Long-Term Experience of Chemoradiotherapy Combined with Deep Regional Hyperthermia for Organ Preservation in High-Risk Bladder Cancer (Ta, Tis, T1, T2).

BACKGROUND: The aim of this study was to evaluate the efficacy and safety of chemoradiotherapy (RCT) combined with regional deep hyperthermia (RHT) of high-risk bladder cancer after transurethral resection of bladder tumor (TUR-BT). MATERIALS AND METHODS: Between 1982 and 2016, 369 patients with pTa, pTis, pT1, and pT2 cN0-1 cM0 bladder cancer were treated with a multimodal treatment after TUR-BT. All patients received radiotherapy (RT) of the bladder and regional lymph nodes. RCT was administered to 215 patients, RCT + RHT was administered to 79 patients, and RT was used in 75 patients. Treatment response was evaluated 4-6 weeks after treatment with TUR-BT. RESULTS: Complete response (CR) overall was 83% (290/351), and in treatment groups was RT 68% (45/66), RCT 86% (178/208), and RCT + RHT 87% (67/77). CR was significantly improved by concurrent RCT compared with RT (odds ratio [OR], 2.32; 95% confidence interval [CI], 1.05-5.12; p = .037), less influenced by hyperthermia (OR, 2.56; 95% CI, 0.88-8.00; p = .092). Overall survival (OS) after RCT was superior to RT (hazard ratio [HR], 0.7; 95% CI, 0.50-0.99; p = .045). Five-year OS from unadjusted Kaplan-Meier estimates was RCT 64% versus RT 45%. Additional RHT increased 5-year OS to 87% (HR, 0.32; 95% CI, 0.18-0.58; p = .0001). RCT + RHT compared with RCT showed a significantly better bladder-preservation rate (HR, 0.13; 95% CI, 0.03-0.56; p = .006). Median follow-up was 71 months. The median number of RHT sessions was five. CONCLUSION: The multimodal treatment consisted of a maximal TUR-BT followed by RT; concomitant platinum-based chemotherapy combined with RHT in patients with high-grade bladder cancer improves local control, bladder-preservation rate, and OS. It offers a promising alternative to surgical therapies like radical cystectomy. IMPLICATIONS FOR PRACTICE: Radical cystectomy with appropriate lymph node dissection has long represented the standard of care for muscle-invasive bladder cancer in medically fit patients, despite many centers reporting excellent long-term results for bladder preserving strategies. This retrospective analysis compares different therapeutic modalities in bladder-preservation therapy. The results of this study show that multimodal treatment consisting of maximal transurethral resection of bladder tumor followed by radiotherapy, concomitant platinum-based chemotherapy combined with regional deep hyperthermia in patients with Ta, Tis, T1-2 bladder carcinomas improves local control, bladder-preservation rate, and survival. More importantly, these findings offer a promising alternative to surgical therapies like radical cystectomy. The authors hope that, in the future, closer collaboration between urologists and radiotherapists will further improve treatments and therapies for the benefit of patients.

How Octogenarians with Bladder Cancer Are Treated in a Maximum-Care Hospital: The Real-Life Experience.

INTRODUCTION: With increasing life expectancy, curative treatment of octogenarians with urothelial carcinoma of the bladder (UCB) becomes more important. MATERIALS AND METHODS: The treatment modalities of 276 octogenarians with UCB who were treated at the University Hospital of Erlangen between 1982 and 2011 were assessed retrospectively. RESULTS: One hundred forty-six patients had non-muscle invasive bladder cancer (NMIBC) while 71 had muscle invasive bladder cancer (MIBC). No data was available for 59 patients. Eighty-five (58.2%) of the 146 patients with NMIBC received transurethral resection of the bladder tumor (TURBT) only, another 38 patients (26%) underwent additional intravesical therapy; and 8.9% were treated with radiochemotherapy (RCT), 4.1% with radiotherapy (RT), 1.4% with systemic chemotherapy and 1.4% with radical cystectomy (RC). Of the 71 patients suffering from MIBC, 39 (54.9%) received TURBT alone. A potentially curative therapy was performed on 31 of the 71 patients with MIBC (43.7%). Of these, 16 patients (51.6%) received RCT, 9 patients (29.0%) RT and 6 patients (19.4%) RC. In Kaplan-Meier analysis, patients with MIBC had better median overall survival with curative treatment compared to TURBT alone (28 vs. 9 months; p < 0.001, log-rank test). CONCLUSIONS: By offering a wide range of treatment options, over 43% of octogenarians with MIBC received a curative therapy at a maximum care hospital.

