum-containing regimen for recurrent disease. Previous treatment with bevacizumab or first-line maintenance PARP inhibitors was permitted. Eligible patients were randomly assigned 1:1 (by random permuted blocks with block sizes of two and four, no masking), stratified by homologous recombination deficiency status and chemotherapy-free interval, to receive once-daily oral niraparib 300 mg alone or with intravenous bevacizumab 15 mg/kg once every 3 weeks until disease progression. The primary endpoint was progression-free survival, assessed by the investigators in the intention-to-treat population after events in at least 62 patients. Safety was analysed in all patients who received at least one dose of study drug. This ongoing trial is registered with ClinicalTrials.gov, number NCT02354131. FINDINGS: Between May 23, 2016, and March 6, 2017, 97 patients were enrolled and randomly assigned: 48 to niraparib plus bevacizumab and 49 to single-agent niraparib. Median follow-up was 16·9 months (IQR 15·4-20·9). Niraparib plus bevacizumab significantly improved progression-free survival compared with niraparib alone (median progression-free survival 11·9 months [95% CI 8·5-16·7] vs 5·5 months [3·8-6·3], respectively; adjusted hazard ratio [HR] 0·35 [95% CI 0·21-0·57], p<0·0001). Grade 3 or worse adverse events occurred in 31 (65%) of 48 patients who received niraparib plus bevacizumab and 22 (45%) of 49 who received single-agent niraparib. The most common grade 3 or worse adverse events in both groups were anaemia (7 [15%] of 48 vs 9 [18%] of 49) and thrombocytopenia (5 [10%] vs 6 [12%]), and hypertension in the combination group (10 [21%] vs 0). Niraparib plus bevacizumab was associated with increased incidences of any-grade proteinuria (10 [21%] of 48 patients vs 0) and hypertension (27 [56%] of 48 vs 11 [22%] of 49) compared with niraparib alone. No treatment-related deaths occurred. INTERPRETATION: The efficacy observed with this chemotherapy-free combination of approved agents in women with platinum-sensitive recurrent ovarian cancer warrants further evaluation. A randomised phase 3 trial investigating niraparib plus bevacizumab versus chemotherapy plus bevacizumab in platinum-sensitive recurrent ovarian cancer is planned. FUNDING: Nordic Society of Gynaecological Oncology and Tesaro.

A phase I study of the PARP inhibitor niraparib in combination with bevacizumab in platinum-sensitive epithelial ovarian cancer: NSGO AVANOVA1/ENGOT-OV24.

BACKGROUND: Combining poly(ADP-ribose) polymerase (PARP) inhibitors with antiangiogenic agents appeared to enhance activity vs PARP inhibitors alone in a randomized phase II trial. MATERIALS AND METHODS: In AVANOVA (NCT02354131) part 1, patients with measurable/evaluable high-grade serous/endometrioid platinum-sensitive ovarian cancer received bevacizumab 15 mg/kg every 21 days with escalating doses of niraparib capsules (100, 200, or 300 mg daily) in a 3 + 3 dose-escalation design. Primary objectives were to evaluate safety and tolerability and to determine the recommended phase II dose (RP2D). RESULTS: Three of 12 enrolled patients had germline BRCA2 mutations. In cycle 1, nine patients experienced grade 3 toxicities: five with hypertension, three with anemia, and one with thrombocytopenia. There was one dose-limiting toxicity (grade 4 thrombocytopenia with niraparib 300 mg), thus the RP2D was bevacizumab 15 mg/kg with niraparib 300 mg. The response rate was 50%; disease was stabilized in a further 42%. Median progression-free survival was 11.6 (95% confidence interval 8.4-20.1) months. Niraparib pharmacokinetics were consistent with historical single-agent data. Overlapping exposure was observed across the dose ranges tested on days 1 and 21. CONCLUSIONS: There was one dose-limiting toxicity; other adverse events were typical PARP inhibitor and antiangiogenic class effects. Niraparib-bevacizumab showed promising activity; Part 2 (vs bevacizumab) was recently reported and phase III comparison with standard-of-care therapy is planned.

Cerebral infarction after fractionated stereotactic radiation therapy of benign anterior skull base tumors.

