Which technique for radiation is most beneficial for patients with locally advanced cervical cancer? Intensity modulated proton therapy versus intensity modulated photon treatment, helical tomotherapy and volumetric arc therapy for primary radiation - an intraindividual comparison.

BACKGROUND: To compare highly sophisticated intensity-modulated radiotherapy (IMRT) delivered by either helical tomotherapy (HT), RapidArc (RA), IMRT with protons (IMPT) in patients with locally advanced cervical cancer. METHODS AND MATERIALS: Twenty cervical cancer patients were irradiated using either conventional IMRT, VMAT or HT; ten received pelvic (PEL) and ten extended field irradiation (EFRT). The dose to the planning-target volume A (PTV_A: cervix, uterus, pelvic ± para-aortic lymph nodes) was 1.8/50.4 Gy. The SIB dose for the parametrium (PTV_B), was 2.12/59.36 Gy. MRI-guided brachytherapy was administered with 5 fractions up to 25 Gy. For EBRT, the lower target constraints were 95% of the prescribed dose in 95% of the target volume. The irradiated small bowel (SB) volumes were kept as low as possible. For every patient, target parameters as well as doses to the organs at risk (SB, bladder, rectum) were evaluated intra-individually for IMRT, HT, VMAT and IMPT. RESULTS: All techniques provided excellent target volume coverage, homogeneity, conformity. With IMPT, there was a significant reduction of the mean dose (Dmean) of the SB from 30.2 ± 4.0 Gy (IMRT); 27.6 ± 5.6 Gy (HT); 34.1 ± 7.0 (RA) to 18.6 ± 5.9 Gy (IMPT) for pelvic radiation and 26.3 ± 3.2 Gy (IMRT); 24.0 ± 4.1 (HT); 25.3 ± 3.7 (RA) to 13.8 ± 2.8 Gy (IMPT) for patients with EFRT, which corresponds to a reduction of 38-52% for the Dmean (SB). Futhermore, the low dose bath (V10Gy) to the small bowel was reduced by 50% with IMPT in comparison to all photon techniques. Furthermore, Dmean to the bladder and rectum was decresed by 7-9 Gy with IMPT in patents with pelvic radiation and EFRT. CONCLUSION: All modern techniques (were proved to be dosimetrically adequate regarding coverage, conformity and homogeneity of the target. Protons offered the best sparing of small bowel and rectum and therefore could contribute to a significant reduction of acute and late toxicity in cervical cancer treatment.

Optimizing image guidance frequency and implications on margins for gynecologic malignancies.

BACKGROUND: To analyze setup deviations using daily megavoltage computed tomography (MVCT) and to evaluate three MVCT frequency reducing protocols for gynecologic cancer patients treated with helical tomotherapy. METHODS: We recorded the setup errors of 56 patients with gynecological cancer observed throughout their whole course by matching their daily MVCT with the planning CT. Systematic and random errors were calculated on a patient and population basis. We defined three different protocols corresponding to MVCTs from the first five fractions (FFF), the first ten fractions (FTF) or from the first and third weeks (505). We compared theoretical. setup errors calculated using these 5 or 10 early MVCT scans with the actual errors found with the remaining fractions to to analyze the residual deviations. RESULTS: The total systematic (random) deviations had means of -2.0 (3.8)mm, 0.5 (3.4)mm, 0.5 (6.1)mm and -0.5° (0.9°) in vertical (V), longitudinal (LO), lateral (LA), and roll (R) directions, respectively. The proposed three MVCT protocols resulted in minor residual deviations. In all three protocols, 95% of all calculated residual deviations were less than or equal to 5 mm in all 3 directions. When examining the additional minimal CTV-PTV setup margins that were calculated based on these residual deviations, the 505 protocol would have allowed smaller margins than the FFF and FTF protocol, particularly in the V direction. CONCLUSIONS: For patients with gynecologic cancer, the 505-protocol led to the lowest residual deviations and therefore might offer the best approach in reducing the frequency of pre-treatment MVCTs.

