A Systematic Overview of Radiation Therapy Effects in Breast Cancer

A systematic review of radiation therapy trials in several tumour types was performed by The Swedish Council of Technology Assessment in Health Care (SBU). The procedures for evaluation of the scientific literature are described separately (Acta Oncol 2003; 42: 357-365). This synthesis of the literature on radiation therapy for breast cancer is based on data from 29 randomized trials, 6 meta-analyses and 5 retrospective studies. In total, 40 scientific articles are included, involving 41 204 patients. The results were compared with those of a similar overview from 1996 including 285 982 patients. The conclusions reached can be summarized as follows: There is strong evidence for a substantial reduction in locoregional recurrence rate following postmastectomy radiation therapy to the chest wall and the regional nodal areas.There is strong evidence that postmastectomy radiation therapy increases the disease-free survival rate.There are conflicting data regarding the impact of postmastectomy radiotherapy upon overall survival.There is strong evidence that breast cancer specific survival is improved by postmastectomy radiotherapy.There is strong evidence for a decrease in non-breast cancer specific survival after postmastectomy radiotherapy.There is some evidence that overall survival is increased by optimal postmastectomy radiation therapy.There is strong evidence that postmastectomy radiotherapy in addition to surgery and systemic therapy in mainly node-positive patients decreases local recurrence rate and improves survival.There is moderate evidence that the decrease in non-breast cancer specific survival is attributed to cardiovascular disease in irradiated patients.There are conflicting data whether breast conservation surgery plus radiotherapy is comparable to modified radical mastectomy alone in terms of local recurrence rate.There is strong evidence that breast conservation surgery plus radiotherapy is comparable to modified radical mastectomy alone in terms of disease-free survival and overall survival.There is strong evidence that postoperative radiotherapy to the breast following breast conservation surgery results in a statistically and clinically significant reduction of ipsilateral breast recurrences followed by diminished need for salvage mastectomies.There is strong evidence that the omission of postoperative radiotherapy to the breast following breast conservation surgery has no impact on overall survival. In one meta-analysis including three randomized studies a survival advantage is demonstrated by Bayesian statistics.There is strong evidence that the addition of a radiation boost after conventional radiotherapy to the tumour bed after breast conservation surgery significantly decreases the risk of ipsilateral breast recurrences but has no impact on overall survival after short follow-up.There is strong evidence for the use of postoperative radiotherapy to the breast following breast conservation surgery for DCIS (ductal breast cancer in situ). Radiotherapy leads to a clinically and statistically significant reduction of both non-invasive and invasive ipsilateral breast recurrences.There is insufficient evidence to define the optimal integration of systemic adjuvant therapy and postoperative radiotherapy.There are limited data on radiotherapy-related morbidity in breast cancer. No conclusions can be drawn.     

