Management after initial surgery of nonfunctioning pituitary adenoma: surveillance, radiotherapy or surgery?

INTRODUCTION: The first line of treatment for nonfunctioning pituitary adenoma (NFPA) is surgery. Adjuvant radiotherapy or surveillance and new treatment (second surgical operation or salvage radiotherapy) in case of recurrence are options discussed at the multidisciplinary tumor board. The purpose of this study was to evaluate the therapeutic outcome for each option. METHODS: The records of 256 patients followed with NFPA between 2007 and 2018 were retrospectively reviewed. Mean age at initial surgery was 55 years [18-86]. Post-operative MRI found a residual tumor in 87% of patients. Mean follow-up was 12.1 years [0.8-42.7]. RESULTS: After initial surgery, 40 patients had adjuvant radiotherapy. At 5, 10 and 15 years progression-free survival (PFS) was significantly different after surgery alone (77%, 58% and 40%) compared to surgery and adjuvant radiotherapy (84%, 78% and 78%) (HR = 0.24 [0-0.53] p < 0.0005). Overall, after first, second or third surgical operation, 69 patients had adjuvant radiotherapy and 41 salvage radiotherapy. Five-year PFS was similar for adjuvant (90%) and salvage radiotherapy (97%) (p = 0.62). After a second surgical operation, 62% and 71% of patients were irradiated after 2 and 5 years respectively. The risk of corticotropic and thyrotropic deficiency rates were 38% and 59% after second or third surgical operation and 40% and 73% after radiotherapy. Brain tumors occurred in 4 patients: 1 meningioma present at initial surgery, and after radiotherapy, 1 neurinoma which appeared at 5 years, 1 glioblastoma at 13 years and 1 meningioma at 20 years. CONCLUSION: Among patients treated by surgery for NFPA, a "wait-and-see" attitude should be an option since adjuvant radiotherapy is not superior to salvage radiotherapy. However, in case of recurrence or progression, the authors recommended delivery of salvage radiotherapy to avoid a second surgical operation.

Neoadjuvant treatment for borderline resectable pancreatic adenocarcinoma is associated with higher R0 rate compared to upfront surgery.

BACKGROUND: Neoadjuvant treatment (NAT) is debated for borderline resectable pancreatic cancer (BRPC). This retrospective study assessed the impact of NAT on R0 rate and survival for BRPC patients in comparison with upfront surgery (US). MATERIAL AND METHODS: Between 2010 and 2017 patient records for all consecutive patients treated for BRPC according to NCCN 2017 were reviewed. The endpoints analysed were R0 rate, recurrence-free-survival (RFS) and overall survival (OS). RESULTS: Seventy-nine patients were included: 63 (79.7%) patients received NAT and 16 (20.3%) were upfront operated. NAT consisted in FOLFIRINOX (median cycles: 5, range 4-8) followed by chemoradiation (n = 55, 87.3%, median dose: 54 Gy). Thirty-nine (61.9%) patients had resection. R0 rate was higher in the NAT group considering a margin clearance of 0 mm (94.9%) or 1 mm (89.7%) compared to the US group (68.8% and 43.8% respectively). In the whole population, median RFS was 12.6 [95%CI: 10.5-22.1] in the NAT group vs 7.7 [95%CI: 4.4-14] months in the US group (p < 0.01). Median OS was 29.0 [95%CI: 23.5-63.1] and 27.2 [95%CI: 11.6-38.8] months in the NAT and US groups respectively (p = 0.06). In operated patients the NAT group achieved better RFS and OS than the US group (p < 0.01 for both). In multivariate analysis NAT, surgical resection and age <65 (p < 0.01 for both) were prognostic of RFS. NAT, surgical resection and adjuvant chemotherapy were prognostic of OS (p < 0.05 for all). In operated patients (n = 55) multivariate analysis showed that N1 status was associated with decreased RFS; age < 65 and NAT were associated with a longer RFS. Receiving a NAT, an adjuvant chemotherapy and achieving a ypT0-1N0 status were associated with better OS. NAT was well tolerated with 14.3% grade ≥ 3 toxicities. CONCLUSION: NAT permitted a high R0 rate with a 0- or 1-mm clearance margin and was associated with better RFS and OS for patients with BRPC.

