Adjuvant chemoradiation versus surgery alone for adenocarcinoma of the ampulla of Vater

Background and purpose

To examine the role of adjuvant chemoradiation (CRT) in patients with resected ampullary adenocarcinoma.

Materials and methods

The records of patients who underwent curative surgery for ampullary adenocarcinoma at a single institution between 1992 and 2007 were reviewed. Final analysis included 111 patients, 45% of which also received adjuvant CRT.

Results

Median overall survival (OS) was 36.2 months for all patients. Adverse prognostic factors for OS included T stage (T3/4 vs. T1/T2, p = 0.046), node status (positive vs. negative, p < 0.001), and histological grade (grade 3 vs. 1/2, p = 0.09). Patients receiving CRT were more likely to have advanced T-stage (p = 0.001), node positivity (p < 0.001), and poor histologic grade (p = 0.015). Patients who received CRT were also significantly younger (p = 0.001). On univariate analysis, adjuvant CRT failed to result in a significant difference in survival when compared to surgery alone (median OS: 33.4 vs. 36.2 months, p = 0.969). Patients with node-positive resections who underwent CRT had a non-significant improvement in survival (median OS: 21.6 vs. 13.0 months, p = 0.092). Thirty-three percent of patients developed distant metastasis. Common sites of distant metastasis included liver (23%) and peritoneum (7%).

Conclusions

Adjuvant chemoradiation following curative resection for ampullary adenocarcinoma did not lead to a statistically significant benefit in overall survival. A significant proportion of patients still developed distant metastatic disease suggesting a need for more effective systemic adjuvant therapy.     

Image-guided intensity-modulated radiotherapy (IG-IMRT) for biliary adenocarcinomas: Initial clinical results

Purpose

Biliary tract lesions are comparatively rare neoplasms, with ambiguous indications for radiotherapy. The specific aim of this study was to report the clinical results of a single-institution biliary tract series treated with modern radiotherapeutic techniques, and detail results using both conventional and image-guided intensity-modulated radiation therapy (IG-IMRT).

Methods and materials

From 2001 to 2005, 24 patients with primary adenocarcinoma of the biliary tract (gallbladder and extrahepatic bile ducts) were treated by IG-IMRT. To compare outcomes, data from a sequential series of 24 patients treated between 1995 and 2005 with conventional radiotherapy (CRT) techniques were collected as a comparator set. Demographic and treatment parameters were collected. Endpoints analyzed included treatment-related acute toxicity and survival.

Results

Median estimated survival for all patients completing treatment was 13.9 months. A statistically significant higher mean dose was given to patients receiving IG-IMRT compared to CRT, 59 vs. 48 Gy. IG-IMRT and CRT cohorts had a median survival of 17.6 and 9.0 months, respectively. Surgical resection was associated with improved survival. Two patients (4%) experienced an RTOG acute toxicity score > 2. The most commonly reported GI toxicities (?RTOG Grade 2) were nausea or diarrhea requiring oral medication, experienced by 46% of patients.

Conclusion

This series presents the first clinical outcomes of biliary tract cancers treated with IG-IMRT. In comparison to a cohort of patients treated by conventional radiation techniques, IG-IMRT was feasible for biliary tract tumors, warranting further investigation in prospective clinical trials.     

Gemcitabine in the chemoradiotherapy for locally advanced pancreatic cancer: A meta-analysis

Aims

Whether gemcitabine based chemoradiotherapy (GEM-based CRT) is superior to 5-fluorouracil based chemoradiotherapy (5-FU-based CRT) for locally advanced pancreatic cancer (LAPC) remains uncertain. The aim of the present study was to evaluate the effect of GEM-based CRT compared with 5-FU-based CRT.

Methods

Electronic database including Medline, Embase, Cochrane controlled trials register, PubMed (update to December 2010) and manual bibliography searches were carried out. A meta-analysis of all randomized clinical trials (RCTs) or other comparative studies comparing GEM-based CRT and 5-FU-based CRT were performed.