A systematic overview of radiation therapy effects in breast cancer

A systematic review of radiation therapy trials in several tumour types was performed by The Swedish Council of Technology Assessment in Health Care (SBU). The procedures for evaluation of the scientific literature are described separately (Acta Oncol 2003; 42: 357-365). This synthesis of the literature on radiation therapy for breast cancer is based on data from 29 randomized trials, 6 meta-analyses and 5 retrospective studies. In total, 40 scientific articles are included, involving 41 204 patients. The results were compared with those of a similar overview from 1996 including 285 982 patients. The conclusions reached can be summarized as follows: There is strong evidence for a substantial reduction in locoregional recurrence rate following postmastectomy radiation therapy to the chest wall and the regional nodal areas. There is strong evidence that postmastectomy radiation therapy increases the disease-free survival rate. There are conflicting data regarding the impact of postmastectomy radiotherapy upon overall survival. There is strong evidence that breast cancer specific survival is improved by postmastectomy radiotherapy. There is strong evidence for a decrease in non-breast cancer specific survival after postmastectomy radiotherapy. There is some evidence that overall survival is increased by optimal postmastectomy radiation therapy. There is strong evidence that postmastectomy radiotherapy in addition to surgery and systemic therapy in mainly node-positive patients decreases local recurrence rate and improves survival. There is moderate evidence that the decrease in non-breast cancer specific survival is attributed to cardiovascular disease in irradiated patients. There are conflicting data whether breast conservation surgery plus radiotherapy is comparable to modified radical mastectomy alone in terms of local recurrence rate. There is strong evidence that breast conservation surgery plus radiotherapy is comparable to modified radical mastectomy alone in terms of disease-free survival and overall survival. There is strong evidence that postoperative radiotherapy to the breast following breast conservation surgery results in a statistically and clinically significant reduction of ipsilateral breast recurrences followed by diminished need for salvage mastectomies. There is strong evidence that the omission of postoperative radiotherapy to the breast following breast conservation surgery has no impact on overall survival. In one meta-analysis including three randomized studies a survival advantage is demonstrated by Bayesian statistics. There is strong evidence that the addition of a radiation boost after conventional radiotherapy to the tumour bed after breast conservation surgery significantly decreases the risk of ipsilateral breast recurrences but has no impact on overall survival after short follow-up. There is strong evidence for the use of postoperative radiotherapy to the breast following breast conservation surgery for DCIS (ductal breast cancer in situ). Radiotherapy leads to a clinically and statistically significant reduction of both non-invasive and invasive ipsilateral breast recurrences. There is insufficient evidence to define the optimal integration of systemic adjuvant therapy and postoperative radiotherapy. There are limited data on radiotherapy-related morbidity in breast cancer. No conclusions can be drawn.     

A systematic overview of radiation therapy effects in prostate cancer

A systematic review of radiation therapy trials in prostate cancer has been performed according to principles adopted by the Swedish Council of Technology Assessment in Health Care (SBU). This synthesis of the literature is based on data from one meta-analysis, 30 randomized trials, many dealing with hormonal therapy, 55 prospective trials, and 210 retrospective studies. Totally the studies included 152,614 patients. There is a lack of properly controlled clinical trials in most important aspects of radiation therapy in prostate cancer. The conclusions reached can be summarized as follows: * There are no randomized studies that compare the outcome of surgery (radical prostatectomy) with either external beam radiotherapy or brachytherapy for patients with clinically localized low-risk prostate cancer. However, with the advent of widely accepted prognostic markers for prostate cancer (pre-treatment PSA, Gleason score, and T-stage), such comparisons have been made possible. There is substantial documentation from large single-institutional and multi-institutional series on patients with this disease category (PSA < 10, GS < or = 6, < or = T2b) showing that the outcome of external beam radiotherapy and brachytherapy is similar to those of surgery. * There is fairly strong evidence that patients with localized, intermediate risk, and high risk (pre-treatment PSA > or = 10 and/or GS > or = 7 and/or > T2) disease, i.e. patients normally not suited for surgery, benefit from higher than conventional total dose. No overall survival benefit has yet been shown. * Dose escalation to patients with intermediate-risk or high-risk disease can be performed with 3D conformal radiotherapy (photon or proton) boost, with Ir-192 high dose rate brachytherapy boost, or brachytherapy boost with permanent seed implantation. Despite an increased risk of urinary tract and/or rectal side effects, dose-escalated therapy can generally be safely delivered with all three techniques. * There is some evidence that 3D conformal radiotherapy results in reduced late rectal toxicity and acute anal toxicity compared with radiotherapy administered with non-conformal treatment volumes. * There is some evidence that postoperative external beam radiotherapy after radical prostatectomy in patients with pT3 disease prolongs biochemical disease-free survival and that the likelihood of achieving long-term DFS is higher when treatment is given in an adjuvant rather than a salvage setting. A breakpoint seems to exist around a PSA level of 1.0 ng/mL, above which the likelihood for eradication of the recurrence of cancer diminishes. * After prostatectomy, endocrine therapy prior to and during adjuvant radiotherapy may result in longer biochemical disease-free survival than if only adjuvant radiotherapy is given. No impact on overall survival has been shown. * There is fairly strong evidence that short-term endocrine therapy prior to and during radiotherapy results in increased disease-free survival, increased local control, reduced incidence of distant metastases, and reduced cause-specific mortality in patients with locally advanced disease. * There is some evidence that short-term endocrine therapy prior to and during radiotherapy results in increased overall survival in a subset (GS 2-6) of patients with locally advanced disease. * There is strong evidence that adjuvant endocrine treatment after curative radiotherapy results in improved local control, increased freedom from distant metastases, and increased disease-free survival in patients with loco-regionally advanced and/or high-risk disease. * There is moderately strong evidence that adjuvant endocrine treatment after radiotherapy results in longer overall survival compared with radiotherapy alone in patients with loco-regionally advanced disease.     

