Association of urethral toxicity with dose exposure in combined high-dose-rate brachytherapy and intensity-modulated radiation therapy in intermediate- and high-risk prostate cancer

Introduction

To report acute and late toxicities in patients with intermediate- and high-risk prostate cancer treated with combined high-dose-rate brachytherapy (HDR-B) and intensity-modulated radiation therapy (IMRT).

Materials and methods

From March 2003 to September 2005, 64 men were treated with a single implant HDR-B with 21 Gy given in three fractions, followed by 50 Gy IMRT along with organ tracking. Median age was 66.1 years, and risk of recurrence was intermediate in 47% of the patients or high in 53% of the patients. Androgen deprivation therapy was received by 69% of the patients. Toxicity was scored according to the CTCAE version 3.0. Median follow-up was 3.1 years.

Results

Acute grade 3 genitourinary (GU) toxicity was observed in 7.8% of the patients, and late grades 3 and 4 GU toxicity was observed in 10.9% and 1.6% of the patients. Acute grade 3 gastrointestinal (GI) toxicity was experienced by 1.6% of the patients, and late grade 3 GI toxicity was absent. The urethral V₁₂₀ (urethral volume receiving ?120% of the prescribed HDR-B dose) was associated with acute (P = .047) and late ? grade 2 GU toxicities (P = .049).

Conclusions

Late grades 3 and 4 GU toxicity occurred in 10.9% and 1.6% of the patients after HDR-B followed by IMRT in association with the irradiated urethral volume. The impact of V₁₂₀ on GU toxicity should be validated in further studies.     

Toxicity after reirradiation of pulmonary tumours with stereotactic body radiotherapy

Purpose

To assess toxicity and feasibility of reirradiation with stereotactic body radiotherapy (SBRT) after prior lung SBRT for primary lung cancer or lung metastases.

Patients and materials

Twenty-nine patients reirradiated with SBRT on 32 lung lesions (11 central, 21 peripheral) were retrospectively reviewed. Median follow-up time was 12 months (range 1-97). The primary endpoint was toxicity, secondary endpoints were local control and overall survival time. Toxicity was scored according to the NCI-CTCAE version 3.

Results

Grade 3-4 toxicity was scored 14 times in eight patients. Three patients died because of massive bleeding (grade 5). Larger clinical target volumes (CTV) and central tumour localization were associated with more severe toxicity. There was no correlation between mean lung dose (MLD) and lung toxicity. Local control at 5 months after reirradiation was 52%, as assessed by CT-scan (n = 12) or X-thorax (n = 3). A larger CTV was associated with poorer local control. Kaplan-Meier estimated 1- and 2-year survival rates were 59% and 43%, respectively.

Conclusions

Reirradiation with SBRT is feasible although increased risk of toxicity was reported in centrally located tumours. Further research is warranted for more accurate selection of patients suitable for reirradiation with SBRT.     

Correlation of Currently Used Radiobiological Parameters with Local Control and Acute and Late Mucosal Toxicity in Randomised Studies of Altered Fractionation for Locally Advanced Head and Neck Cancer

Aims

There has been a resurgence in interest in radiobiological modelling in head and neck cancer. The aim of this study was to determine if currently used parameters accurately predict both tumour and toxicity outcomes.

Materials and methods

Trials were identified from a recent meta-analysis of altered fractionation. The tumour biologically effective dose (tBED; α/β = 10 Gy, t_k [onset time of accelerated repopulation] = 22 days, t_p [average doubling time during accelerated repopulation] = 3 days, α = 0.3 Gy⁻¹), acute mucosal biologically effective dose (amBED; α/β = 10 Gy, t_k = 7 days, t_p = 2.5 days, α = 0.3 Gy⁻¹) and late mucosal biologically effective dose (lmBED; α/β = 3 Gy) were calculated for each arm of each trial. The correlation between the absolute percentage difference in BED between treatment arms and the observed percentage difference in local control, acute grade 3 mucositis and late grade 3 mucosal reaction was then assessed.

Results

A strong correlation was observed between the percentage difference in tBED and the percentage difference in local control (P = 0.006). A trend towards a correlation was seen between the percentage difference in amBED and the percentage difference in acute grade 3 mucositis (P = 0.06). A significant correlation was observed between the percentage difference in lmBED and the percentage difference in grade 3 late mucosal toxicity (P = 0.02). However, a 15% decrease in lmBED between control and experimental arms of the study was necessary for any sparing of late mucosal toxicity to be observed.