Results

Three RCTs and one retrospective comparative study including 229 patients were assessed. Meta-analysis showed survival advantage of GEM-based CRT compared with 5-FU-based CRT for 12-month (12-mo) survival rates (SRs) (RR = 1.54, 95% CI 1.05-2.26, p = 0.03). Moreover, there were also trends of benefit for SR after 6-months (RR 1.13, 95% CI 0.98-1.30, p = 0.09) and 24-months (24-mo: RR 2.41, 95% CI 0.90-6.48, p = 0.08), though the trends did not reach statistical significance. More frequent severe acute hematologic toxicities were found in the GEM-based CRT group.

Conclusions

The meta-analysis found that GEM-based CRT was better than 5-FU-based CRT in the treatment of LAPC, especially for 12-mo SRs. However, the acute toxicity should be carefully regarded.     

Short-course radiotherapy, with elective delay prior to surgery, in patients with unresectable rectal cancer who have poor performance status or significant co-morbidity

Background and purpose

Standard treatment for rectal cancer which threatens the expected plane of resection on MRI imaging is long-course, pre-operative chemoradiotherapy (1.8-2 Gy, 25-28 fractions). Not all patients are suitable for this because of age, poor performance status or co-morbidities. We describe our experience of short-course (5 × 5 Gy) pre-operative radiotherapy with planned, delayed surgery (SCPRT-delay) in this patient group.

Materials and methods

Between April 2001 and October 2007, 43 patients were selected for SCPRT-delay. The clinical records were retrospectively evaluated.

Results

Median age was 82 (range 58-87). Forty-one patients had radiotherapy of which 26 (61%) were subsequently able to have surgery. Of these, R0, R1 and R2 resections were performed in 22, 2 and 2 patients, respectively. Treatment was well tolerated, although two patients required hospital admission for management of diarrhoea and one developed significant late small bowel toxicity, attributable to radiotherapy. In those undergoing R0 or R1 resection there have been no local recurrences (median follow-up 18 months). Median survival for the whole group was 23 months, although this was 44 months in those undergoing surgery.

Conclusions

SCPRT-delay appears to be a useful alternative to long-course pre-operative chemoradiotherapy in this high-risk group of patients.     

Is concurrent radiation therapy required in patients receiving preoperative chemotherapy for adenocarcinoma of the oesophagus? A randomised phase II trial

Introduction

Preoperative chemotherapy (CT) and preoperative chemoradiation therapy (CRT) for resectable oesophageal cancer have been shown to improve overall survival in meta-analyses. There are limited data comparing these preoperative therapies. We report the outcomes of a randomised phase II trial comparing preoperative CT and CRT for resectable adenocarcinoma of the oesophagus and gastro-oesophageal junction.

Methods

Patients were randomised to receive preoperative CT with cisplatin (80 mg/m²) and infusional 5 fluorouracil (1000 mg/m²/d) on days 1 and 21, or preoperative CRT with the same drugs accompanied by concurrent radiation therapy commencing on day 21 of chemotherapy and the 5 fluorouracil reduced to 800 mg/m²/d. The radiation dose was 35 Gy in 15 fractions over 3 weeks. The endpoints were toxicity, response rates, resection (R) status, progression-free survival (PFS), overall survival (OS) and quality of life.

Results

Seventy-five patients were enroled on the study: 36 received preoperative CT and 39 preoperative CRT. Toxicity was similar for CT and CRT. Eight patients (11%) did not proceed to resection. The histopathological response rate (CRT 31% versus CT 8%, p = 0.01) and R1 resection rate (CRT 0% versus CT 11%, p = 0.04) favoured those receiving CRT. The median PFS was 14 and 26 months for CT and CRT respectively (p = 0.37). The median OS was 29 months for CT compared with 32 months for CRT (p = 0.83).

Conclusions

Despite no difference in survival, the improvement from preoperative CRT with respect to margin involvement makes this treatment a reasonable option for bulky, locally advanced resectable adenocarcinoma of the oesophagus.     