BACKGROUND: The purpose of this study was to examine the occurrence of cerebral infarction (ischemic stroke), in a large combined cohort of patients with anterior skull base meningiomas, pituitary adenomas and craniopharyngiomas, after fractionated stereotactic radiation therapy (FSRT). MATERIAL AND METHODS: All patients, 18 years and older, with anterior skull base meningiomas, pituitary adenomas and craniopharyngiomas, treated with fractionated stereotactic radiation, in our center, from January 1999 to December 2015 were identified. In total 169 patients were included. The prescription dose to the tumor was 54 Gy for 164 patients (97%) and 46.0-52.2 Gy for 5 patients (3%). Cases of cerebral infarctions subsequent to FSRT were identified from the Danish National Patient Registry and verified with review of case notes. The rate of cerebral infarction after FSRT was compared to the rate in the general population with a one sample t-test after standardization for age and year. We explored if age, sex, disease type, radiation dose and dose per fraction was associated with increased risk of cerebral infarction using univariate Cox models. RESULTS: At a median follow-up of 9.3 years (range 0.1-16.5), 7 of the 169 patients (4.1%) developed a cerebral infarction, at a median 5.7 years (range 1.2-11.5) after FSRT. The mean cerebral infarction rate for the general population was 0.0035 and 0.0048 for the FSRT cohort (p = 0.423). Univariate cox models analysis showed that increasing age correlated significantly with the cerebral infarction risk, with a hazard ratio of 1.090 (p = 0.013). CONCLUSION: Increased risk of cerebral infarction after FSRT of anterior skull base tumors was associated with age, similar to the general population. Our study revealed that FSRT did not introduce an excess risk of cerebral infarction.

Cervical cancer staging, pretreatment planning, and surgical treatment in the Nordic countries-Survey from the Surgical Subcommittee of the Nordic Society of Gynecological Oncology.

INTRODUCTION: Women with cervical cancer in the Nordic countries are increasingly undergoing pretreatment imaging by ultrasound, magnetic resonance imaging (MRI), positron emission tomography-computed tomography (PET-CT) or computed tomography, or sentinel lymph node procedure. The present survey reports the influence of pretreatment imaging findings on the recorded clinical International Federation of Gynecology and Obstetrics (FIGO) stage in Nordic countries and its impact on treatment planning and preferred surgical approach in cervical cancer. MATERIAL AND METHODS: The Nordic Society of Gynecological Oncology Surgical Subcommittee developed a questionnaire-based survey that was conducted from 1 January to 31 March 2017. All the 22 Nordic Gynecological Oncology Centers (Denmark 5, Finland 5, Iceland 1, Norway 4, and Sweden 7) were invited to participate. RESULTS: The questionnaires were returned by 19 of 22 (86.3%) centers. The median number (range) of women with cervical cancer treated at each center annually was 32 (15-120). In 58% (11/19) of the centers, imaging findings were reported to influence the clinical staging. MRI in combination with PET-CT was the preferred imaging method and the results influenced treatment planning. Robotic-assisted radical hysterectomy was the preferred surgical method in 72% (13/18) of the centers. Sentinel lymph node procedure was not routinely implemented in the majority of the Nordic centers. CONCLUSION: More than half of the Nordic Gynecological Oncology Centers already report a clinical FIGO stage influenced by pretreatment imaging findings. The trend in preferred treatment is robotic-assisted radical hysterectomy and the sentinel lymph node procedure is gradually being introduced.

18 F-FDG PET/CT for planning external beam radiotherapy alters therapy in 11% of 581 patients.

BACKGROUND: 18 F-FDG PET/CT (FDG PET/CT) used in radiotherapy planning for extra-cerebral malignancy may reveal metastases to distant sites that may affect the choice of therapy. AIM: To investigate the role of FDG PET/CT on treatment strategy changes induced by the use of PET/CT as part of the radiotherapy planning. 'A major change of treatment strategy' was defined as either including more lesions in the gross tumour volume (GTV) distant from the primary tumour or a change in treatment modalities. METHODS: The study includes 581 consecutive patients who underwent an FDG PET/CT scan for radiotherapy planning in our institution in the year 2008. All PET/CT scans were performed with the patient in treatment position with the use of immobilization devices according to the intended radiotherapy treatment. All scans were evaluated by a nuclear medicine physician together with a radiologist to delineate PET-positive GTV (GTV-PET). RESULTS: For 63 of the patients (11%), the PET/CT simulation scans resulted in a major change in treatment strategy because of the additional diagnostic information. Changes were most frequently observed in patients with lung cancer (20%) or upper gastrointestinal cancer (12%). In 65% of the patients for whom the PET/CT simulation scan revealed unexpected dissemination, radiotherapy was given - changed (n = 38) or unchanged (n = 13) according to the findings on the FDG PET/CT. CONCLUSION: Unexpected dissemination on the FDG PET/CT scanning performed for radiotherapy planning caused a change in treatment strategy in 11% of 581 patients.