Conclusions

Currently used parameters for tumour accurately predict outcomes in randomised trials of altered fractionation. Although the relationship may be more complex for late mucosal reaction, the presence of a correlation is noteworthy given the infrequent reporting or occurrence of this toxicity. In the future, radiobiological modelling with the addition of volumetric parameters will be highly relevant, given attempts to dose escalate with intensity-modulated radiotherapy in poor risk patients and de-escalate in patients with an excellent prognosis.     

Exhaled nitric oxide predicts radiation pneumonitis in esophageal and lung cancer patients receiving thoracic radiation

Background and purpose

Radiation pneumonitis is a significant toxicity following thoracic radiotherapy with no method to predict individual risk.

Materials and methods

Sixty-five patients receiving thoracic radiation for lung or esophageal cancer were enrolled in a phase II study. Each patient received respiratory surveys and exhaled nitric oxide measurements before, on the last day of, and 30-60 days after completing radiotherapy (RT). Pneumonitis toxicity was scored using the common terminology criteria for adverse events, version 4.0. The demographics, dosimetric factors, and nitric oxide ratio (NOR) of end RT/pre-RT were evaluated for correlation with symptomatic patients (Grade ?2).

Results

Fifty patients completed the trial. The pneumonitis toxicity score was: Grade 3 for 1 patient, Grade 2 for 6 patients, Grade 1 for 18 patients, and Grade 0 for 25 patients. Dosimetric factors were not predictive of symptoms. The NOR was 3.0 ± 1.8 (range 1.47-6.73) for the symptomatic and 0.78 ± 0.29 (range 0.33-1.37) for the asymptomatic patients (p = 0.006). A threshold NOR of 1.4 separated symptomatic and asymptomatic patients (p < 0.001). The average error was 4%.

Conclusions

Elevation in eNO on the last day of radiotherapy predicted subsequent symptomatic radiation pneumonitis weeks to months after treatment.     

Long-term results of full-dose gemcitabine with radiation therapy compared to 5-fluorouracil with radiation therapy for locally advanced pancreas cancer

Purpose

To retrospectively compare the efficacy and toxicity of full-dose gemcitabine based chemoradiotherapy (GemRT) versus 5-fluorouracil (5-FU) based chemoradiotherapy (5FURT) for locally advanced pancreas cancer (LAPC).

Methods

From January 1998 to December 2008, 93 patients with LAPC were treated either with 5FURT (n = 38) or GemRT (n = 55). 5FURT consisted of standard-field radiotherapy given concurrently with infusional 5-FU or capecitabine. GemRT consisted of involved-field radiotherapy given concurrently with full-dose gemcitabine (1000 mg/m² weekly) with or without erlotinib. The follow-up time was calculated from the time of diagnosis to the date of death or last contact.

Results

Patient characteristics were not significantly different between treatment groups. The overall survival (OS) was significantly better for GemRT compared to 5FURT (median 12.5 months versus 10.2 months; 51% versus 34% at 1 year; 12% versus 0% at 3 years; 7% versus 0% at 5 years, respectively; all P = 0.04). The OS benefit of GemRT was maintained on subset analysis without concurrent erlotinib or with sequential gemcitabine (all P < 0.05). The rates of distant metastasis, subsequent hospitalization, acute and late grade 3-5 gastrointestinal toxicities were not significantly different between the GemRT and 5FURT groups.

Conclusions

GemRT was associated with an improved OS compared to standard 5FURT. This approach yielded long-term survivors and was not associated with increased hospitalization or severe gastrointestinal toxicity.     

Predictors of acute bowel toxicity in patients treated with IMRT whole pelvis irradiation after prostatectomy

Purpose/objective

Whole pelvis irradiation with IMRT (WPRT-IMRT) after prostatectomy is efficient in reducing acute toxicity: however, a number of patients still experience moderate acute bowel toxicity.

Materials and methods

Ninety-six patients treated with WPRT-IMRT after prostatectomy with adjuvant or salvage intent were analysed. A number of parameters were individually recovered, including the DVHs of the intestinal cavity outside PTV and of the loops referred to both the WPRT phase and the whole treatment. Correlation between clinical-dosimetric parameters and acute bowel toxicity was investigated by logistic analyses. Best predictive cut-off values for continuous variables were assessed by ROC curves.

