Hypopharyngeal and upper esophageal ulceration after cervical spine radiotherapy concurrent with crizotinib.

Herein, the authors describe the case of a 31-year-old female patient with primary metastatic adenocarcinoma of the lung referred for radiation therapy of newly diagnosed intramedullary spinal cord metastasis at C4/5 and an adjacent osteolytic lesion. Radiotherapy of the cervical spine level C3 to C5, including the whole vertebra, was performed with 30 Gy in 10 fractions. The patient's systemic therapy with crizotinib 250 mg twice daily was continued. After 8 fractions of radiation the patient developed increasing dysphagia. Ulceration of the hypopharynx and the upper esophagus were obvious in esophagoscopy and CT. Hospitalization for analgesia and percutaneous endoscopic gastrostomy (PEG) was required. First oral intake was possible 3 weeks after the onset of symptoms. The early onset, severity, and duration of mucositis seemed highly unusual in this case. A review of the literature failed to identify any reference to increased mucositis after radiation therapy concurrent with crizotinib, although references to such an effect with other tyrosine kinase inhibitors (TKI) were found. Nevertheless, the authors presume that a considerable risk of unexpected interactions exists. When crizotinib and radiotherapy are combined, heightened attention toward intensified reactions seems to be warranted.

Palliative radiotherapy--new approaches.

Most cancer patients will require radiation therapy some time during their disease. Thirty percent to 50% of all radiation treatments are palliative, either to alleviate symptoms or prophylactic to prevent deterioration of quality of life from local progressive disease. Radiotherapy is a locally effective tool. It typically causes no systemic and mostly mild acute side effects. We will provide an overview of principles, decision-making, and new developments in palliative radiation therapy.

Radiotherapeutic Options for Symptom Control in Breast Cancer.

SUMMARY: The majority of breast cancer patients will require radiation therapy at some time during the course of their disease. An estimated 30-50% of all radiation treatments are of palliative nature, either to alleviate symptoms or prophylactic to prevent deterioration of quality of life due to locally progressive disease. Radiotherapy is a locally effective tool, and typically causes no systemic and mostly mild acute side effects. The following article provides an overview of options and decision-making in palliative radiotherapy for symptom control.

The delineation of target volumes for radiotherapy of lung cancer patients.

PURPOSE: Differences in the delineation of the gross target volume (GTV) and planning target volume (PTV) in patients with non-small-cell lung cancer are considerable. The focus of this work is on the analysis of observer-related reasons while controlling for other variables. METHODS: In three consecutive patients, eighteen physicians from fourteen different departments delineated the GTV and PTV in CT-slices using a detailed instruction for target delineation. Differences in the volumes, the delineated anatomic lymph node compartments and differences in every delineated pixel of the contoured volumes in the CT-slices (pixel-by-pixel-analysis) were evaluated for different groups: ten radiation oncologists from ten departments (ROs), four haematologic oncologists and chest physicians from four departments (HOs) and five radiation oncologists from one department (RO1D). RESULTS: Agreement (overlap > or = 70% of the contoured pixels) for the GTV and PTV delineation was found in 16.3% and 23.7% (ROs), 30.4% and 38.6% (HOs) and 32.8% and 35.9% (RO1D), respectively. CONCLUSION: A large interobserver variability in the PTV and much more in the GTV delineation were observed in spite of a detailed instruction for delineation. The variability was smallest for group ROID where due to repeated discussions and uniform teaching a better agreement was achieved.

Prospective evaluation of quality of life after permanent prostate brachytherapy with I-125: importance of baseline symptoms and of prostate-V150.