Neonatal outcome in infants of patients with radical vaginal trachelectomy.

OBJECTIVE: Radical vaginal trachelectomy (RVT) as a fertility-preserving surgery in patients with early-stage cervical cancer is proven to be oncologically safe. After RVT, pregnancy rates vary between 40 % and 80 %. Outcome of infants is complicated by a preterm delivery rate of 30 ­ 50 %. We investigated pregnancy and neonatal outcome after RVT. METHODS: A total of 154 patients with cervical cancer underwent RVT between March 1995 and February 2008. Desire to conceive, pregnancy data, and neonatal outcome were prospectively recorded. Infants' data were pair-matched to data of a control group according to weeks of gestation. Bayley scales of infant development scores were recorded in the group of preterm-delivered infants. RESULTS: Fifty-five women who underwent RVT gave birth to 58 children. Twenty-five (43 %) pregnancies were complicated by preterm rupture of membranes. Thirty infants (52 %) were born preterm, of with 17 (29 %) were < 32 gestational weeks (GW) and seven (12 %) were < 28 GW. There were significantly more premature rupture of membranes in pregnancies after RVT. Despite a higher occurrence of postnatal infections in newborns of mothers who underwent RVT, long-term outcomes are not affected negatively. Regarding overall morbidity, a trend to fewer postnatal complications, compared with the control group, was found. CONCLUSION: Postnatal morbidity in infants of women who underwent RVT, based on trend, is decreased compared with controls. Intense medical observation and treatment during pregnancy, birth, and neonatal period may explain this finding. Neonates in the RVT group have a non-significantly elevated risk for postnatal infections. They do not show an additional risk due to the maternal operation. Their long-term postnatal outcome is not affected negatively.

Pregnancy after lymphadenectomy and neoadjuvant chemotherapy followed by radical vaginal trachelectomy in FIGO stage IB1 cervical cancer.

OBJECTIVE: To report a case of full-term delivery after laparoscopic lymphadenectomy and neoadjuvant chemotherapy followed by radical vaginal trachelectomy in bulky stage IB1 cervical cancer. DESIGN: Case report. SETTING: University hospital. PATIENT(S): A 27-year-old woman with adenosquamous cervical cancer stage IB1 (4 cm in diameter) that was diagnosed in December 2005. She expressed a wish for fertility-sparing treatment. INTERVENTION(S): A laparoscopic pelvic and para-aortic lymphadenectomy was performed and showed no evidence of lymphatic metastasis. The patient subsequently received chemotherapy with Paclitaxel 200 mg/m2 and Cisplatin 100 mg/m2. The treatment cycle was repeated after 3 weeks with Cisplatin reduced to 50 mg/m2, because of creatinine-increase. Radical vaginal trachelectomy was then performed. After histologic examination, carcinoma of only 2 mm in diameter was found in the final specimen. MAIN OUTCOME MEASURE(S): Oncologic and fertility outcome after neoadjuvant chemotherapy and radical vaginal trachelectomy. RESULT(S): The patient resumed a normal menstrual pattern 6 weeks after surgery. In December 2008, she conceived and carried and infant to full term. Antenatally, she reported no problems during pregnancy except for gestational insulin-dependent diabetes. She gave birth to a baby boy at 38 weeks' gestation by caesarean section. The newborn (weight, 3500 g; length, 52 cm; Apgar scores, 5/8/10; pH value, 7.28) was monitored in a neonatal ward for 24 hours. The patient is currently under outpatient review and has had 5 years of follow-up with no evidence of recurrence. CONCLUSION(S): Neoadjuvant chemotherapy followed by a fertility-sparing surgery may become a valuable option for women with bulky-stage cervical cancer who wish to preserve their fertility potential.

Vaginal-assisted laparoscopic radical hysterectomy: rationale, technique, results.