Postoperative radiotherapy in stage II or IIIA completely resected non-small cell lung cancer: a systematic review and practice guideline

The Lung Cancer Disease Site Group of Cancer Care Ontario's Program in Evidence-based Care conducted a systematic review of literature published between 1985 and July 2003 and developed an evidence-based clinical practice guideline on postoperative radiotherapy in patients with completely resected pathologic stage II or IIIA non-small cell lung cancer (NSCLC). Forty-four Ontario clinicians reviewed the draft guideline. Evidence included one meta-analysis of individual patient data (from nine randomized controlled trials) and three randomized controlled trials (two including data reported in the meta-analysis) that compared surgery with or without postoperative radiotherapy. The meta-analysis and one trial detected a significant detriment to survival with postoperative radiotherapy. Two trials detected no survival difference. The meta-analysis detected a significant advantage in local recurrence-free survival (time to local recurrence or death) with surgery alone, although two trials detected a significant advantage in rate of local recurrence with postoperative radiotherapy. Subset analyses from the meta-analysis and one trial suggested that postoperative radiotherapy was detrimental to survival mainly in stage II disease; no benefit or detriment was evident for stage III disease. Recommendations: Postoperative radiation therapy following complete resection of stage II non-small cell lung cancer is not recommended. No definitive recommendation can be made for stage IIIA disease.     

食管癌术后患者放化疗临床应用研究进展

手术治疗为食管癌患者的主要治疗方式之一,但单纯手术治疗并未使食管癌患者取得令人满意的结果,其主要的失败模式及死亡原因为区域性复发和远处转移,研究表明术后辅助性治疗是提高患者局部控制率及生存率的关键,但什么样的患者真正能从术后辅助性放化疗中受益,在目前并无统一结论。本文简要总结了目前不同食管癌术后患者接受辅助性放化疗的研究结果,并分析了照射野的范围及术后辅助性放化疗后的失败模式。     

Local therapy and survival in breast cancer with distant metastases

This review article presents an evaluation of the effects of local therapy on survival of breast cancer patients with distant metastases along with a discussion of their relevance. Primary and recurrent breast cancers with distant metastases are systemic diseases with poor prognosis. However, several retrospective studies have demonstrated that surgical removal of the primary breast tumor has a favorable impact on the prognosis of stage IV breast cancer patients. Similarly, it has been reported that surgical resection of metastatic lesions in the lung as well as the liver yields unexpectedly promising results. The interaction of local treatment and systemic therapy may be important, because surgery and radiotherapy are only local treatments. However, it remains uncertain whether these encouraging findings are due to the surgical procedure itself or preoperative patient selection. Only a randomized prospective study can definitively show whether local treatment can prevent death from stage IV disease or recurrent breast cancer with distant metastases. Until data from prospective studies are available, clinicians must weigh retrospective experiences and clinical judgment in deciding whether to offer surgery or radiotherapy to these patients.     

Radiothérapie et sarcomes des tissus mous

Since the Rosenberg studies of 1982, soft tissue sarcoma in the extremities has been treated with conservative surgery and postoperative radiotherapy. Two randomized trials highlight the benefit of postoperative radiotherapy to local control. No advantage in survival after radiotherapy has been established. For retroperitoneal, head and neck, breast and trunk sarcoma, the effectiveness of radiotherapy has not been demonstrated, although a number of retrospective studies have indicated the beneficial aspects of this treatment modality. Radiation therapy will never replace surgery. After complete surgery, the dose of radiation is usually 50 Gy, but, in the case of residual disease, doses greater than 64 Gy are appropriate. New radiation technologies have become very useful in treating soft tissue sarcoma.     