Lipiodol injections for optimization of target volume delineation in a patient with a second tumor of the oropharynx: A case report.

BACKGROUND: Lipiodol injections were administered in the head and neck area to improve gross tumor volume (GTV) definition for small-volume re-irradiation of a 63-year-old previously irradiated patient with a second tumor of the oropharynx in the posterior wall with longitudinal ligament infiltration (cT4cN0cM0). METHODS: The patient had dialysis-depending renal failure. On diagnostic computed tomography (CT), which was performed with intravenous contrast agent, the tumor in the oropharynx was not detectable. Because of dialysis-depending renal failure comorbidity, no contrast agent was applied in the planning CT and in the diagnostic magnetic resonance imaging (MRI) study. In each cross-sectional imaging study performed, the GTV, especially in craniocaudal extensions, was not safely delineable. Therefore, craniocaudal tumor margins were pharyngoscopically marked with Lipiodol injections, an iodine-containing contrast agent. RESULTS: In a second planning CT, the GTV could be defined with the help of the Lipiodol marks and small-volume re-irradiation was performed. No Lipiodol-associated side effects occurred in the patient. CONCLUSION: In the present case, the use of Lipiodol injections at the tumor margins facilitated the definition of the GTV.

Increased skin and mucosal toxicity in the combination of vemurafenib with radiation therapy.

BACKGROUND: Palliative radiotherapy is often required for patients with metastatic malignant melanoma in the case of bone or brain metastases. Since BRAF inhibitor therapy is highly efficient in V600-mutated melanomas, there is hesitation to stop it during radiotherapy. Consequently, radiotherapy under simultaneous vemurafenib treatment is frequently needed. CASE REPORT: We report the case of a patient receiving palliative radiotherapy of spinal bone metastases before and during vemurafenib therapy. The skin reactions were quantitatively scored using computer-assisted digital image evaluation. RESULTS: Radiotherapy without vemurafenib was tolerated very well, whereas radiotherapy under simultaneous vemurafenib treatment resulted in accentuated skin reactions. Furthermore, the patient developed dysphagia and had to be hospitalized for parenteral nutrition. In the quantitative analysis, there was a twofold increase in pigmentation and erythema of the irradiated skin area of the thoracic spine when vemurafenib was combined with radiotherapy compared with radiotherapy treatment alone. This is the first reported case of a patient showing no complications during radiotherapy without vemurafenib but remarkable skin and mucosal toxicity under concurrent vemurafenib therapy. Thus, a genetically conditioned individually elevated radiosensitivity can definitely be excluded. Compared with other reported cases, radiosensitization was not limited to the skin, but also affected the esophageal mucosa. CONCLUSION: Vemurafenib is a strong radiosensitizer. Patients receiving radiotherapy under simultaneous vemurafenib treatment should be monitored very closely.

Regional deep hyperthermia: impact of observer variability in CT-based manual tissue segmentation on simulated temperature distribution.

The aim of this study was to systematically investigate the influence of the inter- and intra-observer segmentation variation of tumors and organs at risk on the simulated temperature coverage of the target. CT scans of six patients with tumors in the pelvic region acquired for radiotherapy treatment planning were used for hyperthermia treatment planning. To study the effect of inter-observer variation, three observers manually segmented in the CT images of each patient the following structures: fat, muscle, bone and the bladder. The gross tumor volumes (GTV) were contoured by three radiation oncology residents and used as the hyperthermia target volumes. For intra-observer variation, one of the observers of each group contoured the structures of each patient three times with a time span of one week between the segmentations. Moreover, the impact of segmentation variations in organs at risk (OARs) between the three inter-observers was investigated on simulated temperature distributions using only one GTV. The spatial overlap between individual segmentations was assessed by the Dice similarity coefficient (DSC) and the mean surface distance (MSD). Additionally, the temperatures T90/T10 delivered to 90%/10% of the GTV, respectively, were assessed for each observer combination. The results of the segmentation similarity evaluation showed that the DSC of the inter-observer variation of fat, muscle, the bladder, bone and the target was 0.68 ± 0.12, 0.88 ± 0.05, 0.73 ± 0.14, 0.91 ± 0.04 and 0.64 ± 0.11, respectively. Similar results were found for the intra-observer variation. The MSD results were similar to the DSCs for both observer variations. A statistically significant difference (p < 0.05) was found for T90 and T10 in the predicted target temperature due to the observer variability. The conclusion is that intra- and inter-observer variations have a significant impact on the temperature coverage of the target. Furthermore, OARs, such as bone and the bladder, may essentially influence the homogeneity of the simulated target temperature distribution.