Clinical outcome in children and adolescents with Hodgkin lymphoma after treatment with chemotherapy alone - the results of the United Kingdom HD3 national cohort trial

Purpose

To assess the efficacy of a standardised hybrid chemotherapy treatment programme for Hodgkin lymphoma (HL) in a national series of children and adolescents.

Patients and methods

The 381 assessable patients, treated between March 2000 and April 2005 in the United Kingdom Children’s Cancer Study Group trial, were reviewed to evaluate overall survival (OS), disease free survival (DFS) and deaths. Protocol treatment for stages 2-4 offered a hybrid programme of ChlVbPP (chlorambucil, vinblastine, prednisolone, procarbazine) alternating with ABVcD (doxorubicin, bleomycin, vincristine, dacarbazine). Patients with stage I disease only were offered involved field radiation alone or hybrid chemotherapy.

Results

With a median follow up of 5.1 years (range 0.5-8.4 years), the 5 years OS and DFS for all patients was 97% and 78%, respectively. By multivariate analysis, mediastinal and stage IV disease at presentation were the only factors that affected achieving a complete response. The 5-year DFS rate for patients with stage IV disease was 55% whilst patients with mediastinal disease had a 2-fold higher risk of an event.

Conclusions

This study demonstrated that multi-agent chemotherapy alone is insufficient treatment for patients with mediastinal and stage IV disease.     

Laryngeal Cancer Treatment and Survival Differences across Regional Cancer Centres in Ontario, Canada

Aims

We conducted a population-based study of practice patterns and outcome across the regional cancer centres providing care to patients with laryngeal cancer in the Province of Ontario, Canada.

Materials and methods

: This was a retrospective cohort study of 1547 patients with cancers of the glottic or supraglottic larynx diagnosed between 1982 and 1995. Data were collected via chart review, including: patient and disease characteristics, treatment, waiting times and treatment volumes. Vital status was obtained from the Ontario Cancer Registry. Variations across the nine regional cancer centres are described and their effect on outcome explored. All analyses were stratified by stage I and II separately from stage III and IV.

Results

Treatments differed across centres (P < 0.0001); for instance, in the stage I and II group, use of a daily dose of >2.54 Gy varied from 0 to 87.6% and in the stage III and IV group, total laryngectomy rates varied from a low of 6% to a high of 53%. The percentage of patients waiting more than 6 weeks from diagnosis to first treatment varied from 17 to 49% (P < 0.0001). Multivariate analysis revealed cause-specific survival differences that were not explained by control for case mix, treatment or waiting times. Differences ranged from an 82% risk reduction in one centre compared with the reference (stage I and II group, P = 0.008) to a 153% increase in risk (stage III and IV group, P = 0.02). Centre case volumes were not associated with cause-specific survival.

Conclusions

This study quantifies the degree of variation that can occur in the treatment and outcome of people with cancer. We cannot properly assess whether care delivery is of high quality until we have a better understanding of the factors that drive such variations.     

Intra-operative pubic arch interference during prostate seed brachytherapy in patients with CT-based pubic arch interference of ?1 cm

Purpose

There are only a few reports on the frequency of intra-operative pubic arch interference (I-PAI) during prostate seed brachytherapy (PB).

Materials and methods

Two hundred and forty-three patients with a CT-based pubic arch interference (PAI) of ?1 cm and a prostate volume of ?50-60 cc underwent PB. Those patients requiring needle repositioning by ?0.5 cm on the template were scored as having I-PAI. The incidence of I-PAI and its impact on biochemical control were analyzed.

Results

Intra-operative PAI was encountered in 47 (19.3%) patients. Forty two patients (17.3%) had I-PAI in 1-2 needles, two (0.8%) had I-PAI in four needles and three patients (1.2%) had I-PAI in six needles. Overall, 1.4% of needles required repositioning due to I-PAI. BMI > 27 kg/m² and wider (>75 mm) pubic bone separation at mid ramus (PS-ML) were associated with a lower incidence of I-PAI. At a median follow-up of 50.1 months, the 3- and 5-year bPFS was 97.3% and 95.2%, respectively. The 5-year bPFS rates for patients with and without I-PAI were 95.6% and 95%, respectively (p = 0.28).

