Radiotherapy of choroidal metastases.

Abstract Purpose: This retrospective study was undertaken to clarify the role of high energy external beam radiation therapy (EBRT) and to determine its safety and efficacy on local control and visual acuity in patients suffering from choroidal metastases (CM). Materials and methods: The records of 58 consecutive patients treated with EBRT between 1970 and 1993 were analyzed. The female to male ratio was 2.9 and the median age was 59 years (range 40–81 years). Thirty-six patients (62%) had unilateral CM and 22 patients had bilateral CM. The mean number of lesions per eye was two. Retinal detachment was present in 65% of cases. The primary tumour (PT) was breast carcinoma for 38 patients (75%), lung carcinoma for 10 patients (17%) and gastrointestinal, genitourinary or unknown PT for the remaining 10 patients. The median interval of time between the PT and the CM was 55 months (range 0–228 months). All patients were treated with megavoltage irradiation. The median prescribed dose was 35.5 Gy (range 20–53 Gy) normalized at a 2 Gy per fraction schedule with an a/b value of 10 Gy. Various techniques were used and whenever possible the lens was spared. Ten patients with unilateral disease were treated in both eyes. Results: The tumour response was slow. When assessed after 3 months or more, the complete response rate was 53% with significantly better results for doses higher than 35.5 Gy (72 versus 33%; P = 0.009). Visual acuity was improved or stabilized in 62% of patients, with also significantly better results when doses higher than 35.5 Gy (P = 0.014) were administered. Amongst 26 patients with unilateral CM who had no elective contralateral irradiation, three developed metastasis in the opposite eye versus none of the 10 patients who had bilateral irradiation. Five complications occurred (three cataracts, one retinopathy and one glaucoma). Conclusion: Radiation therapy is an efficient and safe palliative treatment for choroidal metastases and it helps the preservation of vision. Thus, there is a major impact on the quality of life in a group of patients with an almost uniformly fatal prognosis. Both tumour response and visual acuity are significantly improved if doses higher than 35.5 Gy are administered. Whenever possible, a lens sparing technique should be used. Ó 1998 Elsevier Science Ireland Ltd

The Reasons for Discrepancies in TargetVolume Delineation: A SASRO Study on Head-and-Neck and Prostate Cancers

Purpose: : To understand the reasons for differences in the delineation of target volumes between physicians. Material and Methods: : 18 Swiss radiooncology centers were invited to delineate volumes for one prostate and one head-and-neck case. In addition, a questionnaire was sent to evaluate the differences in the volume definition (GTV [gross tumor volume], CTV [clinical target volume], PTV [planning target volume]), the various estimated margins, and the nodes at risk. Coherence between drawn and stated margins by centers was calculated. The questionnaire also included a nonspecific series of questions regarding planning methods in each institution. Results: : Fairly large differences in the drawn volumes were seen between the centers in both cases and also in the definition of volumes. Correlation between drawn and stated margins was fair in the prostate case and poor in the head-and-neck case. The questionnaire revealed important differences in the planning methods between centers. Conclusion: : These large differences could be explained by (1) a variable knowledge/interpretation of ICRU definitions, (2) variable interpretations of the potential microscopic extent, (3) difficulties in GTV identification, (4) differences in the concept, and (5) incoherence between theory (i.e., stated margins) and practice (i.e., drawn margins

Decrease in Hemoglobin Levels Following Surgery Influences the Outcome in Head and Neck Cancer Patients Treated with Accelerated Postoperative Radiotherapy

Aim: To assess the influence of hemoglobin (Hb) levels in locally advanced head and neck cancer (LAHNC) patients treated with surgery and postoperative radiotherapy (PORT). Material and Methods: Pre- and postoperative Hb levels were collected in 79 patients treated with surgery followed by accelerated PORT for LAHNC. Median follow-up was 52months (range 12-95months). Results and Discussion: Four-year overall survival (OS) rate was 51%. Neither pre- nor postoperative Hb level (<120 or 130g/l in women or men, respectively) influenced the outcome. However, when Hb decrease between pre- and postoperative Hb values was taken into account, 4-year OS was significantly higher in patients with Hb difference less than 38g/l (quartile value) compared with those with Hb decrease 38g/l or more (61% versus 16%, P=0.008). Conclusion: Decrease in Hb level by more than 38g/l after surgery secondary to blood loss influences the outcome when postoperative RT is indicate

Feasibility and Efficacy of Accelerated Weekly Concomitant Boost Postoperative Radiation Therapy Combined with Concomitant Chemotherapy in Patients with Locally Advanced Head and Neck Cancer

Background: The aim of this study was to assess feasibility and efficacy of weekly concomitant boost accelerated postoperative radiation therapy (PORT) with concomitant chemotherapy (CT) in patients with locally advanced head and neck cancer (LAHNC). Methods and Materials: Conformal or intensity-modulated 66-Gy RT was performed in 5.5weeks in 40 patients. Cisplatin was given at days 1, 22, and 43. Median follow-up was 36months. Results and Discussion: Grade 3 mucositis, dysphagia, and erythema was observed in ten (25%), nine (23%), and six (13%) patients, respectively. Grade 3 or more anemia was observed in two (6%) patients, and leukopenia in five (13%) patients. No grade 3 or 4 thrombocytopenia was observed. Grade 3 nephrotoxicity was observed in one patient (3%). No treatment-related mortality was observed. Grade 2 or more xerostomia and edema were observed in ten (25%) and one (3%) patient, respectively. Locoregional relapse occurred in eight patients, and seven patients developed distant metastases. Median time to locoregional relapse was 6months. Three-year overall, disease-free survival, and locoregional control rates were 63%, 62%, and 81%, respectively. Multivariate analysis revealed that the only prognostic factor was nodal status. Conclusion: Reducing overall treatment time using accelerated PORT/CT by weekly concomitant boost (six fractions per week) combined with concomitant cisplatin CT is easily feasible with acceptable morbidit