Results

15/96 (15.6%) Patients experienced grade 2 toxicity (no grade 3). Best dose-volume predictors were the fraction of loops receiving more than 45, 50 and 55 Gy (respectively, V45TL ? 50 cc, V50TL ? 13 cc, V55TL ? 3 cc; p-values ranging from 0.005 to 0.027). Age, GU acute toxicity, rectal acute toxicity and time between prostatectomy and IMRT were also predictors of acute bowel toxicity. Multivariate analysis showed that the most predictive independent parameters were age (OR: 1.13; 95%CI: 1.02-1.25; p = 0.021) and V50TL (?13 cc, OR: 8.2; 95%CI: 1.7-40; p = 0.009).

Conclusions

The risk of moderate acute uGI toxicity during WPRT-IMRT for post-operatively treated patients increases with age; the risk is substantially reduced in patients with small overlap between PTV and loops.     

Concomitant intensity modulated boost during whole breast hypofractionated radiotherapy - A feasibility and toxicity study

Background

Breast cancer sensitivity to large fraction size may be enhanced using hypofractionated concomitant boost radiotherapy (CBRT), thereby shortening overall treatment time. This ethics approved, prospective single cohort feasibility study was designed to evaluate the dosimetry and toxicity of CBRT using an intensity-modulated radiotherapy (IMRT) technique, compared with a standard sequential boost technique (SBT).

Methods

Fifteen women (11 right-sided; 4 left-sided) received 42.4 Gy to the whole breast and an additional 10.08 Gy to the tumor bed in 16 daily fractions, using IMRT and standard dose constraints. Each patient was replanned with the SBT, using mixed photon-electrons. Clinical target volume (CTV), dose evaluation volume (DEV), and organs at risk (OAR) dose distributions were compared with the SBT. Toxicity and treatment times were prospectively recorded.

Results

All 15 CBRT plans achieved the desired CTV (V_49.9Gy ? 99%) and DEV (V_49.9Gy ? 95%), coverage of the boost, compared with only 10 (66.7%, p = 0.03), and 12 (80%, p = 0.125) SBT plans, respectively. Ipsilateral lung (p < 0.0001), and heart (right-sided, p = 0.001; left-sided, p = 0.13) doses were lower. Grade 3 acute toxicity occurred in 1 (6.7%) patient. At 1 year, two (13.3%) additional patients had overall grade 2 late toxicity, compared with baseline. No grade 3-4 late toxicity was observed.

Conclusions

CBRT using IMRT improved boost coverage and lowered OAR doses, compared with SBT. Toxicities were acceptable using a daily boost of 3.28 Gy. While resource utilization was greater, overall treatment time was reduced.     

Predictive factors of gastroduodenal toxicity in cirrhotic patients after three-dimensional conformal radiotherapy for hepatocellular carcinoma

Background and purpose

To identify predictive factors for the development of gastroduodenal toxicity (GDT) in cirrhotic patients treated with three-dimensional conformal radiotherapy (3D-CRT) for hepatocellular carcinoma (HCC).

Materials and methods

We retrospectively analyzed dose-volume histograms (DVHs) and clinical records of 73 cirrhotic patients treated with 3D-CRT for HCC. The median radiation dose was 36 Gy (range, 30-54 Gy) with a daily dose of 3 Gy. The grade of GDT was defined by the Common Toxicity Criteria Version 2. The predictive factors of grade 3 GDT were identified.

Results

Grade 3 GDT was found in 9 patients. Patient’s age and the percentage of gastroduodenal volume receiving more than 35 Gy (V₃₅) significantly affected the development of grade 3 GDT. Patients over 50 years of age developed grade 3 GDT more frequently than patients under 50 years of age. The risk of grade 3 GDT grew exponentially as V₃₅ increased. The 1-year actuarial rate of grade 3 GDT in patients with V₃₅ < 5% is significantly lower than that in patients with a V₃₅ ?5% (4% vs. 48%, p < .01).

Conclusions

Patient’s age and V₃₅ were the most predictive factors for the development of grade 3 GDT in patients treated with RT.     

Trans-abdominal ultrasound (US) and magnetic resonance imaging (MRI) correlation for conformal intracavitary brachytherapy in carcinoma of the uterine cervix

Purpose

Trans-abdominal ultrasonography (US) is capable of determining size, shape, thickness, and diameter of uterus, cervix and disease at cervix or parametria. To assess the potential value of US for image-guided cervical cancer brachytherapy, we compared US-findings relevant for brachytherapy to the corresponding findings obtained from MR imaging.

