Frontiers of Radiation Therapy and Oncology最新文献

In spite of the developments in chemo- and radiotherapy, surgery remains the mainstay of curative treatment of early stage non-small cell lung cancer (NSCLC). In stage Ia/Ib (T1, T2, N0), NSCLC lobectomy offers the best chance for cure, yielding survival rates of between 58 and 76%. Since the extent of mediastinal lymph node dissection does not seem to play a major prognostic role in stage Ia, video-thoracoscopic lobectomy yields equally good results as the open approach. Due to the necessity for a small thoracotomy when harvesting the specimen and the time-consuming lymph-node dissection minimally invasive lobar resections have failed to become routinely used. Minor resections, though sometimes necessary from the functional point of view, have a lower curative potential. They yield the best results if applied in tumors measuring less than 2 cm. Stage II, characterized by involvement of the N1-position and/or a more central tumor growth, has a 5-year survival of 45-52% and requires treatment by lobectomy or pneumonectomy. Sleeve resection may obviate the need for pneumonectomy in central upper-lobe tumors. In interlobar N1, however, pneumonectomy is indicated from the oncological point of view, since even meticulous lymph-node dissection is unable to achieve tumor control in this situation.

Limited disease small cell lung cancer (LD-SCLC) is a heterogeneous disease, not only for its clinical behavior, but also for is anatomical extension. In very rare, early cases, LD-SCLC might be treated with surgery and chemotherapy, but as the overwhelming majority of patients present with locally advanced disease, the standard of care is concurrent chest radiotherapy with cisplatin and etoposide chemotherapy followed by prophylactic cranial irradiation (PCI). Newer chemotherapeutic drugs as well as targeted agents have not improved the outcome thus far. Given concurrently with chest irradiation, cisplatin combined with etoposide, administered every 21 days for 4-5 cycles have frequently been used. Thoracic radiotherapy should begin as early as possible during the first chemotherapy cycle. A total radiation dose of 45 Gy is recommended, delivered in a short overall treatment time (less than 4 weeks). Accelerated therapy increased absolute 5-year survival rates by 10% compared to longer treatment times, at the expense of an incidence of severe esophagitis of approximately 30%, which is reversible within a few weeks. Hematological complications and late pulmonary damage may occur, but is not more frequent than with less intensive schedules that impair long-term survival. Obviously, patient selection is crucial. Because after combined chemotherapy and thoracic radiotherapy, the remission status of the tumor is difficult to assess because of radiation-induced radiographic changes, patients that show no tumor progression are suitable for PCI. With this treatment, 5-year survival rates of 25% can be achieved in patients with LD-SCLC.

Small cell lung cancer is an aggressive form of lung cancer with a poor prognosis. Most patients present with extensive stage of the disease. To reduce the high risk of brain metastases, prophylactic cranial irradiation has been shown to be very effective. Prophylactic cranial irradiation should now routinely be used for all patients who have responded to chemotherapy. Thoracic radiotherapy is often reserved for palliation. However, the high incidence of residual disease after chemotherapy and the reported beneficial effect of radiotherapy in a single study has led to two clinical trials which will soon open and address the question whether thoracic radiotherapy also has a role in responding patients with extensive stage small cell lung cancer.

Adjuvant radiotherapy following radical surgery in NSCLC has long been a matter of debate. The pros and cons have all been discussed thoroughly and the data existing due to their partial outdated nature in respect of the diagnostic and therapeutic maneuvers used make it difficult to rely on them. Based on the existing level of evidence from randomized studies, the decision to irradiate a NSCLC patient postoperatively does not seem to be prudent, as several meta-analyses in fact have rather shown a detrimental effect than any benefit. As the majority of the randomized trials that are the bases of the meta-analyses are neither of good quality nor include those patients that are nowadays regarded as those for whom adjuvant irradiation should be discussed, other sources of information are of relevance. Subanalyses of randomized phase III trials and recently published SEER data are indicative that there is a benefit from adjuvant irradiation not only in terms of freedom from local failure but of overall survival as well. Notably, this is not at the expense of unacceptably high rates of long-term side effects.

For patients with early (stage I/II) non-small cell lung cancer (NSCLC) surgery is considered as the standard treatment of choice, although recent data on additional chemotherapy (CHT) showed that it may be beneficial in this setting. There is, however, a subset of patients that never undergo surgery. These patients are considered technically operable, but medically inoperable, due to existing comorbidities. In addition, frequently elderly patients with early NSCLC are denied surgery due to expected peri- and/or postoperative complications. Finally, in recent years there has been an increase in the incidence of patients refusing surgery. For all these patients, radiation therapy (RT) was traditionally considered as the standard treatment option. Data accumulated over the last 5 decades showed that RT alone can produce median survival times of up to > 30 months and 5-year survival of up to 30%. When cancer-unrelated deaths were taken into account, cause-specific survival rates were usually higher for some 10-15%. Accumulated experience seems to suggest that doses of at least 65 Gy with standard fractionation or its equivalent when altered fractionation is used are necessary for control of the disease. Smaller tumors seem to have favorable prognosis, while the issue of elective nodal RT continues to be controversial. Patterns of failure have clearly identified local failure as the predominant one. Although a number of potential pretreatment patient- and tumor-related prognostic factors have been examined, none has been shown to clearly influenced survival. Toxicity was usually low.