Elective nodal irradiation (ENI) in definitive chemoradiotherapy (CRT) for squamous cell carcinoma of the thoracic esophagus

Background and purpose

There are some reports indicating that prophylactic three-field lymph node dissection for esophageal cancer can lead to improved survival. But the benefit of ENI in CRT for thoracic esophageal cancer remains controversial. The purpose of the present study is to retrospectively evaluate the efficacy of elective nodal irradiation (ENI) in definitive chemoradiotherapy (CRT) for thoracic esophageal cancer.

Materials and methods

Patients with squamous cell carcinoma (SCC) of the thoracic esophagus newly diagnosed between February 1999 and April 2001 in our institution was recruited from our database. Definitive chemoradiotherapy consisted of two cycles of cisplatin/5FU repeated every 5 weeks, with concurrent radiation therapy of 60 Gy in 30 fractions. Up to 40 Gy radiation therapy was delivered to the cervical, periesophageal, mediastinal and perigastric lymph nodes as ENI.

Results

One hundred two patients were included in this analysis, and their characteristics were as follows: median age, 65 years; male/female, 85/17; T1/T2/T3/T4, 16/11/61/14; N0/N1, 48/54; M0/M1, 84/18. The median follow-up period for the surviving patients was 41 months. Sixty patients achieved complete response (CR). After achieving CR, only one (1.0%; 95% CI, 0-5.3%) patient experienced elective nodal failure without any other site of recurrence.

Conclusion

In CRT for esophageal SCC, ENI is effective for preventing regional nodal failure. Further evaluation of whether ENI leads to an improved overall survival is needed.     

Preoperative radiotherapy and local excision of rectal cancer with immediate radical re-operation for poor responders

Background and purpose

To report an early analysis of prospective study exploring preoperative radiotherapy and local excision in rectal cancer.

Materials and methods

Mucosa at tumour edges was tattooed. Patients with cT1-3N0 tumour <3-4 cm were treated with either 5 × 5 Gy + 4 Gy boost (N = 31) or chemoradiation (50.4 Gy + 5.4 Gy boost, 1.8 Gy per fraction + 5-fluorouracyl and leucovorin; N = 13). Thirteen patients from the short-course group were unfit for chemotherapy. The interval from radiation to full-thickness local excision was 6 weeks. The protocol called for conversion to a transabdominal surgery in case of ypT2-3 disease or positive margin.

Results

The postoperative complications requiring hospitalization were recorded in 9% of patients. The rate of pathological complete response was 41%. The rate of patients requiring conversion was 34%; however, 18% actually underwent conversion and the remaining 16% refused or were unfit. During the 14 months of median follow-up, local recurrence was detected in 7% of patients and all underwent salvage surgery. Of 19 patients in whom initially anterior resection was likely, 16% had abdominoperineal resection performed for a conversion or as a rescue procedure.

Conclusion

Our study suggests that the short-course radiation prior to local excision is a treatment option for high-risk patients.     

End of life care in adolescents and young adults with cancer: experience of the adolescent unit of the Institut Gustave Roussy

Background

Cancer is the third leading cause of death in adolescents and young adults (AYA). Little is known, however, about how end-of-life unfolds for those who die of progressive disease. In order to better evaluate the specific needs of these patients, we performed this study providing baseline information about end-of-life care patterns for AYA in our department.

Patients

A standardised form was used to collect data concerning all 45 patients treated for a malignancy in the Paediatric and Adolescent Oncology Department at the Gustave Roussy Institute, and who had died of progressive disease above 13 years of age, over a two-year period.

Results

The main diagnoses were sarcomas and brain tumours. Previous cancer-directed treatment included a median of 3 different chemotherapy regimens, high-dose chemotherapy with haematopoietic stem cell support for 13% and radiotherapy for 40%. One in every four patients had been enrolled in a clinical trial at diagnosis. Median survival was 18 months after the diagnosis and 7 months after the first relapse/progression. During the last week of life, the median number of physical symptoms was 4, mostly pain and dyspnoea. Frequent psychological symptoms were sadness, anxiety, fear and guilt. End-of-life care included transfusions, artificial nutrition, corticosteroids, pain control, sedation but also palliative chemotherapy. The median time spent in hospital during the last month of life was 16 days. Most patients had died in hospital.