Conclusions

The use of CT-based PAI of ?1 cm as a selection criterion for PB is a simple and reliable method for minimizing the incidence of I-PAI and maintaining excellent biochemical control rates.     

Adjuvant radioimmunotherapy after radiofrequency ablation of colorectal liver metastases in an experimental model

Purpose

Radiofrequency ablation (RFA) has shown to improve survival in patients not eligible for surgical resection of colorectal liver metastases. However, recurrences after RFA are a major problem. Adjuvant radioimmunotherapy (RIT) after surgical resection of liver metastases has shown to improve survival. The aim of the present study was to test the hypothesis that adjuvant RIT might be an effective way to prevent recurrent liver metastases after RFA in an experimental model.

Methods

Tumours in the liver were induced by intrahepatic injection of 300 000 CC531 cells in male Wag/Rij rats (n = 60). Ten days later, the intrahepatic tumours were treated with RFA. Adjuvant RIT (¹⁷⁷Lu-labelled monoclonal antibody MG1 at 300 MBq/kg) was administered intravenously either at the day of RFA (day 10) or 7 days later. Control rats received no treatment. Primary endpoint was survival.

Results

Administration of ¹⁷⁷Lu-MG1 resulted in a transient decrease in body weight, compared to no adjuvant treatment. However, no other signs of clinical discomfort were registered. Log rank test showed that the survival curves of the groups treated with RIT, either at day 10 or day 17, did not differ significantly from the survival curve of the rats that did not receive adjuvant treatment (P = 0.902).

Conclusion

This study shows that adjuvant RIT does not increase survival after RFA of colorectal liver metastases in rats.     

Effect of negative lymph node count on survival for gastric cancer after curative distal gastrectomy

Aims

The aim of this study is to evaluate the long-term effect of negative lymph node (LN) counts on the prognosis after curative distal gastrectomy among gastric cancer patients.

Methods

The study enrolled 634 patients with gastric cancer, who had undergone curative resection (R0) with distal gastrectomy from 1995 to 2004. Long-term surgical outcomes and relationships between the negative LN count and the 5-year survival rate were investigated.

Results

The 5-year survival rate of the entire cohort was 57.6%. The number of metastasis negative LN was positively associated with the retrieved node according to the Pearson’s correlation test (P < 0.001). Cox regression analysis showed the negative LN count was an independent predictor of survival (P < 0.05). Based on the statistical assumption the best fitting linear, linear regression showed a significant survival improvement based on increasing negative LN count for patients with stages I (P = 0.014), II (P = 0.011) and III (P = 0.003). The greatest survival differences were observed at cutoff value 10 negative LN counts for stage I, and 15 for stages II, III and IV.

Conclusion

Negative LN counts can reflect the extent of lymphadenectomy for gastric cancer after curative distal gastrectomy. The higher the negative LN count, the better the survival would be; the best long-term survival outcome was observed on the negative LN count more than 10 (stage I) or 15 (stages II, III, and IV).     

Patients’ needs and preferences in routine follow-up for early breast cancer; an evaluation of the changing role of the nurse practitioner

Background

In evaluating follow-up of early breast cancer, patients’ views on care are important. The aim of this study was to evaluate the effect of the introduction of nurse practitioners (NPs) in a breast cancer unit on patients’ informational needs, preferences and attitude towards follow-up.

Patients and methods

A cross-sectional survey was performed among two groups in 2005. Group A (n = 89) consisted of patients operated before, and group B (n = 100) after the introduction of a breast cancer unit (respectively in 1998-1999 and 2001-2004).

Results

Response was 72% in group A and 84% in group B. Median follow-up was 69 (54-86) and 33 (0-57) months, respectively. Aspects highly appreciated by patients in both groups were lifetime follow-up, information about prognosis, life style and additional investigations. Important discussion subjects were fatigue, pain, genetic factors, prevention and arm function/lymph-oedema. Less valued aspects were information about peers, conversations with psychologists or social workers, breast reconstruction, and acceptation by family members. The informational needs and preferences did not differ statistically significantly between both groups. In group B, communication with the caregiver was valued higher and more patients indicated that the caregiver took the time needed. More patients in group B indicated that follow-up could be performed by the NP. Duration of follow-up correlated with preferred frequency, not with informational needs in follow-up, only young age increased these needs.