Interval between planning and frameless stereotactic radiosurgery for brain metastases: are our margins still accurate?

BACKGROUND: Advances in intracranial stereotactic radiosurgery (SRS) have led to dramatically reduced planning target volume (PTV) margins. However, tumor growth between planning and treatment may lead to treatment failure. Our purpose was to assess the kinetics of tumor growth before SRS for brain metastases. METHODS: This retrospective, monocentric study included all consecutive patients (pts) treated for brain metastases secondary to melanoma (ML) and non-small cell lung cancer (NSCLC) between June 2015 and May 2016. All pts underwent diagnostic brain imaging and a radiosurgery planning MRI, during which gross tumor volume (GTV) was delineated. Linear and exponential models were used to extrapolate a theoretical GTV at first day of treatment, and theoretical time to outgrow the PTV margins. RESULTS: Twenty-three ML and 31 NSCLC brain metastases (42 pts, 84 brain imaging scans) were analyzed. Comparison of GTV at diagnosis and planning showed increased tumor volume for 20 ML pts (96%) and 22 NSCLC pts (71%). The shortest time to outgrow a 1 mm margin was 6 days and 3 days for ML and 14 and 8 days for NSCLC with linear and exponential models, respectively. CONCLUSIONS: Physicians should bear in mind the interval between SRS planning and treatment. A mathematical model could screen rapidly progressing tumors.

Modified Gluteal Fold V-Y Advancement Flap for Reconstruction After Radical Vulvectomy.

OBJECTIVE: To describe the surgical technique of the V-Y cutaneous supra-fascial (modified) gluteal advancement flaps for reconstruction after radical vulvectomy and to assess the outcome of patients according to their clinical characteristics. METHODS: Between January 2006 and July 2012, 36 V-Y flaps were performed in 21 patients to cover the defect after radical surgery of primary vulvar cancers. Surgery duration, blood loss, hospital stay, and wound healing were assessed according to patient age, body mass index (BMI), American Society of Anesthesiologists (ASA) score, and the initial defect size. RESULTS: Median patient age, BMI, and ASA score were 80 (range, 31-91), 28 (range, 18-36), 3 (range, 1-3), respectively. Median surgery duration and blood loss were 180 minutes (range, 60-275) and 400 mL (range, 100-1000), respectively. Median operating time was higher in patients ASA3 than ASA less than 3, 200 versus 120 minutes (P = 0.038). Median initial defect size was higher in patients with BMI greater than 28 than 28 or less, 92 versus 55 cm (P = 0.004). Local scar defect was observed in 16 patients (76%), mild, less than 10 cm in 10 patients. Median wound healing duration was higher in patients with bilateral than unilateral flap, 16 versus 9.5 days (P = 0.034). CONCLUSIONS: The V-Y cutaneous suprafascial gluteal advancement flap for vulvar reconstruction after vulvectomy is an easy, safe, and reliable procedure. However, even mild local scar defect after bilateral flap may impact on wound healing and hospital stay, in elderly and ASA3 patients.

Use of FDG-PET to guide dose prescription heterogeneity in stereotactic body radiation therapy for lung cancers with volumetric modulated arc therapy: a feasibility study.