Some studies have shown that a number of patients with positive lymph nodes may be potentially curable. Seventy-five lymph node-positive prostate cancer patients were treated by radiotherapy alone (36%) or by radiotherapy after radical prostatectomy (64%). The prostatic region was irradiated in 20 patients (27%) and the prostatic region plus pelvic lymph nodes in 55 (73%). The median lymph node dose was 46 Gy, the median dose at the prostatic region 67 Gy. Biochemical no evidence of disease (bNED), overall survival as well as acute/late gastrointestinal and urogenital side effects were evaluated. Median follow-up was 40 months (range 1-132). Five- and eight-year bNED rates were 54% and 51%, respectively; 5- and 8-year overall survival rates were 78% and 67%, respectively. Concerning bNED and overall survival, no significant difference in regard to treatment technique (prostatic region vs. prostatic region plus pelvic lymph nodes) or treatment strategy (radical prostatectomy plus radiotherapy vs. radiotherapy alone) was found. Four of seventy-five patients showed no prostate-specific antigen progression after 9 years. Acute/late gastrointestinal and urogenital side effects were mostly moderate, revealing no difference in severity regarding treatment technique. To conclude, advanced treatment techniques allowing dose escalation in the prostatic and pelvic region should be considered in selected lymph node-positive prostate cancer patients in order to further improve clinical outcome.

Background: Within 5 years following radical prostatectomy, between 15 and 60% of patients with pT3 prostate carcinomas show an increasing prostate-specific antigen (PSA) level as a sign of local and/or systemic tumor progression. Apart from a large number of retrospective investigations, results are available from 3 randomized studies.

Results: For pT3 prostate carcinomas, the data from the 3 randomized studies agree, showing a reduced biochemical progression rate after 4-5 years of around 20%. The majority of authors use total doses of 60 Gy with single doses of 2 Gy. The rate of severe late side effects is below 2%. The data for pT2 prostate carcinomas with positive margins are worse. Here, controversy exists, and further investigations are required.

Conclusions: The effectiveness of adjuvant radiotherapy for patients with pT3 tumors with positive margins with and without undetectable PSA levels is proposed. However, a survival advantage has not been demonstrated to date. For patients with positive margins in organ-limited prostate carcinomas (pT2 R1), randomized studies are recommended. It is unclear whether adjuvant radiotherapy is superior to radiotherapy for PSA levels rising out of the undetectable range after radical prostatectomy.

Prednisolone monotherapy has been the standard systemic treatment in many patients with androgen- independent prostate cancer and should today be compared to treatment with Taxotere plus prednisolone. One hundred and thirty four patients were entered into a randomized phase II study [arm A: Taxotere plus prednisolone (30 mg/m2 weekly during 5 of 6 weeks + prednisolone 5 mg orally twice daily); arm B: prednisolone (5 mg orally twice daily)]. Biochemical response at 6 weeks was the primary outcome parameter, with progression-free and overall survival as secondary outcomes. Biochemical response at 6 weeks was recorded in 29 of 54 evaluable patients in arm A [54%; 95% confidence interval (CI) 40-67%] and 13 of 50 patients in arm B (26%; 95% CI 14-38%), with a similar difference in response rates at 12 weeks. Median progression-free survival was 11 months in arm A (95% CI 5.8-16.2)and 4 months in arm B (95% CI 2.4-5.6). Median overall survival was 27 months in arm A (95% CI 19.8-34.1) and 18 months in arm B (95% CI 15.2-20.8). Assessment of pain and quality of life showed superiority of arm A treatment, without unacceptable toxicity. Taxotere plus prednisolone is recommended as systemic standard treatment in androgen-independent prostate cancer.

Lymph node status in prostate cancer is not only of prognostic but also of tremendous therapeutic relevance. In case of positive lymph nodes (N+), common standards demand the renunciation of local curative therapy (such as radiotherapy or radical prostatectomy) and hormonal withdrawal, or an appropriate adjuvant therapy can be planned (for example, early androgen ablation). But none of the currently available means of radiologic imaging (CT, MRT, PET-CT) provides sufficient identification of lymph node (micro)metastases (< 5 mm). Also, predictive nomograms which are based on data from limited pelvic lymph node dissection (PLND) do not offer a sufficient grade of reliability. However, the limitation of the dissection area results in missing about 50-60% of N+ patients. In addition, the preoperative diagnostics often underestimate the true pathological stage. Presently, it seems that only the histological detection of lymph node metastases by methods with high sensitivity, like sentinel lymph node dissection or extended PLND, are suitable for lymph node staging in prostate cancer. The disadvantages of extended PLND are a high operative effort and increased complication rate. Therefore, sentinel lymph node dissection seems to strike a balance between high sensitivity and low complication rate.

The proper management of prostate cancer is dependent on appropriate risk categorization, based on pretreatment prostate-specific antigen (PSA), clinical stage and Gleason score (GS). The use of radiotherapy in low-risk (T1-T2a, PSA < 10 ng/ml and GS 20 ng/ml or GS >or=6 8), radiation with hormones has become the standard treatment. The issues that remain focus on determining the optimal duration of hormones, assessing the use of locoregional dose escalation and determining the possible benefit from adjuvant chemotherapy.