OBJECTIVE: Total laparoscopic radical hysterectomy (TLRH) makes it difficult to resect adequate vaginal cuff according to tumor size and to avoid tumor spread after opening the vagina. Laparoscopic-assisted radical vaginal hysterectomy (LARVH) is associated with higher risk for urologic complications. METHODS: The vaginal-assisted laparoscopic radical hysterectomy (VALRH) technique comprises 3 steps: (1) comprehensive laparoscopic staging, (2) creation of a tumoradapted vaginal cuff, and (3) laparoscopic transsection of parametria. We retrospectively analyzed data of 122 patients who underwent VALRH for early stage cervical cancer (n=110) or stage II endometrial cancer (n=12) between January 2007 and December 2009 at Charité University Berlin. RESULTS: All patients underwent VALRH without conversion. Mean operating time was 300 minutes, and mean blood loss was 123cc. On average, 36 lymph nodes were harvested. Intra- and postoperative complication rates were 0% and 13.1%, respectively. Resection was in sound margins in all patients. After median follow-up of 19 months, disease-free survival and overall survival for all 110 cervical cancer patients was 94% and 98%, and for the subgroup of patients (n=90) with tumors ≤pT1b1 N0 V0 L0/1 R0, 97% and 98%, respectively. CONCLUSION: VALRH is a valid alternative to abdominal radical hysterectomy and LARVH in patients with earlystage cervical cancer and endometrial cancer stage II with minimal intraoperative complications and identical oncologic outcomes.

Sonographic monitoring of systemic and local methotrexate (MTX) therapy in patients with intact interstitial pregnancies.

OBJECTIVE: After the confirmation of an intact interstitial pregnancy through sonographic diagnosis and laparoscopy, systemic and local methotrexate therapy is a well established conservative treatment to preserve the uterus. The parameters of successful treatment are the course of serum hCG value and sonographic changes. In this case series we describe sonographic monitoring under methotrexate (MTX) application and the residual sonographic findings after completing therapy. METHODS: Three consecutive patients (two singleton and one twin pregnancy) with intact interstitial pregnancies were diagnosed and treated with MTX between 2000 and 2004. During the treatment we recorded the hCG values, maximum size of the interstitial lesion, vitality of the pregnancy, and vascularization. RESULTS: In all patients the sonographic diagnosis of an interstitial pregnancy was confirmed by laparoscopy. Following systemic MTX therapy, the hCG values normalised within 8 weeks in the singleton pregnancies and in 10 weeks in the twin pregnancy. During conservative therapy vascularization in the lesion withered continuously. The size of the primary myometrial lesion decreased at a slow rate and part of the lesion persisted in all three patients. CONCLUSION: Despite decreasing hCG levels, residual sonographic patterns of an interstitial ectopic pregnancy persist in the uterine wall.

Laparoscopic and vaginal repair of uterine scar dehiscence following cesarean section as detected by ultrasound.

INTRODUCTION AND OBJECTIVE: Cesarean section (CS) is the most common operation in obstetrics, with rising incidence in most countries. As a result of this operation late scar dehiscence may occur, which may lead to uterine rupture in a subsequent pregnancy. In this case series we have described sonographic detection of scar dehiscence after CS and feasibility of vaginal or combined laparoscopic and vaginal scar excision and uterine repair. METHODS: Five consecutive patients underwent vaginal or laparoscopic assisted vaginal approach for repair of suspected scar dehiscence following CS, during a 5 year period. In all cases, transvaginal sonography detected suspicious features of scar dehiscence over the anterior uterine wall. Except of one, all patients had reported recurrent pelvic pain and/or irregular menstrual bleedings. Furthermore all patients planned for a further pregnancy. RESULTS: Resection of the uterine defect and re-constitution of the uterine wall was successfully achieved in all five patients. There were no intra-operative complications and none of the patients required blood transfusion. The mean operation time was 117 min (27-192). Presence of scar tissue was confirmed on histology in all specimens. Four patients remained free of symptoms with no evidence of recurrent scar dehiscence on sonography over a median follow up of 30 months (3-46). One patient had an uneventful pregnancy 24 months after scar removal and was delivered by repeat CS at 39 weeks' gestation. CONCLUSION: Patients with a history of CS should undergo transvaginal sonography of the scar region in order to detect latent scar dehiscence in combination with uterine wall thinning prior to planning further pregnancy. In suspected cases, a combined laparoscopic - vaginal or vaginal approach can be employed to repair the defect.