Primary breast lymphoma: patient profile, outcome and prognostic factors. A multicentre rare cancer network study

Background: To asses the clinical profile, treatment outcome and prognostic factors in primary breast lymphoma (PBL). Methods: Between 1970 and 2000, 84 consecutive patients with PBL were treated in 20 institutions of the Rare Cancer Network. Forty-six patients had Ann Arbor stage IE, 33 stage IIE, 1 stage IIIE, 2 stage IVE and 2 an unknown stage. Twenty-one underwent a mastectomy, 39 conservative surgery and 23 biopsy; 51 received radiotherapy (RT) with (n = 37) or without (n = 14) chemotherapy. Median RT dose was 40 Gy (range 12-55 Gy). Results: Ten (12%) patients progressed locally and 43 (55%) had a systemic relapse. Central nervous system (CNS) was the site of relapse in 12 (14%) cases. The 5-yr overall survival, lymphoma-specific survival, disease-free survival and local control rates were 53%, 59%, 41% and 87% respectively. In the univariate analyses, favorable prognostic factors were early stage, conservative surgery, RT administration and combined modality treatment. Multivariate analysis showed that early stage and the use of RT were favorable prognostic factors. Conclusion: The outcome of PBL is fair. Local control is excellent with RT or combined modality treatment but systemic relapses, including that in the CNS, occurs frequentl

Primary breast lymphoma: Patient profile, outcome and prognostic factors. A multicentre Rare Cancer Network study

BACKGROUND: To asses the clinical profile, treatment outcome and prognostic factors in primary breast lymphoma (PBL). METHODS: Between 1970 and 2000, 84 consecutive patients with PBL were treated in 20 institutions of the Rare Cancer Network. Forty-six patients had Ann Arbor stage IE, 33 stage IIE, 1 stage IIIE, 2 stage IVE and 2 an unknown stage. Twenty-one underwent a mastectomy, 39 conservative surgery and 23 biopsy; 51 received radiotherapy (RT) with (n = 37) or without (n = 14) chemotherapy. Median RT dose was 40 Gy (range 12-55 Gy). RESULTS: Ten (12%) patients progressed locally and 43 (55%) had a systemic relapse. Central nervous system (CNS) was the site of relapse in 12 (14%) cases. The 5-yr overall survival, lymphoma-specific survival, disease-free survival and local control rates were 53%, 59%, 41% and 87% respectively. In the univariate analyses, favorable prognostic factors were early stage, conservative surgery, RT administration and combined modality treatment. Multivariate analysis showed that early stage and the use of RT were favorable prognostic factors. CONCLUSION: The outcome of PBL is fair. Local control is excellent with RT or combined modality treatment but systemic relapses, including that in the CNS, occurs frequently

Radiotherapy Suppresses Angiogenesis in Mice through TGF-βRI/ALK5-Dependent Inhibition of Endothelial Cell Sprouting

BACKGROUND: Radiotherapy is widely used to treat cancer. While rapidly dividing cancer cells are naturally considered the main target of radiotherapy, emerging evidence indicates that radiotherapy also affects endothelial cell functions, and possibly also their angiogenic capacity. In spite of its clinical relevance, such putative anti-angiogenic effect of radiotherapy has not been thoroughly characterized. We have investigated the effect of ionizing radiation on angiogenesis using in vivo, ex vivo and in vitro experimental models in combination with genetic and pharmacological interventions. PRINCIPAL FINDINGS: Here we show that high doses ionizing radiation locally suppressed VEGF- and FGF-2-induced Matrigel plug angiogenesis in mice in vivo and prevented endothelial cell sprouting from mouse aortic rings following in vivo or ex vivo irradiation. Quiescent human endothelial cells exposed to ionizing radiation in vitro resisted apoptosis, demonstrated reduced sprouting, migration and proliferation capacities, showed enhanced adhesion to matrix proteins, and underwent premature senescence. Irradiation induced the expression of P53 and P21 proteins in endothelial cells, but p53 or p21 deficiency and P21 silencing did not prevent radiation-induced inhibition of sprouting or proliferation. Radiation induced Smad-2 phosphorylation in skin in vivo and in endothelial cells in vitro. Inhibition of the TGF-beta type I receptor ALK5 rescued deficient endothelial cell sprouting and migration but not proliferation in vitro and restored defective Matrigel plug angiogenesis in irradiated mice in vivo. ALK5 inhibition, however, did not rescue deficient proliferation. Notch signaling, known to hinder angiogenesis, was activated by radiation but its inhibition, alone or in combination with ALK5 inhibition, did not rescue suppressed proliferation. CONCLUSIONS: These results demonstrate that irradiation of quiescent endothelial cells suppresses subsequent angiogenesis and that ALK5 is a critical mediator of this suppression. These results extend our understanding of radiotherapy-induced endothelial dysfunctions, relevant to both therapeutic and unwanted effects of radiotherapy