Conclusions

The terminally ill adolescent displays notable challenges to care providers and requires a holistic approach with the help of a multidisciplinary team.     

Concurrent high-dose radiotherapy with low-dose chemotherapy in patients with non-small cell lung cancer of the superior sulcus

Background and purpose

In the treatment of patients with tumours of the sulcus superior (SST), achieving local control is essential because residual or recurrent disease is associated with severe locoregional problems. This study evaluates the efficacy of concurrent daily low-dose cisplatin (6 mg/m²) and high-dose radiotherapy (66 Gy) followed by surgical resection in selected patients.

Material and methods

Clinical charts, imaging and pathology reports were retrospectively reviewed. Survival was analysed using the Kaplan-Meier method.

Results

Forty-nine patients with stage II/III SST were treated with concurrent high-dose radiotherapy and low-dose chemotherapy (CRT). Mean follow-up was 49 months (range 2-152).Nineteen patients underwent additional resection after CRT. In 53% a pathological complete response (pCR) was observed (10/19pts). Acute severe toxicity occurred in 49% (9/19pts). Late severe toxicity occurred in 3 patients. The 2- and 5-year overall survival was 74% and 33%, respectively. Local tumour control was 100%. Thirty patients received CRT only. Acute severe toxicity occurred in 23% (7/30pts). Treatment-related mortality was 2%. The 2- and 5-year overall survival was 31% and 18%, respectively. Locoregional disease-free survival was 48% at 5 years.

Conclusions

Concurrent high-dose (66 Gy) radiotherapy and daily low-dose cisplatin was associated with a high pCR rate. Excellent local control was achieved after additional resection in selected patients. However, the occurrence of severe toxicity in long-term survivors after concurrent chemoradiation followed by surgery must be considered.     

Retreatment with erlotinib: Regain of TKI sensitivity following a drug holiday for patients with NSCLC who initially responded to EGFR-TKI treatment

Background

Tyrosine kinase inhibitors (TKI) of the epidermal growth factor receptor (EGFR) are approved as treatment of non-small-cell lung cancer (NSCLC). Despite an initially impressive response to EGFR-TKIs, patients with an activating EGFR mutation invariably relapse. For these patients few treatment options are available after additional progression during or after chemotherapy. The aim of this study is to examine the effect of retreatment with an EGFR-TKI after a drug holiday.

Patients and methods

We retrospectively reviewed the medical records of 14 patients with stage IV NSCLC who progressed after long-term disease control with EGFR-TKI, who were subsequently treated with standard chemotherapy and at renewed progression retreated with EGFR-TKI.

Results

Fourteen patients (five male, nine female, median age 55 years (39-70 years) received retreatment with erlotinib. The median interval from the discontinuation of EGFR-TKI to the 2nd episode was 9.5 months (3-36 months). Before starting retreatment 36% (n = 5) had a T790M mutation. Retreatment resulted in 36% (n = 5) partial response, 50% stable disease (n = 7) and 14% progressive disease (n = 2). Among patients with a T790M mutation this number was two, one and two, respectively. Seven patients are still on therapy without signs of progression. Median follow up is 9 months (1.5-16+ months) and median PFS is 6.5 months (1-16+ months).

Conclusion

Our findings suggest that retreatment with erlotinib is an option for patients with NSCLC who initially benefited from previous EGFR-TKI treatment and progressed after standard cytotoxic chemotherapy.     

Prognostic effect of stromal lymphocyte infiltration in thymic carcinoma

Background

The purpose of this study was to clarify the relationship between the tumor infiltrating lymphocytes and clinical outcome in patients with thymic carcinoma.

Methods

Tissue specimens from 32 patients who underwent surgical resection for thymic carcinoma were immunohistochemically analyzed for CD4, CD8 and CD20 expression.