BACKGROUND AND PURPOSE: Detailed knowledge of quality of life (QoL) after permanent I-125 brachytherapy may aid in counselling patients with early-stage prostate cancer. MATERIALS AND METHODS: Seventy-four consecutive patients with low-risk prostate cancer were asked to complete the EORTC QLQ-C30 questionnaire with the prostate-specific PR25 module before implant, four weeks and one year after implant (response rates 97%, 88% and 89%, respectively). Implant characteristics were correlated with QoL scores. RESULTS: Global QoL was stable from pre-treatment to one year after implant and similar to age-adjusted scores of healthy controls. Significant changes versus baseline in QLQ-C30 domains were worsened social function at four weeks, increased constipation at four weeks and at one year and improved emotional function at one year. PR25 urinary symptoms were significantly increased at four weeks and, despite some improvement, at one year; bowel symptoms were slightly increased. Both types of symptoms were most strongly related with pre-treatment symptom scores. Prostate-V150 was the only implant parameter significantly associated with both urinary and bowel symptoms at four weeks and one year. CONCLUSIONS: Limiting the high-dose subvolume in the prostate may be beneficial to reduce urinary and bowel symptoms but the major determinant of symptoms after I-125 implant is the baseline symptom level.

Pulmonary injury and tumor response after stereotactic body radiotherapy (SBRT): results of a serial follow-up CT study.

PURPOSE: To evaluate the CT morphological pattern of tumor response and pulmonary injury after stereotactic body radiotherapy (SBRT) for early stage non-small lung cancer (NSCLC) and pulmonary metastases. MATERIALS AND METHODS: Seventy patients (lesions n=86) with pulmonary metastases (n=48) or primary early stage NSCLC (n=38) were analyzed. Patients were treated with hypofractionated SBRT (three to eight fractions with a single dose between 6 and 12.5 Gy; n=56) or with radiosurgery (26 Gy; n=30). The pattern and sequence of pulmonary injury and of tumor response was evaluated in 346 follow-up CT studies, 4.9 on average. RESULTS: Symptomatic pneumonitis was observed in 10% after a median interval of 5 months. No pulmonary reaction was observed in most patients 6 weeks after treatment; spotted-streaky condensations were characteristic between 3 months and 6 months. Dense consolidation and retraction started after 9 months and the fibrotic remodelling process continued for years. Ten targets relapsed after a median of 7 months. At 12 months complete response was seen in 43% and the differentiation of residual tumor from pulmonary reaction was not possible in 33%. CONCLUSIONS: A typical sequence of pulmonary reactions was observed without differences between hypofractionated treatment and radiosurgery. Onset of pneumonitis was later compared to conventionally fractionated radiotherapy.

3-D conformal treatment of prostate cancer to 74 Gy vs. high-dose-rate brachytherapy boost: a cross-sectional quality-of-life survey.

The effects of two modalities of dose-escalated radiotherapy on health-related quality of life (HRQOL) were compared. Forty-one consecutive patients were treated with a 3-D conformal (3-DC) boost to 74 Gy, and 43 with high-dose rate (HDR) brachytherapy boost (2x9 Gy), following 3-D conformal treatment to 46 Gy. Median age was 70 years in both groups, median initial PSA was 7.9 microg/l in 3-DC boost patients and 8.1 microg/l in HDR boost patients. Stage was or=7 in 52% and 47%, respectively. HRQOL was assessed cross-sectionally using EORTC QLQ-C30 and organ-specific PR25 modules 3--32 (median 19) and 4--25 (median 14) months after treatment, respectively. Questionnaires were completed by 93% and 97% of patients, respectively. Diarrhea and insomnia scores were significantly increased in both groups. In the PR25 module, scores of 3-DC boost and HDR boost patients for urinary, bowel and treatment-related symptoms were similar. Among responders, 34% of 3-DC boost patients and 86% of HDR boost patients had severe erectile problems. Dose escalation in prostate cancer by either 3-DC boost to 74 Gy or HDR brachytherapy boost appears to result in similar HRQOL profiles.

Oral vinorelbine and cisplatin with concomitant radiotherapy in stage III non-small cell lung cancer (NSCLC): a feasibility study.