Conclusion

Despite the limitations of this retrospective study, we conclude that while expectations and informational needs did not change with the introduction of a NP to the standard care, patient satisfaction increased and communication and time taken were appreciated more.     

Intrapleural administration of lipoplatin in an animal model

Background

Lipoplatin is a new liposomal cisplatin already tested in solid tumors with encouraging results. Little is known about the activity of lipoplatin administered intrapleurally (IP).

Aim

The aim of this study was to assess in an animal model the pharmacokinetics, and potentially induced histopathological lesions of lung and kidney after IP vs. IV injection of lipoplatin.

Methods

15 male Wistar rats were assigned to an IV group at dose 10 mg/kg of lipoplatin (group 1) and to IP groups at 10 (group 2) or 20 mg/kg (group 3) equal to 60 and 120 mg/m² in humans respectively. After lipoplatin administration, serial plasma samples were analyzed by atomic absorption spectrometry for the maximum plasma concentration (C_max), the area under the plasma concentration-time curve (AUC), and the total body clearance (CL). Pleura, lungs and kidneys of the rats were histologically examined for possible lesions.

Results

The C_max was significantly higher in groups 1 vs. 2 (p = 0.02) and vs. 3 (p = 0.01). The AUC of groups 3 vs. 1 was significantly higher (p = 0.028) but the AUC of groups 2 vs. 1 was significantly lower (p = 0.02). CL in IP rats did not differ considerably compared to the IV. Inflammatory changes were noted in the pleura of IP rats and mild kidneys lesions in IV group.

Conclusion

Compared to the IV route, IP20 administration of lipoplatin yielded higher AUC, equal CL, but a significantly lower C_max. As C_max is a determinant of lipoplatin toxicity, IP administration might offer a more effective therapeutic index while improving tolerability. We noted fibrotic changes in the pleura of IP rats, and mild kidneys changes in IV rats, as expected.     

Applicator reconstruction in MRI 3D image-based dose planning of brachytherapy for cervical cancer

Background and purpose

To elaborate a method for applicator reconstruction for MRI-based brachytherapy for cervical cancer.

Materials and methods

Custom-made plastic catheters with a copper sulphate solution were made for insertion in the source channels of MR-CT compatible applicators: plastic and titanium tandem ring applicators, and titanium needles. The applicators were CT and MR scanned in a phantom for accurate 3D assessment of applicator visibility and geometry. A reconstruction method was developed and evaluated in 19 patient MR examinations with ring applicator (plastic: 14, titanium: 5). MR applicator reconstruction uncertainties related to inter-observer variation were evaluated.

Results

The catheters were visible in the plastic applicator on T1-weighted images in phantom and in 14/14 clinical applications. On T2-weighted images, the catheters appeared weaker but still visible in phantom and in 13/14 MR clinical applications. In the titanium applicator, the catheters could not be separated from the artifacts from the applicator itself. However, these artifacts could be used to localize both titanium ring applicator (5/5 clinical applications) and needles (6/6 clinical applications). Standard deviations of inter-observer differences were below 2 mm in all directions.

Conclusion

3D applicator reconstruction based on MR imaging could be performed for plastic and titanium applicators. Plastic applicators proved well to be suited for MRI-based reconstruction. For improved practicability of titanium applicator reconstruction, development of MR applicator markers is essential. Reconstruction of titanium applicator and needles at 1.5 T MR requires geometric evaluations in phantoms before using the applicator in patients.     

Oncological outcomes in patients undergoing radical nephrectomy and vena cava thrombectomy for renal cell carcinoma with venous extension: A single-centre experience

Objective

To report on the effectiveness of the surgical management of renal cell carcinoma (RCC) in patients with a neoplastic thrombus of the vena cava.