Results

Tumor-infiltrating lymphocytes were generally more abundant in the stroma. The patients with low CD4+ lymphocytes (p = 0.037) and low CD20+ lymphocytes (p = 0.045) within tumor stroma showed poor survival. Furthermore, concurrent low levels of CD4+ and CD20+ (p = 0.014), CD8+ and CD20+ (p = 0.025), and, CD4+, CD8+, and CD20+ (p = 0.025) in tumor stroma were significantly associated with poor prognosis when compared to the others group.

Conclusion

Our results indicate that infiltrating CD4+, CD8+, and CD20+ lymphocytes in cancer stroma may cooperate to suppress cancer progression and their presence together appear to be prognostic factor in thymic carcinoma.     

Factors influencing outcome in patients undergoing portal vein resection for adenocarcinoma of the pancreas

Background

Survival rates after surgery and adjuvant chemotherapy for pancreatic ductal adenocarcinoma (PDA) remain low. Selected patients with portal/superior mesenteric vein (PV) involvement undergo PV resection at pancreaticoduodenectomy (PD). This study analyses outcomes for PD with/without PV resection in patients with PDA.

Methods

A retrospective analysis of prospectively collected data on patients requiring PD for histologically proven adenocarcinoma between 1/1997 and 9/2009 identified 326 patients with PDA, with 51 requiring PD with PV resection. Patients were analyzed in two groups: PD + PV resection vs. PD alone. Multivariate analysis was used to identify predictive variables influencing survival and the Kaplan-Meier method to estimate patient survival.

Results

Mean age for patients with PV resection was 66.4 (range 46-80) years, 47% were male. Both groups had similar patient demographics, perioperative and tumor characteristics. Postoperative morbidity was similar for patients with and without PV resection (27.5 vs. 28.4%). 30-day mortality was significantly higher in patients with PV resection (13.7%) vs. PD alone (5.1%). Overall survival however was similar in both groups (median PD alone 14.8 months vs. 14.5 months PD + PV). Multivariate analysis identified age, tumor grading, stay on the ICU and lack of chemotherapy as independent risk factors for reduced long-term survival.

Conclusion

In carefully selected patients, PV resection results in similar long-term survival compared to PD alone. In selected patients, PV infiltration may be considered a sign of anatomical proximity of the tumor, rather than only a sign of increased tumor aggressiveness.     

Significance of an exon 2 G4C14-to-A4T14 polymorphism in the p73 gene on survival in rectal cancer patients with or without preoperative radiotherapy

Background and purpose

An exon 2 G4C14 → A4T14 polymorphism in the p73 gene was shown to be related to survival in several types of cancers, including colorectal cancer. The purpose was to investigate if this polymorphism was related to survival in rectal cancer patients with or without preoperative radiotherapy.

Materials and methods

DNA extracted from tissue of 138 rectal cancer patients that received preoperative radiotherapy or had surgery alone was typed for the polymorphism by PCR using confronting two-pair primers.

Results

Among patients, 69% had GC/GC genotype, 27% had GC/AT and 4% had AT/AT. In the radiotherapy group, patients carrying the AT (GC/AT + AT/AT) allele had stronger expression of p53 (p = 0.001) and survivin protein (p = 0.03) than those carrying the GC/GC genotype. Further, among patients receiving preoperative radiotherapy the GC/GC genotype tended to be related to better survival (p = 0.20). Patients with GC/GC genotype, along with negative p53 and weak survivin expression showed better survival than the other patients (p = 0.03), even after adjusting for TNM stage and tumor differentiation (p = 0.01, RR, 7.63, 95% CI, 1.50-38.74). In the non-radiotherapy group, the polymorphism was not related to survival (p = 0.74).

Conclusions

Results suggest that the p73 G4C14 → A4T14 polymorphism could be one factor influencing outcome of preoperative radiotherapy in rectal cancer patients.     

Influence of body mass index on outcome in advanced colorectal cancer patients receiving chemotherapy with or without targeted therapy

Purpose

Obesity is associated with an increased risk of development and recurrence of colorectal cancer. However, the role of obesity in advanced colorectal cancer (ACC) patients is unknown. We investigated the effect of body mass index (BMI) on overall survival (OS) in ACC patients receiving systemic treatment in two large phase III studies (CAIRO and CAIRO2).

