Jos de Jong

The prognostic impact of quality of life assessed with the EORTC QLQ-C30 in inoperable non-small cell lung carcinoma treated with radiotherapy

PURPOSE The purpose of this study was to assess the prognostic significance of pretreatment quality of life (QoL) scores and symptom scores in a group of patients treated with high dose radiotherapy. MATERIAL AND METHODS A total of 198 patients treated with external irradiation (>/=60 Gy) were included. In all these patients, baseline QoL was assessed using the EORTC QLQ-C30. The prognostic significance of a number of non-QoL and QoL parameters with regard to survival was estimated in both univariate and multivariate analyses. RESULTS In a multivariate model including the non-QoL parameters, performance status, weight loss and N-classification were independent prognostic factors for survival. After entering the QoL parameters in the model, global QoL was the strongest prognostic factor, while performance status lost its significance. Subsequently, a significant interaction term was found between N-classification and global QoL, indicating that global QoL was an independent prognostic factor but that the effect varied as a function of N-status. In N+ patients, the median survival in the group with low scores for global QoL was 4.5 months, which was significantly worse (P<0.0001) compared with the high score group in which the median survival was 12.9 months. CONCLUSION Global QoL is a strong prognostic factor for survival in patients with NSCLC who have pathological lymph nodes at presentation and who are treated with radical or curative radiotherapy.

CD44 Expression Predicts Local Recurrence after Radiotherapy in Larynx Cancer

Purpose: To find molecular markers from expression profiling data to predict recurrence of laryngeal cancer after radiotherapy. Experimental Design: We generated gene expression data on pre-treatment biopsies from 52 larynx cancer patients. Patients developing a local recurrence were matched for T-stage, subsite, treatment, gender and age with non-recurrence patients. Candidate genes were then tested by immunohistochemistry on tumor material from a second series of 76 patients. Both series comprised early stage cancer treated with radiotherapy alone. Finally, gene expression data of eight larynx cancer cell lines with known radiosensitivity were analyzed. Results: Nineteen patients with a local recurrence were matched with 33 controls. Gene sets for hypoxia, proliferation and intrinsic radiosensitivity did not correlate with recurrence, whereas expression of the putative stem cell marker CD44 did. In a supervised analysis, probes for all three splice variants of CD44 on the array appeared in the top 10 most significantly correlated with local recurrence. Immunohistochemical analysis of CD44 expression on the independent validation series confirmed CD44s predictive potential. In 8 larynx cancer cell lines, CD44 gene expression did not correlate with intrinsic radiosensitivity although it did correlate significantly with plating efficiency, consistent with a relationship with stem cell content. Conclusions: CD44 was the only biological factor tested which significantly correlated with response to radiotherapy in early stage larynx cancer patients, both at the mRNA and protein levels. Further studies are needed to confirm this and to assess how general these findings are for other head and neck tumor stages and sites. Clin Cancer Res; 16(21); 5329–38. ©2010 AACR.

External irradiation versus external irradiation plus endobronchial brachytherapy in inoperable non-small cell lung cancer: a prospective randomized study.

Abstract Purpose : No randomized studies are available on the additional value of endobronchial brachytherapy (EBB) to external irradiation (XRT) regarding palliation of respiratory symptoms (RS). A prospective randomized study was initiated to test the hypothesis that the addition of EBB to XRT provides higher levels of palliation of dyspnea and other RS and improvement of quality of life (QoL) in patients with non-small cell lung cancer (NSCLC) with endobronchial tumour. Materials and methods : Patients with previously untreated NSCLC, stages I-IIIb, WHO-performance status of 0–3 and with biopsy proven endobronchial tumour in the proximal airways were eligible. EBB consisted of two fractions of 7.5 Gy at 1 cm on day 1 and 8. XRT started at day 2. The XRT dose was 30 Gy (2 weeks) or 60 Gy (6 weeks). The EORTC QLQ-C30 and QLQ-LC13 were assessed before treatment and 2 weeks, 6 weeks, 3, 6 and 12 months after treatment. Re-expansion of collapsed lung was tested by the inspiratory vital capacity (IVC) and CT scan of the chest. Results : Ninety-five patients were randomized between arm 1 (XRT alone) ( n =48) or arm 2 (XRT+EBB) ( n =47). The arms were well balanced regarding pre-treatment characteristics and QoL scores. The compliance for QoL-assessment was >90% at all times. No significant difference between the trial arms was observed with respect to response of dyspnea. However, a beneficial effect of EBB was noted concerning the mean scores of dyspnea over time ( P =0.02), which lasted for 3 months. This benefit was only observed among patients with an obstructing tumour of the main bronchus. A higher rate of re-expansion of collapsed lung was observed in arm 2 (57%) compared to arm 1 (35%) ( P =0.01). The inspiratory vital capacity (IVC) assessed 2 weeks after radiotherapy improved with 493 cm 3 in arm 2 and decreased 50 cm 3 in arm 1 ( P =0.03). No difference was noted regarding the incidence of massive haemoptysis (13 vs. 15%). Conclusion : The addition of EBB to XRT in NSCLC is safe and provides higher rates of re-expansion of collapsed lung resulting in a transient lower levels of dyspnea. This beneficial effect was only observed among patients with obstructing tumours in the main bronchus.