Materials and methods

Twenty patients with biopsy proven cervical cancer undergoing definitive radiotherapy with/without concomitant Cisplatin chemotherapy and suitable for brachytherapy were invited to participate in this study. US and MR were performed in a similar reproducible patient positioning after intracavitary application. US mid-sagittal and axial image at the level of external cervical os was acquired. Reference points D1 to D9 and distances were identified with respect to central tandem and flange, to delineate cervix, central disease, and external surface of the uterus.

Results

Thirty-two applications using CT/MR compatible applicators were evaluable. The D1 and D3 reference distances which represent anterior surface had a strong correlation with R = 0.92 and 0.94 (p < 0.01). The D2 and D4 reference distances in contrast, which represent the posterior surface had a moderate (D2) and a strong (D4) correlation with R = 0.63 and 0.82 (p < 0.01). Of all, D2 reference distance showed the least correlation of MR and US. The D5 reference distance representing the fundal thickness from tandem tip had a correlation of 0.98. The reference distances for D6, D7, D8, and D9 had a correlation of 0.94, 0.82, 0.96, and 0.93, respectively.

Conclusions

Our study evaluating the use of US, suggests a reasonably strong correlation with MR in delineating uterus, cervix, and central disease for 3D conformal intracavitary brachytherapy planning.     

Stereotactic radiotherapy with real-time tumor tracking for non-small cell lung cancer: Clinical outcome

Purpose

To report the clinical outcome of treatment using real-time tumor tracking for 70 patients with inoperable stage I non-small cell lung cancer (NSCLC).

Materials and methods

Seventy inoperable patients with peripherally located early-stage NSCLC were treated with 45 or 60 Gy in three fractions using CyberKnife. Pathology was available in 51% of patients. Thirty-nine patients had a T1-tumor and 31 had a T2-tumor. Markers were placed using the vascular, percutaneous intra-, or extra-pulmonary approach, depending on the risk of pneumothorax.

Results

The actuarial 2-year local control rate for patients treated with 60 Gy was 96%, compared to 78% for patients treated with a total dose of 45 Gy (p = 0.197). All local recurrences (n = 4) occurred in patients with T2-tumors. Overall survival for the whole group at two years was 62% and the cause specific survival was 85%. The median follow-up was 15 months. Grade 3 toxicity occurred in two patients (3%) after marker placement. Treatment-related late grade 3 toxicity occurred in 7 patients (10%). No grade ?4 toxicity occurred.

Conclusion

Excellent local control of 96% at 1- and 2-years was achieved using 60 Gy in three fractions for NSCLC patients treated with the real-time tumor tracking. Toxicity was low.     

Feasibility of metronomic oral cyclophosphamide plus prednisolone in elderly patients with inoperable or metastatic soft tissue sarcoma

Background

The number of elderly people with soft tissue sarcoma (STS) is increasing. A sizeable population of elderly patients with STS is unfit for conventional doxorubicin- or ifosfamide-based chemotherapy. We assessed the feasibility of metronomic oral cyclophosphamide (CPM) in this population.

Patients and methods

Patients aged 65 years or older with unresectable STS received CPM 100 mg twice daily plus prednisolone 20 mg daily, the first week of a 2-week cycle in the outpatient setting. Main evaluation criterion was safety. Secondary evaluation criteria were objective response rate and progression-free survival.

Results

Twenty-six patients (median age: 72, range 66-88) received a total of 330 cycles (median per patient: 10, range 2-41) as first (n = 19) or second-line chemotherapy (n = 7). The most frequent histological subtypes were poorly differenciated sarcoma (n = 8), leiomyosarcoma and liposarcoma (n = 5 each) and angiosarcoma (n = 3). Grade ?3 lymphopenia was observed in 81% of pts but no opportunist infection occurred. Grade 3 anaemia and thrombocytopenia occurred in 2 pts (8%) each. No other grade 3-4 toxicity was seen. The response rate was 26.9% (95%CI: 9.9-44.0) and the disease control rate (responses and stable disease >12 weeks) was 69.2% (95%CI: 51.5-87.0). One complete (hepatic epithelioid haemangio-endothelioma) and 6 partial responses (including 5 pts with radiation-induced sarcomas) were seen. Progression-free survival ranged from 0 to 20.6 months (median: 6.8 months) and was significantly longer in patients with radiation-induced sarcomas (median: 7.8 versus 5.2 months, p = 0.02).