Laparoscopy versus laparotomy in endometrial cancer: first analysis of survival of a randomized prospective study.

STUDY OBJECTIVE: Laparoscopy has been proved to be safe and reliable in staging of patients with endometrial cancer. It has definite advantages over laparotomy, but a comparable survival outcome is still to be verified in prospective randomized trials. DESIGN: Prospective, randomized clinical trial. SETTING: Department of Gynecology, Friedrich Schiller University, Jena, Germany. PATIENTS: One hundred twenty-two women with uterine cancer. INTERVENTIONS: Laparotomy and laparoscopy. MEASUREMENTS AND MAIN RESULTS: Sixty-three patients were allocated to the laparoscopy arm, and 59 were allocated to the laparotomy arm. Median follow-up for all patients was 44 months (range 5-96 months). Eight patients (12.6%) in the laparoscopy group had a recurrence versus five patients (8.5%) in the laparotomy group (p = .65). At median follow-up, disease-free survival (DFS) and overall survival (OS) in the laparoscopy group and laparotomy group were 87.4% versus 91.6% and 82.7% versus 86.5%, respectively. Cause-specific survival (CSS) was 90.5% in the laparoscopy group versus 94.9% in the laparotomy group. In patients with International Federation of Gynecology and Obstetrics stage I, DFS was 91.2% in the laparoscopy group versus 93.8% in the laparotomy group, OS was 86.5% versus 89.7%, and CSS was 93.4% versus 95.9%. CONCLUSION: Laparoscopic vaginal treatment of patients with endometrial cancer provides a survival outcome comparable with laparotomy. If these data are confirmed, laparoscopic procedures should be included in routine therapy for patients with endometrial cancer.

Analysis of morbidity in patients with endometrial cancer: is there a commitment to offer laparoscopy?

OBJECTIVE: Benefits of laparoscopy over laparotomy in patients with endometrial cancer (EC) are well known. As many patients with EC carry co-morbid conditions, surgery is exposing them to increased risk of complications. A review of the patients with EC recruited so far in a clinical trial comparing laparoscopy to laparotomy was performed. The goal was to identify patients carrying specific risk factors for complications, who would most benefit of laparoscopy and be the ideal candidates for this surgical approach. PATIENTS AND METHODS: Between July 1995 and December 2002, 122 patients with uterine cancer entered the study. Sixty-three patients were allocated to the laparoscopy (LPS) arm (group A), while 59 were allocated to the laparotomy (LPT) arm (group B). Rate and type of intra-, early and late post-operative complications were prospectively recorded. Risk factors for complications are analyzed to define a group of patients truly benefiting from laparoscopy. RESULTS: Overall, 12 patients out of 122 (9.8%) have experienced intra-operative, 43 patients out of 122 (35.2%) early post-operative and 25 patients out of 122 (20.4%) late post-operative complications. Rate of intra-operative complications was 4.7% in group A (3 patients out of 63) vs. 15.2% in group B (9 patients out of 59), P = 0.082. Early post-operative complications rate was 23.8% in group A (15 out of 63) and 47.4% in group B (28 out of 59), P = 0.011. Rate of late post-operative complications was 7.9% (5 out of 63) in group A vs. 35.5% (21 out of 59), P = 0.001. Univariate analysis shows co-morbid medical conditions, weight >80 kg, Quetelet index >30 and age >65 years to be predictive of complications and, in fact, a subgroup of patients presenting with these characteristics (n = 57, 30 in group A and 27 in group B) has been recognized to accumulate 60% of the overall complications. In these patients, multivariate analysis identifies the surgical technique (LPS vs. LPT) to be the only significant risk factor for complications. CONCLUSION: At least one third of the patients with EC carry serious co-morbidities with an increased surgical risk for complications. For this subgroup of patients, a laparoscopic-vaginal approach significantly reduces the rate of complications and should be the standard of surgical treatment.