This systematic review addressed the following key questions on managing small cell lung cancer (SCLC): the sequence, timing, and dosing characteristics of primary thoracic radiotherapy (TRTx) for ...limited-stage disease; primary TRTx for extensive-stage disease; effect of prophylactic cranial irradiation (PCI); positron emission tomography (PET) for staging; treatment of mixed histology tumors; surgery; and second-line and subsequent-line treatment for relapsed/progressive disease.
The review methods were defined prospectively in a written protocol. We primarily sought randomized controlled trials that compared the interventions of interest.
Robust evidence was lacking for all questions except PCI, for which a patient-level metaanalysis showed that PCI improves survival of SCLC patients who achieved complete response after primary therapy from 15.3 to 20.7% (p = 0.01). The case for concurrent over sequential radiation delivery rests largely on a single multicenter trial. Support for early concurrent therapy comes from one multicenter trial, but two other multicenter trials found no advantage. Metaanalysis did not find significant reductions in 2-year and 3-year mortality rates for early TRTx. Favorable results from a single-center trial on TRTx for extensive stage disease need replication in a multicenter setting. Relevant comparative studies were nonexistent for management of mixed histology disease and surgery for early limited SCLC. PET may be more sensitive in detecting extracranial disease than conventional staging modalities, but studies were of poor quality.
PCI improves survival among those with a complete remission to primary therapy. A research agenda is needed to optimize the effectiveness of TRTx and its components.
To prospectively evaluate the feasibility of delivering 70 Gy once-daily thoracic radiotherapy (TRT), concurrent with chemotherapy, in the treatment of limited-stage small-cell lung cancer (L-SCLC).
...Eligible patients received two cycles of induction paclitaxel (175 mg/m
2 on Day 1) and topotecan (1 mg/m
2 on Days 1–5) with granulocyte colony stimulating factor support, followed by three cycles of carboplatin (area under the curve = 5 on Day 1) and etoposide (100 mg/m
2 on Days 1–3). TRT (70 Gy, 2 Gy/fx/7 weeks) was initiated with the first cycle of carboplatin and etoposide. Prophylactic cranial irradiation was offered to patients achieving a complete response or good partial response.
Ninety percent of patients (57 of 63) proceeded to protocol TRT. There was one treatment-related fatality. Nonhematologic Grade 3/4 toxicities affecting more than 10% of patients, during or after TRT, were dysphagia (16%/5%) and febrile neutropenia (12%/4%). The response rate to all therapy was 92% and the median overall survival is 22.4 months (95% confidence interval 16.1, ∞). Twenty-eight patients remain alive with a median follow-up of 24.7 months.
70 Gy once-daily TRT can be delivered safely in the cooperative group setting for patients with L-SCLC. Initial efficacy data are encouraging. The hypothesis that high-dose once-daily TRT results in comparable or improved survival compared with twice-daily accelerated TRT warrants testing in a Phase III trial.
The thrill of victory; the agony of defeat Turrisi, 3rd, Andrew T
International journal of radiation oncology, biology, physics,
04/2008, Letnik:
70, Številka:
5
Journal Article
Background: Despite advances in early detection and effective treatment, cancer remains one of the most feared diseases. Among the most common side effects of cancer and treatments for cancer are ...pain, depression, and fatigue. Although research is producing increasingly hopeful insights into the causes and cures for cancer, efforts to manage the side effects of the disease and its treatments have not kept pace. The challenge that faces us is how to increase awareness of the importance of recognizing and actively addressing cancer-related distress. The National Institutes of Health (NIH) convened a State-of-the-Science Conference on Symptom Management in Cancer: Pain, Depression, and Fatigue to examine the current state of knowledge regarding the management of pain, depression, and fatigue in individuals with cancer and to identify directions for future research. Specifically, the conference examined how to identify individuals who are at risk for cancer-related pain, depression, and/or fatigue; what treatments work best to address these symptoms when they occur; and what is the best way to deliver interventions across the continuum of care. State- of-the-Science Process: A non-advocate, non-Federal, 14-member panel of experts representing the fields of oncology, radiology, psychology, nursing, public health, social work, and epidemiology prepared the statement. In addition, 24 experts in medical oncology, geriatrics, pharmacology, psychology, and neurology presented data to the panel and to the conference audience during the first 1.5 days of the conference. The panel then prepared its statement, addressing the five predetermined questions and drawing on submitted literature, the speakers' presentations, and discussions held at the conference. The statement was presented to the conference audience, followed by a press conference to allow the panel to respond to questions from the media. After its release at the conference, the draft statement was made available on the Internet. The panel's final statement is available at http://consensus.nih.gov. Conclusions: The panel concluded that the available evidence supports a variety of interventions for treating cancer patients' pain, depression, and fatigue. Clinicians should routinely use brief assessment tools to ask patients about pain, depression, and fatigue and to initiate evidence-based treatments. Assessment should include discussion about common symptoms experienced by cancer patients, and these discussions should continue over the duration of the illness. Impediments to effective symptom management in cancer patients can arise from different sources and interactions among providers, patients and their families, and the health care system. Numerous factors could interfere with adequate symptom management. Among these factors are incomplete effectiveness of some treatments, a lack of sufficient knowledge regarding effective treatment strategies, patient reluctance to report symptoms to caregivers, a belief that such symptoms are simply a part of the cancer experience that must be tolerated, and inadequate coverage and reimbursement for some treatments. Additional research is needed on the definition, occurrence, the treatment of pain, depression, and fatigue, alone and in combination, in adequately funded prospective studies. The panel also concluded that the state of the science in cancer symptom management should be reassessed periodically.