Visual outcome, endocrine function and tumor control after fractionated stereotactic radiation therapy of craniopharyngiomas in adults: findings in a prospective cohort.

BACKGROUND: The purpose of this study was to examine visual outcome, endocrine function and tumor control in a prospective cohort of craniopharyngioma patients, treated with fractionated stereotactic radiation therapy (FSRT). MATERIAL AND METHODS: Sixteen adult patients with craniopharyngiomas were eligible for analysis. They were treated with linear accelerator-based FSRT during 1999-2015. In all cases, diagnosis was confirmed by histological analysis. The prescription dose to the tumor was 54 Gy (median, range 48-54) in 1.8 or 2.0 Gy per fraction, and the maximum radiation dose to the optic nerves and chiasm was 54.2 Gy (median, range 48.6-60.0) for the cohort. Serial ophthalmological and endocrine evaluations and magnetic resonance imaging (MRI) scans were performed at regular intervals. Median follow-up was 3.3 years (range 1.1-14.1), 3.7 years (range 0.8-15.2), and 3.6 years (range 0.7-13.1) for visual outcome, endocrine function, and tumor control, respectively. RESULTS: Visual acuity impairment was present in 10 patients (62.5%) and visual field defects were present in 12 patients (75%) before FSRT. One patient developed radiation-induced optic neuropathy at seven years after FSRT. Thirteen of 16 patients (81.3%) had pituitary deficiency before FSRT, and did not develop further pituitary deficiency after FSRT. Mean tumor volume pre-FSRT was 2.72 cm3 (range 0.20-9.90) and post-FSRT 1.2 cm3 (range 0.00-13.10). Tumor control rate was 81.3% at two, five, and 10 years after FSRT. CONCLUSIONS: FSRT was relatively safe in this prospective cohort of craniopharyngiomas, with only one case of radiation-induced optic neuropathy and no case of new endocrinopathy. Tumor control rate was acceptable.

Visual outcome after fractionated stereotactic radiation therapy of benign anterior skull base tumors.

To determine visual outcome including the occurrence of radiation induced optic neuropathy (RION) as well as tumor control after fractionated stereotactic radiation therapy (FSRT) of benign anterior skull base meningiomas or pituitary adenomas. Thirty-nine patients treated with FSRT for anterior skull base meningiomas and 55 patients treated with FSRT for pituitary adenomas between January 1999 and December 2009 with at least 2 years follow-up were included. Patients were followed up prospectively with magnetic resonance imaging scans, visual acuity and visual field examinations. RION was found in four (10%) patients with anterior skull base meningiomas and seven patients (13%) with pituitary adenomas. The five-year actuarial freedom from 25% RION visual field loss was 94% following FSRT. Actuarial 2-, 5- and 10-year tumor control rates were 100, 88.4 and 64.5% for anterior skull base meningiomas and 100, 98.2 and 94.9% for pituitary adenomas, respectively. Patients with an impaired visual field function pre-FSRT were more likely to experience worsened function (p = 0.016). We found that RION, was a relatively uncommon event, in a large prospective cohort of patients that were systematically monitored following FSRT of benign anterior skull base tumors. Long term tumor control was favorable, especially for pituitary adenomas.

Fractionated stereotactic radiotherapy of vestibular schwannomas accelerates hearing loss.