Patients and methods

We examined pre- and post-operative clinical data for all patients who had received a nephrectomy for the management of RCC with a neoplastic thrombus of the vena cava between spanning 10 years. The procedure depended on the exact location and size of the thrombus according to the Mayo Clinic and the 2009 TNM classifications.

Results

A total of 32 patients underwent surgery. Eight of these patients had stage I, nine had stage II, six had stage III and nine had stage IV thrombi according to the Mayo Clinic staging, and twenty were T3b, eight were T3c and four were T4 according to the 2009 TNM classifications. An open abdominal approach was performed in patients with stage I and II thrombi, whereas five of the stage III patients and all of the stage IV patients required combined sternotomies. Five patients whose thrombi extended to the right atrium were treated with a cardiac bypass. The complication rate was 53% and the peri-operative mortality rate was 12.5%. The median follow-up interval was 64 months. The overall and cancer-specific five-year survival rates for all stages combined were 47% and 52%, respectively.

Conclusion

Surgical resection remains the first-line treatment for patients with RCC infiltrating the vena cava, but surgical morbidity is prevalent and survival is poor.     

Carboplatin chemotherapy in patients with recurrent high-grade glioma

Aims

To investigate the efficacy of carboplatin chemotherapy in patients with recurrent high-grade glioma (HGG) who had received at least two previous lines of chemotherapy.

Materials and methods

Case notes of patients who had received chemotherapy with carboplatin for recurrent HGG between June 2005 and July 2008 were reviewed. Baseline characteristics and outcomes after treatment were recorded.

Results

Twenty-six patients received carboplatin as third- or fourth-line chemotherapy for recurrent HGG (grade III glioma n = 8; grade IV glioma n = 18). The median number of cycles completed was 2.5. The most common reasons for discontinuing treatment were progressive disease and death (n = 19; 73%). Three patients (12%) had a partial response, five (19%) had stable disease and 18 (69%) had progressive disease. Six month progression-free survival was 23% (25% in patients with grade III glioma and 22% in patients with grade IV glioma). The median time to disease progression from the first treatment with carboplatin was 9.0 weeks. The median survival was 19.4 weeks (27.9 weeks for patients with grade III glioma and 8.1 weeks for patients with grade IV glioma). Among patients with either stable disease or a partial response, the median survival was 42.4 weeks compared with 11.7 weeks in patients with progressive disease (hazard ratio for death with progressive disease on treatment: 5.02; 95% confidence interval 1.64-15.4; P = 0.005). Carboplatin was well tolerated overall.

Conclusions

Single-agent carboplatin has modest activity in patients with recurrent HGG who have received at least two lines of chemotherapy. The overall time to progression is short and over two-thirds of patients had to discontinue treatment due to progressive disease. Among the small proportion of patients achieving stable disease or a partial response to treatment, the median survival is improved. More effective but well tolerated regimens are required for this patient population.     

Quadrimodal treatment of high-risk T1 and T2 bladder cancer: Transurethral tumor resection followed by concurrent radiochemotherapy and regional deep hyperthermia

Background and purpose

To assess the safety and effectiveness of treating high-risk T1 and T2 bladder cancer with transurethral resection (TUR-BT) followed by radiochemotherapy (RCT) combined with regional deep hyperthermia (RHT).

Material and methods

Between 2003 and 2007, 45 patients were enrolled. After TUR-BT patients received radiotherapy (RT) of the bladder and regional lymph nodes with 50.4 Gy, and a boost to the bladder of 5.4-9 Gy. RCT was applied to 43/45 patients. RHT was administered once weekly. Response was re-evaluated 6 weeks after RT by restaging-TUR. Toxicity was graded with the CTCAE, version 3.0. QoL was evaluated by a dedicated questionnaire.

Results

The median follow-up was 34 months (range 12-60). The median number of hyperthermia treatments was 5 (range 1-7). Acute toxicity grades 3 and 4 occurred in 20% (9/45) and 9% (4/45), respectively. Late toxicity grades 3/4 were seen in 24% (11/45). Complete response rate was 96% (43/45). Local recurrence-free survival was 85%, overall survival was 80%, disease-specific survival was 88%, metastasis-free survival was 89%, and the bladder-preserving rate was 96% (43/45) at 3 years. Eighty percent (24/30) were at least mostly satisfied with their bladder function.