BACKGROUND: The aim of this study was to assess if FDG-PET could guide dose prescription heterogeneity and decrease arbitrary location of hotspots in SBRT. METHODS: For three patients with stage I lung cancer, a CT-simulation and a FDG-PET were registered to define respectively the PTVCT and the biological target volume (BTV). Two plans involving volumetric modulated arc therapy (VMAT) and simultaneous integrated boost (SIB) were calculated. The first plan delivered 4 × 12 Gy within the PTV(CT) and the second plan, with SIB, 4 × 12 Gy and 13.8 Gy (115% of the prescribed dose) within the PTV(CT) and the BTV respectively. The Dmax-PTV(CT) had to be inferior to 60 Gy (125% of the prescribed dose). Plans were evaluated through the D95%, D99% and Dmax-PTV(CT), the D2 cm, the R50% and R100% and the dice similarity coefficient (DSC) between the isodose 115% and BTV. DSC allows verifying the location of the 115% isodose (ideal value = 1). RESULTS: The mean PTV(CT) and BTV were 36.7 (±12.5) and 6.5 (±2.2) cm3 respectively. Both plans led to similar target coverage, same doses to the OARs and equivalent fall-off of the dose outside the PTV(CT). On the other hand, the location of hotspots, evaluated through the DSC, was improved for the SIB plans with a mean DSC of 0.31 and 0.45 for the first and the second plans respectively. CONCLUSIONS: Use of PET to decrease arbitrary location of hotspots is feasible with VMAT and SIB for lung cancer.

[Delays in the diagnosis and treatment of lung cancer for patients treated with radiation therapy]. / Délais de prise en charge initiale des patients atteints de cancer bronchique traités en radiothérapie.

OBJECTIVE: To describe delays in diagnosis and treatment of lung cancer in patients treated by radiotherapy from the first abnormal imaging to the first day of treatment. PATIENTS AND METHODS: Our retrospective single-center study included all patients treated for primary lung cancer in our center receiving radiotherapy alone or in association to chemotherapy or surgery, between 1st May and 15th September 2011. RESULTS: We included 40 patients. Mean age was 65.3 years and sex ratio was 4 (32 males). In 72.5% (n = 29) of the cases, the objective of the treatment was palliative. Median delay between the first abnormal imaging to the first day of treatment was 75.5 days (CI 95% [63.6-134.4]). Median diagnostic delay to obtain a pathological proof was 38 days (CI 95% [27.9-100]). Median therapeutic delay to start treatment was 31 days (CI 95% [24.6-38.5]). When considering radiotherapy, median delay between multidisciplinary staff decision and first radiotherapy session was 26 days (CI 95% [22.4-33.3]). CONCLUSION: The study of the delays in diagnosis and treatment is the first step to reduce them. Detailed analysis helps to propose some measures to improve these delays.

Survival and prognosis of women with invasive cervical cancer according to age.

OBJECTIVES: We assessed survival and compared clinical and pathological prognostic factors of women with invasive cervical cancer according to the age in order to define a cutoff point where screening should become useless. METHODS: The survival of 308 women with invasive cervical cancer treated at Bordeaux University Hospital between 1976 and 1996 was evaluated on December 31, 2000. Kaplan-Meier survival curves calculated with regard to age were compared by the log-rank test. Prognostic factors were assessed according to age (cutoff 65 years) and included in a Cox model. Survival of women in our population within a particular age group was compared to survival of women of the same age range, using indirect standardization. RESULTS: The 5-year survival rate of women under 65 (n = 221), between 65 and 74 (n = 56), and over 75 (n = 31) was 75%, 69%, 42%, respectively (P < 0.001). Compared to women under 65, women over 65 had a significantly lower Karnofsky performance status and a significantly more advanced clinical stage cancer involving vaginal bleeding. Age, gross cervical appearance, clinical vaginal involvement, histologic grade, and microscopic cervical and parametrial involvements were independent prognostic factors. Compared to women under 65, the risk of mortality was 1.3, 95% CI = 0.8-2.7, P = 0.189, for women aged 65-74, and 2.3, 95% CI = 1.1-3.9, P = 0.022, for women over 75. Mortality of women with invasive cervical cancer was significantly higher than that of women in the general population in the indirect standardization model (SMR = 1.9, 95% CI = 1.5-2.2), except beyond age 75. CONCLUSIONS: Age was a significant prognostic factor in our study and advanced stages were significantly increased after 65. However, survival after 75 was not different from that of the population. These considerations address the question of the maintenance of screening between 65 and 75.