OBJECTIVE: To evaluate long-term tumor control and hearing preservation rates in patients with vestibular schwannoma treated with fractionated stereotactic radiotherapy (FSRT), comparing hearing preservation rates to an untreated control group. The relationship between radiation dose to the cochlea and hearing preservation was also investigated. METHODS AND MATERIALS: Forty-two patients receiving FSRT between 1997 and 2008 with a minimum follow-up of 2 years were included. All patients received 54 Gy in 27-30 fractions during 5.5-6.0 weeks. Clinical and audiometry data were collected prospectively. From a "wait-and-scan" group, 409 patients were selected as control subjects, matched by initial audiometric parameters. Radiation dose to the cochlea was measured using the original treatment plan and then related to changes in acoustic parameters. RESULTS: Actuarial 2-, 4-, and 10-year tumor control rates were 100%, 91.5%, and 85.0%, respectively. Twenty-one patients had serviceable hearing before FSRT, 8 of whom (38%) retained serviceable hearing at 2 years after FSRT. No patients retained serviceable hearing after 10 years. At 2 years, hearing preservation rates in the control group were 1.8 times higher compared with the group receiving FSRT (P=.007). Radiation dose to the cochlea was significantly correlated to deterioration of the speech reception threshold (P=.03) but not to discrimination loss. CONCLUSION: FSRT accelerates the naturally occurring hearing loss in patients with vestibular schwannoma. Our findings, using fractionation of radiotherapy, parallel results using single-dose radiation. The radiation dose to the cochlea is correlated to hearing loss measured as the speech reception threshold.

Stereotactic radiotherapy and radiosurgery in pediatric patients: analysis of indications and outcome.

INTRODUCTION: We describe indications, outcomes, and risk profiles of fractionated stereotactic radiotherapy (SRT) and single fraction "radiosurgery" (SRS) in pediatric patients compared to the adult population and evaluate the causal role of SRS and SRT in inducing new neurological complications. MATERIALS AND METHODS: Six children with AVMs and 12 children with neoplastic diseases were prospectively followed for >2 years after SRT/S. The survival, control of pathology, and specified neurological complications were analyzed. In tumor patients, the median overall survival time was 45 months (range 5-103) and the median progression free survival time was 35 months (range 5-98). RESULTS: Control or regression of the tumor was obtained in 83% of patients with neoplastic disease. Three patients with malignant tumors died from disease progression. In AVMs the median time follow up was 52 months (range 27-100). All AVMs were obliterated. New neurological deficits occurred in 67%. SRT/S was considered the direct cause in 25%. All the neurological deficiencies related to SRT/S were focal and related to the irradiated areas. In tumor patients, midline lesions, malignant diagnosis, and additional treatment with surgery, chemotherapy, and craniospinal irradiation seemed to increase the risk of new deficits after SRT/S. In AVM patients, a high Spetzler-Martin grade seemed to carry a higher complication risk. CONCLUSION: The risk of uncontrolled tumor disease or the risk of hemorrhage of non-obliterated AVM must be balanced against the overall risks and benefits of SRT/S. Following SRT/S, the risk of worsening pre-existing deficits is relatively high. The risk of inducing new long-term deficits is relatively low.

Complications following linear accelerator based stereotactic radiation for cerebral arteriovenous malformations.

PURPOSE: Primarily, gamma knife centers are predominant in publishing results on arteriovenous malformations (AVM) treatments including reports on risk profile. However, many patients are treated using a linear accelerator-most of these at smaller centers. Because this setting is different from a large gamma knife center, the risk profile at Linac departments could be different from the reported experience. Prescribed radiation doses are dependent on AVM volume. This study details results from a medium sized Linac department center focusing on risk profiles. METHOD AND MATERIALS: A database was searched for all patients with AVMs. We included 50 consecutive patients with a minimum of 24 months follow-up (24-51 months). RESULTS: AVM occlusion was verified in 78% of patients (39/50). AVM occlusion without new deficits (excellent outcome) was obtained in 44%. Good or fair outcome (AVM occlusion with mild or moderate new deficits) was seen in 30%. Severe complications after AVM occlusion occurred in 4% with a median interval of 15 months after treatment (range, 1-26 months). CONCLUSIONS: We applied an AVM grading score developed at the Mayo Clinic to predict probable outcome after radiosurgery in a large patient population treated with Gamma knife. A cutoff above and below a score of 1.5 could not discriminate between the likelihood of having an excellent outcome (approximately 45%). The chance of having an excellent or good outcome was slightly higher in patients with an AVM score below 1.5 (64% vs. 57%).

Influence of 2-(18F) fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography on recurrent ovarian cancer diagnosis and on selection of patients for secondary cytoreductive surgery.