Conclusions

The quadrimodal treatment was feasible and well tolerated. Local control and bladder-preserving rates were encouraging.     

Comparison of diaphragmatic surgery at primary or interval debulking in advanced ovarian carcinoma: an analysis of 163 patients

Aims of the study and methods

Survival, complications and recurrences after diaphragmatic surgery at primary or interval debulking surgery were compared. One hundred and sixty three consecutive patients with stage III/IV ovarian cancer underwent diaphragmatic surgery between September 1993 and December 2007. Primary debulking was performed in group 1 (89) patients and interval debulking was performed in group 2 (74) patients. Cytoreductive outcome, overall survival (OS), disease-free survival (DFS) and post-operative complications were analysed.

Results

Despite differences in baseline mean age (p = 0.015), in FIGO stage III/IV (p = 0.036) and in mean largest diameter of metastatic disease at the beginning of debulking surgery (p = 0.037), the optimal debulking rates (residual tumour less than 1 cm) were similar (p = 0.065). Excision of diaphragmatic metastases was most frequently performed in group 1 (77.53%) and coagulation was most frequently performed in group 2 (58.10%). Similar overall survival and disease-free survival rates were found. After the propensity matching procedure, the largest diameter of metastatic disease at the time of debulking and no residual tumour (complete debulking) were demonstrated as independent prognostic factors for OS. Plaque-like lesions on the diaphragm metastases were significantly (p = 0.015) more associated with diaphragm recurrence than papillary lesions. Minor and major complications related to diaphragmatic surgery as well as mean operating time, post-operative care in intensive care unit and length of hospitalisation were significantly higher in group 1 rather than in group 2 (p = 0.043).

Conclusions

Diaphragmatic dissemination resulted in similar survival and cytoreductive rates after primary and interval debulking. However, the morbidity was less after interval debulking as fewer surgical procedures were performed.     

Survival after trimodality therapy for malignant pleural mesothelioma: Radical Pleurectomy, chemotherapy with Cisplatin/Pemetrexed and radiotherapy

Introduction

The role of surgery in the management of malignant pleural mesothelioma (MPM) is controversial and there are no established guidelines. We describe the feasibility and long-term outcomes associated with Radical Pleurectomy (RP) as surgical therapy modality in a standardized trimodality therapy concept of MPM.

Methods

From November 2002 to October 2007, 35 out of 102 consecutive patients with MPM were enrolled in our prospective database. They underwent trimodality therapy, including RP followed by 4 cycles of chemotherapy with Cisplatin (75 mg/m²)/Pemetrexed (500 mg/m²) and radiotherapy 4-6 weeks after operation.

Results

Median age was 65 years. Nineteen patients were in advanced stages III and IV (54.3%). Tumor histology was epithelial in 27 patients (77.1%). Macroscopic complete resection could be achieved in 18 patients (51.4%). Surgical morbidity/mortality and trimodality treatment-related mortality were 20.0%, 2.9% and 5.8%, respectively. Thirty-three patients completed the trimodality therapy. Median follow-up was 21.7 months. Overall median survival was 30.0 months. One-, 2-, and 3-year-survival were 69%, 50% and 31%, respectively. Advanced stages III/IV (p = 0.06), macroscopic incomplete resections (p = 0.001), non-epithelial histology (p = 0.55) and nodal metastases (p = 0.19) were associated with poorer survival.

Conclusions

The trimodality therapy concept with RP demonstrates promising results in terms of long-term survival, morbidity and mortality. We propose that a surgical philosophy of limiting the procedure related morbidity while achieving comparable cytoreductive results allows patients to maintain physiological reserve to be eligible for multimodality treatment options in the long-term. The observed and theoretical benefits of this trimodality treatment approach warrant confirmation in larger RCT.     