Tumor control probability (TCP) model calculations may be used in a relative manner to evaluate and optimize three-dimensional (3-D) treatment plans. Using a mathematical model which makes a number ...of simplistic assumptions, TCPs can be estimated from a 3-D dose distribution of the tumor given the dose required for a 50% probability of tumor control (
D
50) and the normalized slope (
γ) of the sigmoid-shaped dose–response curve at
D
50. The purpose of this work was to derive
D
50 and
γ from our clinical experience using 3-D treatment planning to treat non-small cell lung cancer (NSCLC) patients. Our results suggest that for NSCLC patients, the dose to achieve significant probability of tumor control may be large (on the order of 84 Gy) for longer (>30 months) local progression-free survival.
Purpose: The influence of treatment parameters, such as (a) fraction size and (b) average and maximum dose (as derived from three-dimensional (3D) distributions), on the incidence of pericarditis was ...analyzed. To understand and predict the dose and volume effect on the pericardium, a normal tissue-complication probability model was tested with these complication data.
Methods and Materials: Patients (
n
= 57) entered in 3 consecutive University of Michigan protocols of combined modality for treatment of localized esophageal carcinoma, and having 3D treatment planning for radiation therapy were the subject of this study. Univariate and multivariate analyses were performed to determine the significance of the effect of fraction size and dose parameters on the development of any grade of pericarditis. Dose distributions were corrected for the biological effect of fraction size using the linear-quadratic method. Normal tissue complication probability (NTCP) was calculated with the Lyman model.
Results: Nonmalignant pericardial effusions occurred in 5 of the 57 patients; all effusions were in patients who received treatment with 3.5 Gy daily fractions. On multivariate analysis, no dose factor except fraction size predicted pericarditis, until the dose distributions were corrected for the effect of fraction size (“bio”-dose). Then, both “bio-average” and “bio-maximum” dose were significant predictive factors (
p
= 0.014). NTCPs for the patients with pericarditis range from 62% to 99% for the calculations with the “bio”-dose distributions vs. 0.5% to 27% for the uncorrected distributions.
Discussion: A normal tissue complication probability (NTCP) model predicts a trend towards a high incidence of radiation pericarditis for patients who have high complication probabilities. It is important to correct the dose distribution for the effects of fractionation, particularly when the fraction size deviates greatly from standard (2.0 Gy) fractionation.
Purpose
The aim of this study was to compare toxicities, disease control, survival outcomes, and patterns of failure between groups of limited-stage small-cell lung cancer patients treated with ...once-daily versus twice-daily radiotherapy and concurrent chemotherapy.
Materials and methods
This single-institution retrospective analysis included a comparison of two of radiotherapy regimens to planned doses of (1) ≥59.4 Gy at 1.8–2.0 Gy per once-daily fraction or (2) ≥45 Gy at 1.5 Gy per twice-daily fractions with concurrent platinum-based chemotherapy. Comparative analyses of toxicities and disease control were performed.
Results
A total of 71 patients were included in the present study (17 once-daily, 54 twice-daily). Patient, tumor, staging, and treatment factors were similar between the two treatment groups. Median planned radiotherapy doses were 60 Gy (range 59.4–70.0 Gy) and 45 Gy (range 45–51 Gy) for the once-daily and twice-daily groups, respectively. Acute toxicities were similar between the groups (∼20% grade 3 esophagitis). At a median survival follow-up of 26.2 months (range 3.4–85.5 months), 42 patients had died. The 2-year overall survival estimates were similar at 43% and 49% for the once-daily versus twice-daily groups, respectively. Isolated in-field failures were similar between the two groups (∼17%).
Conclusion
The present analysis did not detect a statistically significant difference in acute toxicities, disease control, or survival outcomes in limited-stage small-cell lung cancer patients treated with concurrent chemotherapy and once-daily versus twice-daily radiotherapy.
Purpose: To determine acute and late complications for bladder and rectum and to determine dose–volume correlations.
Methods and materials: Sixty-four patients received definitive treatment for ...prostate cancer between January 1995 and December 1998 using conformal three-dimensional radiotherapy. Doses ranged from 72 to 80
Gy. The acute and late side effects were gathered retrospectively, and graded according to Radiotherapy and Oncology Group criteria (RTOG). The patients were divided into two groups: ≤72
Gy (Group A) and ≥76
Gy (Group B) and had a mean follow-up of 32 and 22 months, respectively.
Results: No grades 3–4 acute, urinary or rectal toxicity was reported. Acute grade 2 rectal complications were seen in 10 and 18% of the patients in Groups A and B, respectively. They were observed at a mean dose of 38
Gy. Acute grade 2 urinary symptoms were 33 and 47% for Groups A and B, respectively. They were seen at a mean dose of 43
Gy. Acute rectal symptoms were dose–volume related. Patients without diarrhea had a mean rectal volume receiving a dose of 70
Gy or more of 8.5
cm
3. However, patients with RTOG 2 diarrhea had a volume of 16.5
cm
3 (
P=0.042). No dose–volume relationship for acute bladder symptoms or late complications were seen. Grades 1–2 late rectal and bladder complications were seen in 11 and 8% of the patients, respectively. None required hospital admission or transfusion.
Conclusion: Radiotherapy to the prostate can be given at 80
Gy. No grades 3–4 acute, urinary or rectal toxicity was reported. Acute rectal symptoms are dose–volume related.
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