Patients and methods

Treatment data were obtained and analysed from 796 ACC patients who were treated with chemotherapy in the CAIRO study, and from 730 ACC patients who were treated with chemotherapy plus targeted therapy in the CAIRO2 study. Baseline height and weight were used to assign patients to one of the following BMI categories: A (<18.5 kg/m²), B (18.5-24.9 kg/m²), C (25.0-29.9 kg/m²) and D (?30.0 kg/m²).

Results

In 796 patients of the CAIRO study a high BMI was associated with better median OS (8.0, 14.9, 18.4 and 19.5 months for BMI categories A, B, C, and D, respectively; P = 0.001), and was an independent prognostic factor for OS in a multivariate analysis. BMI was not associated with OS in 730 patients who participated in the CAIRO2 study, although a trend was observed.

Conclusions

These results show that BMI is an independent prognostic factor for survival in patients receiving chemotherapy, but not in patients receiving chemotherapy and targeted therapy. The possible decreased efficacy of bevacizumab in obese patients may explain this discrepant result. The role of BMI in patients receiving targeted therapy should be further tested.     

Induction chemotherapy with cisplatin and epirubicin followed by radiotherapy and concurrent cisplatin in locally advanced nasopharyngeal carcinoma observed in a non-endemic population

Background and purpose

Chemoradiotherapy (CRT) represents the main therapy choice in the treatment of locoregionally advanced nasopharyngeal carcinoma (NPC). The aim of this study was the clinical evaluation of neoadjuvant chemotherapy (NACT) followed by CRT in a non-endemic population affected by advanced NPC.

Materials and methods

Patients with locoregionally advanced NPC were treated with three cycles of induction chemotherapy (CHT) with cisplatin (100 mg/m²) plus epirubicin (90 mg/m²), followed by cisplatin (100 mg/m²) and concomitant radiotherapy (70 Gy).

Results

In 40 patients treated with such protocol, after the completion of induction CHT and CRT we observed the objective response rates of 90% and 100%, respectively. Treatment tolerability and toxicity were easily controllable. With a median follow-up time of 54 months, 3- and 5-year disease-free survival was 75% and 65% and 3- and 5-year overall survival was 84% and 77%.Three- and 5-year locoregional control was 82% and 70%, and 5-year distant metastases free survival was 75%.

Conclusions

NACT with cisplatin and epirubicin followed by concomitant CRT represents a feasible, efficient treatment for patients with advanced NPC. This regimen ensures an excellent locoregional disease control and overall survival with a low incidence of distant metastases.     

ACTN4 copy number increase as a predictive biomarker for chemoradiotherapy of locally advanced pancreatic cancer

Background:

Several clinical trials have compared chemotherapy alone and chemoradiotherapy (CRT) for locally advanced pancreatic cancer (LAPC) treatment. However, predictive biomarkers for optimal therapy of LAPC remain to be identified.We retrospectively estimated amplification of the ACTN4 gene to determine its usefulness as a predictive biomarker for LAPC.

Methods:

The copy number of ACTN4 in 91 biopsy specimens of LAPC before treatment was evaluated using fluorescence in situ hybridisation (FISH).

Results:

There were no statistically significant differences in overall survival (OS) or progression-free survival (PFS) of LAPC between patients treated with chemotherapy alone or with CRT. In a subgroup analysis of patients treated with CRT, patients with a copy number increase (CNI) of ACTN4 had a worse prognosis of OS than those with a normal copy number (NCN) of ACTN4 (P=0.0005, log-rank test). However, OS in the subgroup treated with chemotherapy alone was not significantly different between patients with a CNI and a NCN of ACTN4. In the patients with a NCN of ACTN4, the median survival time of PFS in CRT-treated patients was longer than that of patients treated with chemotherapy alone (P=0.049).

Conclusions:

The copy number of ACTN4 is a predictive biomarker for CRT of LAPC.     