Conclusion

Metronomic CPM showed good safety results for this frail population, with promising activity in patients with radiation-induced sarcoma. Toxicity profile was favourable, allowing prolonged home staying and rare treatment discontinuations. A larger prospective study is warranted to confirm these encouraging results in elderly with STS.     

Increased use of regional radiotherapy is associated with improved outcome in a population-based cohort of women with breast cancer with 1-3 positive nodes

Purpose

To examine use of and outcomes from adjuvant locoregional radiotherapy (LRRT) after breast-conserving surgery (BCS) for women with breast cancer with 1-3 positive nodes (1-3 N+) before and after the 1997 publication of randomised trial evidence of a survival advantage from post-mastectomy LRRT.

Methods

Data were analysed for 2768 women diagnosed between 1989 and 2005 and referred to the British Columbia Cancer Agency with newly diagnosed pT1-3 breast cancer with 1-3 N+, treated with BCS and RT. LRRT use was analysed over time. Ten-year Kaplan-Meier locoregional control (LRC), breast cancer-specific survival (BCSS) and overall survival (OS) curves were compared using the log-rank test. Cox regression modeling of LRC and BCSS were performed.

Results

LRRT use in patients with 1-3 N+ increased from 23% before 1997 to 57% after 1997. LRRT was associated with significant improvements in LRC, but not in DRFS, BCSS, or OS. 10--year LRC was 89% with local RT alone and 93% with LRRT (p = 0.006). On multivariable analysis, LRRT was associated with improved LRC compared to local RT alone (HR 0.55, 95% CI: 0.40-0.77), but not with significant BCSS differences. Margin status, grade, % positive nodes, and hormonal therapy were significant predictors for LRC, while tumour size, grade, % positive nodes, and hormonal therapy significantly affected BCSS.

Conclusion

Post-BCS LRRT use in British Columbia increased almost threefold in patients with 1-3 N+ after 1997. Adjuvant LRRT was associated with improved LRC, but not with improved BCSS compared to breast RT alone.     

Retrospective analysis of definitive radiotherapy for patients with superficial esophageal carcinoma: Consideration of the optimal treatment method with a focus on late morbidity

Purpose

To evaluate the clinical efficacy of definitive radiotherapy for patients with superficial esophageal cancer.

Material and methods

From 1990 through 2006, 97 patients with stage I disease were treated with radiotherapy with or without chemotherapy. All patients were diagnosed with panesophagoscopy and computed tomography. Chemotherapy was added in 61 patients, and intra-cavitary brachytherapy (ICBT) was used in 27 patients.

Results

The patients were 90 men and seven women with a median age of 65.7 years (range; 41-89). At last follow-up with a median follow-up duration of 35.7 months, 3 year-overall and progression-free survival (PFS) rates were 81.5% (95% C.I. = 73.3-89.7%) and 55.8% (95% C.I. = 45.2-66.4%), respectively. Shorter tumor length was a significantly favorable factor for the PFS rate (P = 0.02) and local failure-free (LFF) rate (P = 0.007) on both univariate and multivariate analyses. Although the addition of ICBT had no apparent benefit for survival or tumor control, the rate of severe adverse effects including lethal esophageal ulcers, showed a higher tendency in patients receiving ICBT.

Conclusions

Our results regarding efficacy from the viewpoint of organ preservation are promising. Special care would be taken for the use of ICBT for patients with superficial esophageal cancer, especially if they have received chemoradiotherapy.     

Local control with conventional and hypofractionated adjuvant radiotherapy after breast-conserving surgery for ductal carcinoma in-situ

Purpose

Adjuvant whole breast radiotherapy (WBRT) for ductal carcinoma in situ (DCIS) improves local control, however an optimal dose fractionation remains undefined. WBRT following breast-conserving surgery for invasive breast cancer demonstrates equivalent efficacy and morbidity for conventional and hypofractionated treatment. Our group policy allowed for the use of both schedules, therefore we compared local control in women with DCIS following breast-conserving surgery.

Patients and methods

Two hundred and sixty-six patients treated between January 1999 and December 2004 with conventional (50 Gy in 25 fractions) or hypofractionated (42.4 Gy in 16 fractions or 40 Gy/16 + 12.5 Gy boost) WBRT after breast-conserving surgery for DCIS were retrospectively reviewed. Median follow-up was 3.76 years (range 0.1-8.9 years).