The objective of this prospective study was to compare the sensitivities and the specificities of combined 2-(F) fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (PET/CT), abdominal/transvaginal ultrasound (US), and CT for diagnosing recurrent ovarian cancer (OC) and to evaluate the influence of PET/CT on referral of patients with solitary recurrence to secondary cytoreductive surgery. From April 2005 to November 2007, 60 patients were consecutively included to PET/CT 68 times. The inclusion criteria were remission of 3 months or longer and recurrent OC suspected from physical examination, US, or increasing cancer antigen 125 (CA125) level (>50 U/mL or >15% above baseline level). Recurrent OC was diagnosed 58 times in 52 patients. The sensitivities of US, CT, and PET/CT for diagnosing recurrence were 66% (P = 0.003), 81% (P = 0.0001), and 97% (P < 0.0001), respectively. The specificity of US, CT, and PET/CT for diagnosing recurrence was 90%. Positron emission tomography/CT diagnosed recurrence in 19 (66%) of 29 patients without recurrence according to US and in 10 (50%) of 20 patients without recurrence after CT. Multiple recurrent tumors were found using PET/CT in 27 (69%) of 39 patients with solitary tumors on US and in 8 (42%) of 19 patients with solitary tumors on CT. We conclude that the diagnostic value of PET/CT for detecting recurrent OC was higher than those of US and CT and that PET/CT more accurately identified patients with solitary recurrence. However, prospective clinical trials are needed to specify the characteristics of patients most likely to undergo complete secondary surgery and to further clarify the role of PET/CT in selecting patients for secondary surgery.

Vaginal rupture caused by transvaginal ultrasonography in follow-up for ovarian cancer.

Vaginal rupture is a rare complication of hysterectomy. It is, among others, related to age and the incidence is higher in postmenopausal women. The rupture can occur spontaneously or in relation to clinical follow-up. In ovarian cancer the follow-up after surgery includes clinical examination, cancer antigen (CA)-125, and transabdominal and transvaginal ultrasonography. We experienced vaginal rupture in three patients with ovarian cancer. All patients had undergone surgery for ovarian cancer and were receiving chemotherapy. The rupture occurred shortly after transvaginal ultrasonography, performed by separate radiologists specialised in ultrasonography. All patients had acute surgery without any complications. Caution should be taken when performing transvaginal ultrasonography in hysterectomised patients and the complication of vaginal rupture should always be borne in mind.

Local control and survival in patients with soft tissue sarcomas treated with limb sparing surgery in combination with interstitial brachytherapy and external radiation.

PURPOSE: The purpose of this study was to evaluate local control, survival and complication rate after treatment of soft tissue sarcoma (STS) with limb-sparing surgery combined with pulsed-dose rate (PDR) interstitial brachytherapy (BRT) and external beam radiotherapy (EBRT). PATIENTS AND METHODS: A retrospective review of 39 adult patients (female/male=25/14, mean age 51(range 21-78) years) with STS who underwent primary limb-sparing surgery combined with PDR BRT (20Gy) and additional post-operative EBRT (50Gy) during the years 1995-2004. RESULTS: Five patients developed local recurrence after a mean follow-up of 3.4 (1.5-5.9) years. The probability of local recurrence free 5 years survival was 83%. At the time of follow-up 10 patients had died (mean follow-up 2.3 (0.8-7.1) years) and 29 patients were still alive (mean follow-up 5.9 (2.1-11.2) years). The overall 5-year survival rate was 76%. Nineteen (49%) patients suffered from some degree of decreased force or function of the affected extremity, 16 (41%) suffered from oedema, 12 (31%) had persistent pain, 8 (21%) suffered from wound complications, and in 4 (10%) of these patients plastic surgery were required. CONCLUSION: Limb sparing surgery, combined with PDR BRT and EBRT can result in good local control in patients with soft tissue sarcomas. BRT is an effective modality with good cosmetic results and acceptable toxicity.

The diagnostic value of PET/CT scanning in patients with cervical cancer: a prospective study.