Mesothelin and kidney function--analysis of relationship and implications for mesothelioma screening

Purpose

Malignant mesothelioma (MM) carries a poor prognosis and remains a major public health issue in many countries. Outcomes may be improved with earlier detection and this justifies screening the at-risk asbestos-exposed population. Soluble mesothelin is a potential biomarker for MM, but it has been observed to be elevated in patients with reduced kidney function. Defining the relationship between mesothelin concentrations and kidney function will allow more accurate interpretation of this assay.

Materials and methods

A cross-sectional study consisting of 144 patients with chronic kidney disease (CKD) was conducted at Sir Charles Gairdner Hospital and Royal Perth Hospital in Western Australia. Only patients with CKD stages II-V were recruited while those with a history of renal transplant, dialysis, or malignancy were excluded. Serum and urine mesothelin and creatinine concentrations were determined.

Results

There were 33, 49, 31 and 31 patients in CKD stages II, III, IV and V, respectively recruited. Serum mesothelin increased significantly with increasing serum creatinine (p < 0.0001), and worsening stage of CKD (p < 0.0001). A significant correlation between urine mesothelin to creatinine ratio and serum mesothelin concentration was detected (p = 0.002). No significant difference was found in urine mesothelin to creatinine ratios across the four CKD stage groups.

Conclusion

Serum mesothelin concentration is elevated in individuals with renal impairment. Renal function should therefore be taken into account during interpretation of this assay.     

Breast radiotherapy as part of loco-regional treatments in stage IV breast cancer patients with oligometastatic disease

Background

Local treatments seem to improve metastasis progression-free survival (MPFS) and overall survival (OS) when added to systemic therapies in stage IV breast cancer.

Methods

From 1990 to 2003, we reviewed 9138 cases treated and registered in the Institut Gustave-Roussy breast cancer database. Among them, 308 had presented with stage IV disease. Eighty percent of patients (n = 239) had received a loco-regional treatment and they were categorized into two groups: loco-regional radiotherapy (LRRT) alone (Group 1; n = 147) or breast and axillary surgery ± LRRT (Group 2; n = 92).

Results

The median follow-up was 6.5 years. LRRT obtained a long-standing loco-regional clinical response in 85% of patients. The 3-year MPFS rates were 20% in Group 1 and 39% in Group 2; the 3-year OS rates were 39% and 57%, respectively. However, no significant differences in MPFS or OS were observed between the two groups when adjusted on prognostic factors.

Conclusions

Radiation therapy alone provides long-standing local control and yields MPFS and OS rates equivalent to those obtained when radiation therapy is combined with surgery, whatever the prognostic factors. Loco-regional therapies, especially radiation therapy alone, may have an important role to play in the treatment of selected patients with stage IV breast cancer.     

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.     

Expression of cysteine-rich 61 is correlated with poor prognosis in patients with esophageal squamous cell carcinoma

Introduction

Cysteine-rich 61 (Cyr61), a secreted protein belonged to the CCN family, was involved in the progression of many cancers. The purpose of this study was to explore the clinical significance of Cyr61 expression in esophageal squamous cell carcinoma (ESCC).

Materials and methods

Cyr61 expression was detected on tissue microarrays of ESCC samples in 372 cases by using immunohistochemical staining. Survival analysis was assessed by the Kaplan-Meier analysis. Relative risk was evaluated by the multivariate Cox proportional hazards model.

Results

The staining pattern of Cyr61 was heterogeneous and varied from negative to intense expression in a cytoplasmic distribution. Kaplan-Meier analysis revealed that expression of Cyr61 was related to poor survival of ESCC patients (P = 0.001). Further analysis revealed that Cyr61 high-expression was related to poorer overall survival of patients in stage I/II (P = 0.001); but did not effect the overall survival of patients in stage III/IV. Univariate and multivariate analysis suggested that Cyr61 expression status was an independent prognostic factor for ESCC (P = 0.001).

Discussion

Cyr61 might play important roles in the progression of ESCC. Cyr61 is a new biomarker to predict the prognosis of ESCC patients.     