Results

One hundred and four patients (39%) were treated with conventional and 162 (61%) with hypofractionated WBRT. The median age was 56.7 years (range 32.2-83.8 years), and prognostic features were well matched in both groups, apart from a small increase in tumour size in the conventional arm (1.75 vs. 2.12 cm, p = 0.05). Actuarial risk of recurrence at 4 years was 7% with hypofractionated WBRT and 6% with the conventional schedule (p = 0.9). Univariate analysis showed an increased risk of recurrence with high nuclear grade tumours (11% at 4 years for grade 3 vs. 4% for grade 1/2, p = 0.029).

Conclusions

Hypofractionated adjuvant WBRT following breast-conserving surgery for DCIS has comparable local control to a conventional radiation schedule. Hypofractionated WBRT is more convenient for patients, has equivalent morbidity and should be considered in this patient group.     

A phase I study of nimotuzumab in combination with radiotherapy in stages IIB-IV non-small cell lung cancer unsuitable for radical therapy: Korean results

Purpose

This study was undertaken to determine safety and tolerability of nimotuzumab, a humanized anti-epidermal growth factor receptor monoclonal antibody, in combination with radiotherapy in stages IIB-IV non-small cell lung cancer (NSCLC) patients who are unsuitable for radical therapy or chemotherapy.

Methods

Nimotuzumab (100 mg, 200 mg and 400 mg) was administered weekly from week 1 to week 8 with palliative radiotherapy (30-36 Gy, 3 Gy/day). If tumor control was achieved, nimotuzumab was continued every 2 weeks until unacceptable toxicity or disease progression. Serial skin biopsies were collected for pharmacodynamic assessment.

Results

Fifteen patients were enrolled in the study, with cohorts of five patients assigned in each dose level of nimotuzumab. Patients and disease characteristics included median age 73 years; Eastern Cooperative Oncology Group performance status (PS) 0-1/2 (n = 3/12); female sex (n = 2); adenocarcinoma (n = 5); never-smoker status (n = 2); and stages IIB/IIIB/IV (n = 1/8/6). All patients were unable to tolerate radical therapy because of old age or multiple comorbidities. The most commonly reported adverse events were lymphopenia and asthenia (grades 1-2 in most patients). No skin rash or allergic toxicities appeared. Dose-limiting toxicity occurred with pneumonia with grade 4 neutropenia at the 200 mg dose of nimotuzumab. Objective response rate and disease control rate inside the radiation field were 46.7% and 100.0%, respectively.

Conclusions

Nimotuzumab in combination with radiotherapy is well-tolerated and feasible. Further clinical investigation of nimotuzumab in NSCLC patients is warranted.     

Diverging prognostic impacts of hypoxic markers according to NSCLC histology

Background

We aimed to explore the prognostic impact of the hypoxia induced factors (HIFαs) 1-2 and the metabolic HIF-regulated glucose transporter GLUT1, lactate dehydrogenase 5 (LDH5) and carbonic anhydrase IX (CAIX) in non-small cell lung cancer (NSCLC).

Methods

Tumor and stroma tissue samples from 335 unselected patients with stage I-IIIA NSCLC were obtained and tissue microarrays constructed. Immunohistochemistry was used to evaluate expression.

Results

For squamous cell carcinoma patients, high tumor cell expression of HIF1α and low stromal cell expression of HIF1α and HIF2α correlated significantly with a poor disease-specific survival (DSS) in both univariate (tumor HIF1α, P = 0.001; stromal HIF1α, P = 0.009; stromal HIF2α, P = 0.005) and multivariate analyses (tumor HIF1α, HR = 3.3, P = 0.001; stromal HIF1α, HR = 2.1, P = 0.008; stromal HIF2α, HR 2.3, P = 0.005). Among adenocarcinoma patients high tumor expression of GLUT1 and low stromal expression of LDH5 correlated significantly with a poor DSS in both univariate (GLUT1, P = 0.01; LDH5, P = 0.03) and multivariate analyses (GLUT1, HR = 1.9, P = 0.046; LDH5, HR = 2.3, P = 0.03).

Conclusion

These markers show highly diverging prognostic impacts between histological subgroups and between tumor and stromal compartments in NSCLC.     

Stereotactic body radiotherapy for local boost irradiation in unfavourable locally recurrent gynaecological cancer

Purpose

To evaluate outcome of radiotherapy for locally recurrent cervical and endometrial cancer.