OBJECTIVE: To investigate the clinical value of PET/CT as a supplement to FIGO staging in patients with cervical cancer stage >or=1B. METHODS: This prospective study included 120 consecutive patients. After staging, a whole-body PET/CT scan was performed and these examinations were divided into two groups: (1) patients suitable for radical hysterectomy including lymph node dissection and (2) patients referred to combined chemo/radiation therapy. The results were compared to histopathological findings and/ or follow-up. RESULTS: Twenty-seven patients underwent radical surgery; four of these had PET/CT scans revealing pathological foci in the pelvis. Three (11%) were true positive; one was false positive. Twenty-two patients had true negative PET/CT scans concerning pelvic lymph nodes. One patient had a false negative node. For these patients, we found the positive predictive value (PPV) to be 75%, negative predictive value (NPV) 96%, sensitivity 75%, specificity 96%. Regarding para-aortal nodal disease in the total population of 119 patients, 15 patients had true positive scans. The number of true negatives was 103, resulting in PPV 94%, NPV 100%, sensitivity 100% and specificity 99%. PET/CT scans showed distant metastases in 19 patients, 10 were true positive and nine were false positive. The remaining 100 patients were considered true negative for distant metastases and for these patients, we found PPV 63%, NPV 100%, sensitivity 100% and specificity 94%. CONCLUSIONS: Whole-body FDG PET/CT scanning for newly diagnosed cervical cancer FIGO stage >or=1B has a high sensitivity and specificity, and can be a valuable supplement to the FIGO staging procedure.

Phase II study on stereotactic body radiotherapy of colorectal metastases.

Surgical resection provides long term survival in approximately 30% of patients with colorectal carcinoma (CRC) liver metastases. However, only a limited number of patients with CRC-metastases are amendable for surgery. We have tested the effect of stereotactic body radiotherapy (SBRT) in the treatment of inoperable patients with CRC-metastases. Sixty-four patients with a total number of 141 CRC-metastases in the liver (n = 44), lung (n = 12), lymph nodes (n = 3), suprarenal gland (n = 1) or two organs (n = 4) were treated with SBRT with a central dose of 15 Gy x 3 within 5-8 days. Median follow-up was 4.3 years. After 2 years, actuarial local control was 86% and 63% in tumor and patient based analysis, respectively. Nineteen percent were without local or distant progression after 2 years and overall survival was 67, 38, 22, 13, and 13% after 1, 2, 3, 4 and 5 years, respectively. One patient died due to hepatic failure, one patient was operated for a colonic perforation and two patients were conservatively treated for duodenal ulcerations. Beside these, only moderate toxicities such as nausea, diarrhoea and skin reactions were observed. SBRT in patients with inoperable CRC-metastases resulted in high probability of local control and promising survival rate. One toxic death and few severe reactions were observed. For the majority of patients, the treatment related toxicity was moderate.

Phase-II study on stereotactic radiotherapy of locally advanced pancreatic carcinoma.

BACKGROUND AND PURPOSE: The majority of patients with pancreatic cancer have advanced disease at the time of diagnosis and are not amenable for surgery. Stereotactic radiotherapy (SRT) may be an alternative treatment for patients with locally advanced disease. The effect of SRT was investigated in the present phase-II trial. PATIENTS AND METHODS: Twenty-two patients with locally advanced and surgically non-resectable, histological proven pancreatic carcinoma were included into the trial. The patients were immobilized by the Elekta stereotactic body frame (SBF) or a custom made body frame. SRT was given on standard LINAC with standard multi-leaf collimator. Central dose was 15 Gyx3 within 5-10 days. RESULTS: Evaluation of response was found to be very difficult due to radiation and tumour related tissue reaction. Only two patients (9%) were found to have a partial response (PR), the remaining had no change (NC) or progression (PD) after treatment. Six patients had local tumour progression, but only one patient had an isolated local failure without simultaneous distant metastasis. Median time to local or distant progression was 4.8 months. Median survival time was 5.7 months and only 5% were alive 1 year after treatment. Acute toxicity reported 14 days after treatment was pronounced. There was a significant deterioration of performance status (P=0.008), more nausea (P=0.001) and more pain (P=0.008) after 14 days compared with base-line. However, 8 of 12 patients (66%) improved in performance status, scored less nausea, pain, or needed less analgesic drugs at 3 months after treatment. Four patients suffered from severe mucositis or ulceration of the stomach or duodenum and one of the patients had a non-fatal ulcer perforation of the stomach. CONCLUSIONS: SRT was associated with poor outcome, unacceptable toxicity and questionable palliative effect and cannot be recommended for patients with advanced pancreatic carcinoma.