Phase II trial of Uracil/Tegafur plus leucovorin and celecoxib combined with radiotherapy in locally advanced pancreatic cancer

Background and purpose

To investigate the efficacy and toxicity of a short intensive Uracil/Tegafur (UFT) based chemoradiotherapy scheme combined with celecoxib in locally advanced pancreatic cancer.

Material and methods

The Academic Medical Centre, Amsterdam and the Erasmus Medical Centre, Rotterdam enrolled 83 eligible patients with unresectable pancreatic cancer in a prospective multicentre phase II study. Median age was 62 years, median tumour size 40 mm and the majority of the patients (85%) had pancreatic head cancers. Treatment consisted of 20 × 2.5 Gy radiotherapy combined with UFT 300 mg/m² per day, leucovorin (folinic acid) 30 mg and celecoxib 800 mg for 28 days concomitant with radiotherapy. Four patients were lost to follow-up.

Results

Full treatment compliance was achieved in 55% of patients, 80% received at least 3 weeks of treatment. No partial or complete response was observed. Median survival was 10.6 months and median time to progression 6.9 months. Toxicity was substantial with 28% grades III and IV gastro-intestinal toxicity and two early toxic deaths.

Conclusions

Based on the lack of response, the substantial toxicity of mainly gastro-intestinal origin and the reported mediocre overall and progression free survival, we cannot advise our short intensive chemoradiotherapy schedule combined with celecoxib as the standard treatment.     

Intrafraction motion in patients with cervical cancer: The benefit of soft tissue registration using MRI

Background and purpose

During radiation delivery, target volumes change their position and shape due to intrafraction motion. The extent of these changes and the capability to correct for them will contribute to the benefit of an MRI-accelerator in terms of PTV margin reduction. Therefore, we investigated the primary CTV motion within a typical IMRT delivery time for cervical cancer patients for various correction techniques: no registration, rigid bony anatomy registration, and rigid soft tissue registration.

Materials and methods

Twenty-two patients underwent 2-3 offline MRI exams before and during their radiation treatment. Each MRI exam included four sagittal and four axial MRI scans alternately within 16 min. We addressed the CTV motion by comparing subsequent midsagittal CTV delineations and investigated the correlation with intrafraction bladder filling.

Results

The maximum (residual) motions within 16 min for all points on the CTV contour for 90% of the MRI exams without registration, with rigid bony anatomy registration, and with rigid soft tissue registration were 10.6, 9.9, and 4.0 mm. A significant but weak correlation was found between intrafraction bladder filling and CTV motion.

Conclusions

Considerable intrafraction CTV motion is observed in cervical cancer patients. Intrafraction MRI-guided soft tissue registration using an MRI-accelerator will correct for this motion.     

Phase 2 trial of linifanib (ABT-869) in patients with advanced renal cell cancer after sunitinib failure

Purpose

This study assessed the efficacy and safety of linifanib in patients with advanced renal cell carcinoma (RCC) who were previously treated with sunitinib.

Materials and methods

This open-label, multicentre, phase 2 trial of oral linifanib 0.25 mg/kg/day enrolled patients who had prior nephrectomy and adequate organ function. The primary end-point was objective response rate (ORR) per response evaluation criteria in solid tumors (RECIST) by central imaging. Secondary end-points were progression-free survival (PFS), overall survival (OS) and time to progression (TTP). Safety was also assessed.

Results

Fifty-three patients, median age 61 years (range 40-80) were enrolled (August 2007 to October 2008) across 12 North-American centres. Median number of prior therapies was 2 (range 1-4); 43 patients (81%) had clear-cell histology. ORR was 13.2%, median PFS was 5.4 months (95% Confidence Interval (CI): 3.6, 6.0) and TTP was the same; median OS was 14.5 months (95% CI: 10.8, 24.1). The most common treatment-related adverse events (AEs) were diarrhoea (74%), fatigue (74%) and hypertension (66%), and the most common treatment-related Grade 3/4 AE was hypertension (40%).

Conclusions

Linifanib demonstrated clinically meaningful activity in patients with advanced RCC after sunitinib failure. At 0.25 mg/kg/day, significant dose modifications were required. An alternative, fixed-dosing strategy is being evaluated in other trials.