Materials and methods

Nineteen patients were treated for a locally recurrent cervical (n = 12) or endometrial (n = 7) cancer median 26 months after initial surgery (n = 18) or radiotherapy (n = 1). The whole pelvis was irradiated with 50 Gy conventionally fractionated radiotherapy (n = 16). Because of large size of the recurrent cancer (median 4.5 cm) and peripheral location (n = 12), stereotactic body radiotherapy (SBRT; median 3 fractions of 5 Gy to 65%) was used for local dose escalation instead of (n = 16) or combined with (n = 3) vaginal brachytherapy.

Results

After median follow-up of 22 months, 3-year overall survival was 34% with systemic progression the leading cause of death (7/10). Median time to systemic progression was 16 months. Three local recurrences resulted in a local control rate of 81% at 3 years. No correlation between survival, systemic or local control and any patient or treatment characteristic was observed. The rate of late toxicity > grade II was 25% at 3 years: two patients developed a grade IV intestino-vaginal fistula and one patient suffered from a grade IV small bowel ileus.

Conclusion

Image-guided SBRT for local dose escalation resulted in high rates of local control but was associated with significant late toxicity.     

Association between plasma hepatocyte growth factor and gefitinib resistance in patients with advanced non-small cell lung cancer

Purpose

It has been suggested that hepatocyte growth factor (HGF) and insulin-like growth factor binding protein (IGFBP)-3 are associated with gefitinib resistance in non-small cell lung cancer (NSCLC). We investigated the predictive and prognostic roles of these proteins in NSCLC patients treated with gefitinib.

Patients and methods

Of 106 patients enrolled in a randomized phase II study of gefitinib, 97 had plasma samples available for ELISA testing. Of these samples, seven and eight, respectively, had HGF and IGFBP-3 values that could not be measured. Therefore, the correlations between clinical outcomes and plasma levels of HGF and IGFBP-3 were evaluated in 90 and 89 patients, respectively.

Results

Plasma HGF levels were significantly higher in older patients, male patients, patients with squamous cell carcinoma, current smokers, and patients with epidermal growth factor receptor (EGFR) wild-type tumors. Low HGF levels were significantly associated with higher response rate, and longer progression-free survival (PFS) and overall survival (OS) irrespective of EGFR mutation status. In a multivariate analysis, the presence of EGFR mutations (P = 0.002) and low HGF levels (P = 0.031) were independently predictive of longer PFS, and an ECOG PS of 0 (P = 0.001) and low HGF levels (P = 0.002) were independently predictive of longer OS. No statistically significant differences were found for IGFBP-3.

Conclusion

High HGF levels are significantly associated with resistance to gefitinib and can be used as a predictive marker for the differential outcome of gefitinib treatment in NSCLC irrespective of EGFR mutation status.     

High-dose radiotherapy or concurrent chemo-radiation in lung cancer patients only induces a temporary, reversible decline in QoL

Background and purpose

Aggressive radiotherapy or concurrent chemo-radiation therapy for lung cancer leads to a high incidence of severe, mostly esophageal, toxicity. The purpose of this study was to investigate the evolution of quality of life (QoL) in patients with lung cancer, selected for curative radiotherapy (RT) or chemo-RT.

Methods

Seventy-five lung cancer patients completed a longitudinal the EORTC QLQ-C30 and LC13. Linear mixed regression models were fitted to investigate the impact of different factors on overall QoL.

Results

Overall QoL decreased shortly after the end of RT (4 points, p = 0.19), but increased back to baseline within 3 months. Mean scores of role functioning (p = 0.018), cognitive functioning (p = 0.002), dyspnoea (EORTC QLQ-LC13; p = 0.043), dysphagia (p = 0.005) and hoarseness (p = 0.029), showed a significant worsening over time. Emotional functioning (p = 0.033) improved significantly over time.Severe esophagitis (?grade 2) was reported in only 12% of the patients. Next to maximal esophageal toxicity ?grade 2 (p = .0.010), also tumor stage IIIA (p < 0.001), tumor stage IIIB (p = 0.003), gender (p = 0.042) and fatigue (p < 0.001) appeared to be significant predictors of QoL.

Conclusion

High-dose radiotherapy or concurrent chemo-radiation in the treatment of lung cancer seems to be a well-tolerated treatment option with preservation of QoL.