Human papillomavirus reduces the prognostic value of nodal involvement in tonsillar squamous cell carcinomas.

Assessment of the prognostic value of nodal status in relation to human papillomavirus (HPV) status and the various treatment modalities in tonsillar squamous cell carcinomas (TSCC).

Multidimensional assessment of voice characteristics after radiotherapy for early glottic cancer

Objectives/Hypothesis: To assess voice characteristics of patients following radiotherapy for early glottic cancer through a multidimensional analysis protocol including vocal function and voice quality measures. Methods: Voice analyses were performed for 60 patients treated with radiotherapy (66 Gy/33 fractions, 60 Gy/30 fractions, or 60 Gy/25 fractions) for early T1 glottic cancer and 20 matched control speakers. There was a longitudinal group of 10 patients for whom data were collected before as well as 6 months and 2 years after radiation. Furthermore, data were collected for five separate groups of 10 patients each, before, 6 months after, 2 years after, 3 to 7 years after, and 7 to 10 years after radiation. Vocal function was investigated by means of videolaryngostroboscopy, phonetography, maximum phonation time, and phonation quotient measures. Voice quality was assessed by means of objective acoustical analysis and subjective perceptual ratings by trained raters. Results: Voice characteristics of patients were decreased before radiotherapy, improved after treatment, and became comparable to the voice characteristics of control speakers in at least 55% of the patients. Following radiotherapy, deviant voice quality was mainly negatively affected by increased age and stripping the vocal cord for initial diagnosis. Stroboscopy revealed that next to increasing age and stripping the vocal cord, continued smoking after treatment decreased vocal function following radio‐therapy. Conclusion: Voices of patients diagnosed with early glottic cancer improved but did not normalize fully after radiotherapy. Stripping the vocal cord for initial diagnosis and continued smoking after treatment decreased voice characteristics. A multidimensional analysis protocol including perceptual and acoustical analysis of voice quality and stroboscopic analysis of vocal function is recommended to investigate voice characteristics following treatment for early glottic cancer.

CONSEQUENCES OF VOICE IMPAIRMENT IN DAILY LIFE FOR PATIENTS FOLLOWING RADIOTHERAPY FOR EARLY GLOTTIC CANCER: VOICE QUALITY, VOCAL FUNCTION, AND VOCAL PERFORMANCE

PURPOSE To assess consequences of voice impairment in daily life for patients following radiotherapy for early glottic cancer, by means of a multidimensional analysis protocol including voice quality, vocal function, and vocal performance measures. METHODS AND MATERIALS A total of 60 men treated with radiotherapy (66 Gy/33 fractions, 60 Gy/30 fractions, 60 Gy/25 fractions) for early T1 glottic cancer and 20 matched control speakers filled in questionnaires on vocal performance. Furthermore, perceptual analyses of voice quality and stroboscopic measures of vocal function were performed. There was a longitudinal group of 10 patients from whom data were collected before, as well as 6 months and 2 years after, radiation. Furthermore, data were collected on 5 separate groups of 10 patients each: before, 6 months after, 2 years after, 3-7 years after, and 7-10 years after radiation. RESULTS High correlations were found between self-ratings of vocal performance and several voice measures. Patients before radiotherapy experienced poor voice characteristics that improved 6 months to 10 years after treatment, and became comparable to vocal performance of control speakers in 50% of the patients. Following radiotherapy, deviant voice characteristics and consequences in daily life occurred significantly more often for patients in whom initial diagnosis consisted of stripping the vocal cord instead of biopsies and for patients who continued smoking after treatment. CONCLUSION Voice characteristics of patients diagnosed with early glottic cancer improved after radiotherapy, and became normal in half of our patients. Stripping the vocal cord for initial diagnosis and continued smoking after treatment decreased deviant voice characteristics.

A single session of intraluminal brachytherapy in palliation of oesophageal cancer

Between September 1987 and September 1993, 88 patients with oesophageal cancer were treated by a single session of intraluminal brachytherapy of 15 Gy prescribed at 1 cm distance from the central axis, using MDR137Cs (n = 51) during the first part of the study and HDR192Ir (n = 37) during the second part of the study. All patients were regarded as inoperable. Improvement of dysphagia, assessed 4-6 weeks after treatment, was noted in 50 of 75 (67%) evaluable patients, whereas swallowing ability was completely restored in 47% of them. Relapse of dysphagia occurred in 28 (37%) patients during follow-up. Additional palliative treatment consisted of endoprosthesis in 14 (19%), a second course of brachytherapy in 13 (17%), one or more dilatations only in 11 (15%) and laser treatment in four (5%) patients. One non-fatal haemorrhage and five fistulae occurred, all in the presence of tumour. Two severe ulcerations without evidence of tumour were noted, both managed by combined curative treatment. The median survival of the group investigated was 5.5 months. An exophytic, non-circular growth pattern was associated with a better response. In a multivariate analysis the presence of distant metastases (p = 0.0028), weight loss (p = 0.0051) and an exophytic growth pattern (p = 0.0199) were associated with a worse survival. The present data indicate that a single session of ILB is appropriate in the palliation of dysphagia in patients with inoperable oesophagal cancer showing bad prognostic signs. Up to now there has been no clear evidence for benefit of addition of ERT.

