Dose fractionation and tumour repopulation in radiotherapy for bladder cancer

Maciejewski, B.; Majewski, S.A.

doi:10.1016/0167-8140(91)90033-d

Cited by 153 publications

(51 citation statements)

References 26 publications

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“…Other studies that have used Ki-67 as a marker of proliferation in transitional cell bladder cancer have reported a significantly lower progression-free and disease-specific survival rates in patients with higher Ki-67 indices (Popov et al, 1997;Lara et al, 1998;Moonen et al, 1998a;Rodel et al, 2000). Clinical data relating the effect of treatment duration on bladder outcome are equivocal (Maciejewski and Majewski, 1991;De Neve et al, 1995;Moonen et al, 1998b).…”

Section: P=00021mentioning

confidence: 99%

GLUT1 and CAIX as intrinsic markers of hypoxia in bladder cancer: relationship with vascularity and proliferation as predictors of outcome of ARCON

et al. 2003

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Glucose transporter-1 protein (GLUT1) and carbonic anhydrase IX (CAIX) are regulated by hypoxia inducible factor-1 (HIF-1) and have been studied as putative intrinsic cellular markers for hypoxia. This study directly compares CAIX and GLUT1 with pimonidazole binding in a prospective series of bladder cancer patients and also studies the prognostic significance of the markers, in combination with vascularity and proliferation, in a retrospective series of bladder cancer patients treated in a phase II trial of radical radiotherapy with carbogen and nicotinamide (ARCON). A total of 21 patients with a diagnosis of transitional cell carcinoma of the bladder received 0.5 g m À2 pimonidazole. Serial tumour sections were stained for pimonidazole, GLUT1 and CAIX and compared. Tissue sections obtained from a series of 64 patients previously treated for invasive bladder cancer using ARCON were stained for GLUT1 and CAIX together with Ki-67 and CD31/34. There was a good geographical colocalisation of both intrinsic markers with pimonidazole and a highly significant agreement in individual patients; correlation coefficients were 0.82 (P ¼ 0.0001) for GLUT1 and 0.74 (Po0.0001) for CAIX. In both series of patients, the intrinsic hypoxia markers were highly correlated with each other and a correlation with proliferation was also evident in the retrospective study. In univariate and multivariate analyses, GLUT1 and CAIX were independent predictors for overall and cause specific survival. The hypoxia markers did not predict for local control or metastases-free survival although higher Ki-67 indices showed a trend towards local failure. The data suggest that both hypoxia modification and accelerated treatment may be valid treatment options in bladder cancer.

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Section: P=00021mentioning

confidence: 99%

GLUT1 and CAIX as intrinsic markers of hypoxia in bladder cancer: relationship with vascularity and proliferation as predictors of outcome of ARCON

et al. 2003

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“…A reduction in normal tissue morbidity may be possible with the use of hyperfractionation radiotherapy alone or combined with treatment acceleration. However, data on the importance of overall time in bladder carcinoma are contradictory, 26,27 and excess bowel morbidity was found when acceleration was coupled with conventional 2-Gy fractions. 28 Technical developments of conformal radiotherapy techniques and intensity-modulated radiotherapy, likewise, may enable a reduction in biologic dose delivered to normal tissues inevitably encompassed in the treatment fields.…”

Section: Discussionmentioning

confidence: 99%

Acute and late morbidity in the treatment of advanced bladder carcinoma with accelerated radiotherapy, carbogen, and nicotinamide

Hoskin

Rojas

Phillips

et al. 2005

Cancer

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BACKGROUND Accelerated radiotherapy combined with carbogen and nicotinamide (ARCON) to overcome tumor hypoxia and cell proliferation achieved high tumor control and survival in Phase II studies of patients with advanced head and neck and bladder carcinomas. Thus, morbidity and treatment outcomes from the latter study were analyzed to evaluate the therapeutic potential of ARCON. METHODS Acute and late morbidity was assessed in 105 patients with high‐grade superficial or muscle‐invasive bladder carcinoma who were given accelerated radiotherapy (50–55 grays in 4 weeks) with carbogen alone or with ARCON. Urinary dysfunction was scored based on daytime frequency, nocturia, incontinence, dysuria, hematuria, and urgency. Bowel morbidity was based on stool frequency and consistency, rectal discharge, blood loss, and medication. Endpoints for treatment outcome were overall survival, disease‐free survival, and locoregional control. RESULTS Nearly all patients experienced reduced ability to retain urine beyond 2 hours, although 20–30% had almost normal function at night. Incidence of acute moderate or worse dysuria was 41% with ARCON and 56% with carbogen; 96% and 76% of patients, respectively, had bowel frequencies ≥ 3 times per day. By 10–12 weeks from the start of radiotherapy, acute reactions returned to baseline levels. At 3 years, the daytime frequency ≤ 2 times per hour was ≈ 75% in both arms. Incidence of severe hematuria (≤ 25%) and urinary urgency (≤ 16%) was much lower. No more than 6% of patients had severe bowel morbidity. With most assays, the differences between schedules were not significant either for acute or late morbidity. Local tumor control and survival rates at 3 years were 53% and 43%, respectively, for ARCON, similar to the rates for carbogen alone. CONCLUSIONS Historical comparisons suggested no overt increase in normal tissue radiosensitivity when adding carbogen and nicotinamide. Although, for some endpoints, the incidence of late sequelae was higher than expected, overall morbidity was no worse than reported by others. The data indicated that ARCON could achieve a therapeutic gain in patients with advanced bladder carcinoma. A Phase III, randomized, multicenter trial is underway currently in the United Kingdom to evaluate these findings. Cancer 2005. © 2005 American Cancer Society.

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“…Die meisten Autoren berichten über eine Abnahme der Kontroll-und Überlebensrate, wenn die Behandlungszeit verlängert wurde [8,17,29]. Unsere Studienergebnisse zeigen, daß verlängerte Behandlungszeiten wegen geplanter Therapieunterbrechungen mit einem kürzeren Überleben korrelieren.…”

Section: Diskussionunclassified