BACKGROUND: Concurrent chemoradiotherapy has improved survival in inoperable stage III non-small cell lung cancer (NSCLC). This phase I trial was performed in order to establish a dose recommendation for oral vinorelbine in combination with cisplatin and simultaneous radiotherapy. PATIENTS AND METHODS: Previously untreated patients with stage IIIB NSCLC received concurrent chemoradiotherapy with 66 Gy and 2 cycles of cisplatin and oral vinorelbine which was administered at 3 different levels (40, 50 and 60 mg/m2). This was to be followed by 2 cycles of cisplatin/ vinorelbine oral consolidation chemotherapy. The study goal was to determine the maximal recommended dose of oral vinorelbine during concurrent treatment. RESULTS: 11 stage IIIB patients were entered into the study. The median radiotherapy dose was 66 Gy. Grade 3-4 toxicity included neutropenia, esophagitis, gastritis and febrile neutropenia. The dose-limiting toxicity for concurrent chemoradiotherapy was esophagitis. 9 patients received consolidation chemotherapy, with neutropenia and anemia/thrombocytopenia grade 3 being the only toxicities. The overall response was 73%. CONCLUSION: Oral vinorelbine 50 mg/m2 (days 1, 8, 15 over 4 weeks) in combination with cisplatin 20 mg/m2 (days 1-4) is the recommended dose in combination with radiotherapy (66 Gy) and will be used for concurrent chemoradiotherapy in a forthcoming phase III trial testing the efficacy of consolidation chemotherapy in patients not progressing after chemoradiotherapy.

Hyperfractionated accelerated radiotherapy in combination with weekly cisplatin for locally advanced head and neck cancer.

BACKGROUND: The purpose of this study was to determine the feasibility and efficacy of hyperfractionated accelerated radiotherapy (HFRCB) combined with simultaneous chemotherapy with weekly cisplatin (CDDP) in locally advanced inoperable head and neck cancer. METHODS: From August 1999 to December 2002, 37 patients (median age, 59 years) with Union Internationale Contre le Cancer stage III (n = 2) and stage IV (n = 35) squamous cell cancer of the oropharynx and hypopharynx were treated in a prospective phase I/II trial. Concomitant boost radiotherapy (1.8 Gy, days 1-38 and 1.5 Gy boost, days 22-38, twice daily with at least a 6-hour interval; total dose 69.9 Gy) and simultaneous cisplatin, 40 mg/m2 weekly, were given. RESULTS: The median treatment duration was 42 days (range, 38-46 days). Toxicity was manageable, with neutropenia grade III/IV and thrombocytopenia grade IV in seven and one patients, and mucositis grade III/ IV in 27 and five patients, respectively. Chemotherapy was restricted to four weekly applications in 29 patients mainly because of mucosal toxicity with a median dose intensity of 160 mg/m2 (0-200) of cisplatin in 5.5 weeks. With a median follow-up of 28 months for living patients, the 2-year overall survival rate was 67%. The median overall and relapse-free survival times were 36 and 31 months, respectively. CONCLUSION: HFRCB in combination with weekly cisplatin achieves a high rate of locoregional control and survival. Four weekly cycles of 40 mg/m2 cisplatin seem to be the dose limit for most patients.

How can we further improve radiotherapy for stage-III non-small-cell lung cancer?

Combined modality treatment in advanced NSCLC has produced some gain in treatment outcome. Local control as addressed by radiotherapy is still a significant site of failure. Doses higher than achieved by conventional conformal radiotherapy are shown to result in better control rates. Volume restriction seems to be the most important issue in dose escalation. Integration of PET imaging into target definition, omission of clinically uninvolved lymph-node areas and measures to decrease set-up and movement uncertainties are explored. Introduction of risk estimation based on dose-volume analysis for dose prescription may further optimise individual treatment.

[Present status of treatment in nasopharyngeal carcinoma?]. / Wo stehen wir bei der Behandlung des Nasopharynxkarzinoms?

AIM: Review of the evolution of combined treatment strategies in nasopharyngeal carcinoma. RESULTS: Radiotherapy is accepted standard for treatment of nasopharyngeal cancer. Nevertheless, there is no uniform opinion with regard to doses, fractionation, technique or use of systemic chemotherapy. It is hardly possible to compare the results of recent and historical trials because of different staging systems and because nasopharyngeal cancer occurring in the Oceano-Asian region are biologically different to those in Western countries. Conclusions drawn from former, mostly retrospective analyses are not applicable to newer standards regarding the developments in diagnostics and therapy. Presently simultaneous chemoradiotherapy is standard for lymph node positive nasopharyngeal cancer. CONCLUSIONS: It will be necessary to treat patients with different histologic subtypes with an uniform treatment schedule to define the place of combined modality treatment. This will probably be the only way to develop treatment concepts for distinct stages and biological entities.