Impact of the prophylactic gastrostomy for unresectable squamous cell head and neck carcinomas treated with radio-chemotherapy on quality of life: Prospective randomized trial

Background and purpose

Concomitant radio-chemotherapy is the gold standard treatment for unresectable head and neck carcinomas. Placement of prophylactic gastrostomy has been proposed to provide adequate nutrition during the therapeutic sequence. The objectives of this study were to assess the impact of prophylactic gastrostomy on the 6-month quality of life, and to determine the factors related to this quality of life.

Materials and methods

Design. randomized, controlled, open study (“systematic percutaneous gastrostomy” versus “no systematic gastrostomy”). Patients. squamous cell head and neck carcinoma (stages III and IV, UICC 1997). Setting. oncological departments of French university teaching hospitals. Treatment. optimal concomitant radio-chemotherapy. Evaluations. T0 baseline evaluation, T1 during the treatment, T2 end of the treatment, and T3 6-month post-inclusion. Primary endpoint. 6-month quality of life (Qol) assessed using SF36, EORTC QLQ-C30, EORTC QLQ H&N35 questionnaires.

Results

The Qol changes from baseline included a decline (T1 and T2) followed by an improvement (T3). Qol at 6 months was significantly higher in the group receiving systematic prophylactic gastrostomy (p = 10⁻³). Higher initial BMI and lower initial Karnofsky index were significant factors related to a higher 6-month Qol.

Conclusions

The study results suggest that prophylactic gastrostomy improves post-treatment quality of life for unresectable head and neck cancer patients, after adjusting for other potential predictive quality of life factors.     

A randomised trial of endobronchial ultrasound guided sampling in peripheral lung lesions

Aim

The aim of the study was to evaluate endobronchial ultrasound (EBUS) for peripheral lung lesions and to find the most cost effective combination of sampling techniques.

Materials

264 patients with lesions suspicious of malignancy were recruited in Bergen and Aalesund, Norway from 2005 to 2008.

Methods

The study was a prospective randomised cohort study. EBUS was performed with a 1.7 mm rotating probe. X-ray fluoroscopy was used in both arms. The different sampling techniques were evaluated in a cost-effectiveness analysis.

Results

The detection rate for cancer was 36% in the EBUS group, 44% in the non-EBUS group (ns). Lesions below 3 cm and lesions assumed difficult to reach had significant lower detection rates in the EBUS group. Lesions visualised by EBUS had a higher detection rate for cancer than lesions not visualised by EBUS (62% vs. 19%, p < 0.01). The cost of one additional positive sample was 1211 euro when brushing was added to biopsy. It was not cost effective to add washing or TBNA.

Conclusion

EBUS did not increase the detection rate for cancer in peripheral lung lesions when bronchoscopy was performed by bronchoscopists at all levels of expertise. Biopsy and brushing was the most cost effective combination of sampling techniques.     

Can we optimize chemo-radiation and surgery in locally advanced stage III non-small cell lung cancer based on evidence from randomized clinical trials? A hypothesis-generating study

Purpose

Improved local tumor control (LC) improves survival of patients with non-small cell lung cancer (NSCLC). We estimated the capability of surgical and non-surgical options to improve LC further in this disease.

Methods

Eligible studies were phase III trials reporting 2-year survival data as well as the incidence of LC and/or distant metastases. Effect estimates, as well as the statistical uncertainty of these, were combined in order to estimate the benefit in terms of LC from combining multiple modalities.

Results

It was estimated that the highest rates of LC can be obtained with high-dose concurrent chemo-radiation followed by surgery. In this situation, escalating the pre-operative radiation dose from 45 to 66 Gy, delivered concurrently with chemotherapy, could increase LC from 58% to 76%. Toxicity may also be higher, but could not be estimated. Without surgery, the gain in LC from concurrent chemo-radiation versus sequential, corresponds to a radiation dose increase from 65 to 72 Gy.

Conclusions

We hypothesize that high-dose concurrent chemo-radiation followed by surgery could be superior to other current treatment approaches for selected patients with stage III NSCLC, provided toxicity would be low. At present, high-dose concurrent chemo-radiation followed by surgery should be considered experimental.