MASSIVE HAEMOPTYSIS AFTER RADIOTHERAPY IN INOPERABLE NON-SMALL CELL LUNG CARCINOMA : IS ENDOBRONCHIAL BRACHYTHERAPY REALLY A RISK FACTOR?

BACKGROUND AND PURPOSE This retrospective study was conducted to investigate whether endobronchial brachytherapy (EBB) is a risk factor for massive haemoptysis in patients primarily treated by a combination of EBB and external irradiation (XRT) for NSCLC. MATERIALS AND METHODS The records of 938 patients with inoperable NSCLC who were treated with XRT and/or EBB were reviewed. The patients were divided into five groups as follows: group XRT, treated by XRT alone (n = 421); group XRTelig, treated by XRT but eligible for EBB (n = 419); group XRTEBB, primarily treated with EBB+XRT (n = 62); group EBBrec, treated by EBB for recurrence after XRT (n = 23); and group EBB, treated by EBB alone (n = 13). EBB was delivered using HDR. Patients with bronchoscopy-proven endobronchial tumour in the proximal airways, i.e. the trachea, the main bronchus or lobar bronchus were considered eligible for EBB. RESULTS One hundred one out of 938 patients (10.8%) died from massive haemoptysis. The incidence was 4.3% in group XRT, 13.1% in group XRTelig and 25.4% in group XRTEBB. The differences between groups XRT and XRTelig as well as between groups XRTelig and XRTEBB were statistically significant (P<0.01). The incidence of massive haemoptysis depended significantly on the fraction size of brachytherapy. When two fractions of 7.5 Gy or a single fraction of 10 Gy were used, 11.1% of the patients died from massive haemoptysis. However, when a single dose of 15 Gy was used, 47.8% died from massive haemoptysis. In the multivariate analysis, a single dose of 15 Gy EBB was the most important prognostic factor for massive haemoptysis. CONCLUSION XRT+EBB as primary treatment for NSCLC does not lead to a higher risk of massive haemoptysis as compared to XRT alone when fraction sizes for EBB of 7.5 or 10 Gy are used. However, the risk of massive haemoptysis increases dramatically when a fraction size of 15 Gy is used.

Single-dose radiotherapy (6 Gy): palliation in painful bone metastases

Approximately 50% of patients with cancer develop bone metastases and these have an important influence on the quality of life. PURPOSE OF THE STUDY. To evaluate a lower dose than the one already proven to be effective (8 Gy) in the palliation of painful bone metastases. METHODS AND MATERIALS. In a prospective study we analyzed the pain relief, after a single dose of 6 Gy, in 170 patients with painful bone metastases. This was assessed by a questionnaire. RESULTS. A degree of pain relief, was achieved in 88% of the treatments and there was complete relief in 39%. When the treatment was given to the vertebrae, infield spinal cord compression developed in 9%, and when given to the pelvis or femur, infield fractures developed in 8%. CONCLUSION. We concluded that a single dose of 6 Gy was very effective in the palliation of painful bone metastases.

Loco-regional recurrences after mastectomy in breast cancer: prognostic factors and implications for postoperative irradiation

PURPOSE Potential risk factors including DNA flow cytometric-derived parameters predicting loco-regional recurrence (LRR) in early breast cancer were investigated. MATERIALS AND METHODS This study included 608 patients treated by modified radical mastectomy between 1982 and 1987. Recommendations regarding local treatment as well as adjuvant systemic therapy did not change during this period. Patients treated by adjuvant chemotherapy were randomized to receive additional medroxyprogesterone acetate (MPA) treatment. Only 59 (10%) patients received postoperative irradiation (XRT) to the chest wall and/or axillary lymph nodes; another 121 (20%) patients received XRT to the internal mammary nodes because of centromedially located tumours. RESULTS Patients were followed for a median period of 7.5 years. The event-free survival at 10 years was 50%. The cumulative incidence rate of LRR at 10 years was 18% (n = 93), either with (n = 30) or without (n = 63) concurrent distant metastases. The chest wall, regional lymph nodes or both were involved in 41 (44%), 38 (41%) and 12 (13%) patients, respectively. Multivariate analysis according to the Cox model revealed two factors associated with LRR, i.e. pT (P < 0.05) and nodal status (P < 0.05). In node-positive patients extracapsular tumour extension (ECE) and pT were independent risk factors. DNA ploidy and S-phase fraction did not yield additional information. Based on pT, nodal status and extracapsular extension of tumour growth a high risk (> 10%) and low risk (< 10%) group for LRR could be identified. CONCLUSIONS Results indicate that T-stage and nodal status, combined with ECE, may help to identify patients at risk for loco-regional recurrence, whereas DNA flow cytometry does not.