The future of adjuvant treatment in gastrointestinal cancer

Adjuvant treatment is based on the concept that surgery is only potentially curative and that apparently localized disease has extended beyond surgical resection or is already disseminated. Although death might be related to local recurrence as well as to disease dissemination, most of the trials have tested only one adjuvant modality. Among many negative and non-contributory studies, very few positive results were obtained: in rectal cancer it seems that pre-operative and perhaps postoperative radiotherapy may reduce the incidence of local recurrences, and in colon cancer patients treated with Methyl-CCNU, vincristine and 5-fluorouracil (5-FU) had a significant increase in survival. In colon cancer, the lack of active drug might at least partly explain negative studies, but in gastric cancer the most active combination in advanced disease has failed to demonstrate an improvement of survival in the adjuvant setting. Future trials should take account of this succession of negative trials.     

Postoperative radiation therapy for lung cancer: where do we stand?

Lung cancer is the leading cause of cancer mortality in the United States. Local recurrence after surgery for operable disease has long been recognized as a hindrance to long-term survival. Postoperative radiation therapy was logically explored as a means to improve local control and survival. Multiple randomized trials were conducted, many showing improved local control, but none demonstrated a statistically significant survival benefit. In fact, a meta-analysis showed a rather large survival detriment, presumably from treatment-related complications. Radiation therapy has evolved over the years, and more modern treatment planning and delivery has the potential to treat sites deemed at high risk of recurrence while limiting the dose to critical intrathoracic structures, which should decrease the risk of treatment-related complications. Recent studies have supported this supposition. Similarly, since cancer is often a systemic disease, local control will become a more pressing issue as systemic micrometastatic disease is eradicated with effective chemotherapy. Unfortunately, randomized trials testing the effectiveness of modern postoperative radiation therapy in the chemotherapy era have not been performed. Clinicians must therefore counsel patients regarding the risk of disease recurrence after surgery, the potential but unproven benefit of postoperative radiation therapy, and the possibility of treatment-related complications.     

Progress and controversies: Radiation therapy for invasive breast cancer

Answer questions and earn CME/CNE Radiation therapy is a critical component of the multidisciplinary management of invasive breast cancer. In appropriately selected patients, radiation not only improves local control, sparing patients the morbidity and distress of local recurrence, but it also improves survival by preventing seeding and reseeding of distant metastases from persistent reservoirs of locoregional disease. In recent years, considerable progress has been made toward improving our ability to select patients most likely to benefit from radiotherapy and to administer treatment in ways that maximize clinical benefit while minimizing toxicity and burden. This article reviews the role of radiation therapy in invasive breast cancer management, both after breast‐conserving surgery and after mastectomy. It focuses particularly on emerging evidence that helps to define the clinical situations in which radiotherapy is indicated, the appropriate targets of treatment, and optimal approaches for minimizing both the toxicity and the burden of treatment, all in the context of the evolving surgical and systemic management of this common disease. It includes a discussion of new approaches in breast cancer radiotherapy, including hypofractionation and intensity modulation, as well as a discussion of promising avenues for future research. CA Cancer J Clin 2014;64:135–152. ^© 2013 American Cancer Society .     

Results of adjuvant radiation therapy in cancer of the rectum. Thomas Jefferson University Hospital experience

From 1972 to 1981, 174 patients with cancer of the rectum surgically staged as B2 or C disease, underwent surgical resection of the tumors for cure. Eighty-eight patients received surgery only with no further adjuvant therapy, and the remaining 86 patients were treated with a combination of radiation and surgery. Twenty-nine patients received low-dose preoperative radiation (500 rad in one fraction); 26 patients received postoperative radiation (4500 rad in 5 weeks); and 31 patients received combined low-dose preoperative radiation (500 rad) and postoperative radiation (4500 rad in 5 weeks). This experience was analyzed to determine the patterns of failure and the impact of adjuvant therapy on survival. Patients undergoing surgery alone had a 26% incidence of local failure in the pelvis and a 57% incidence of distant metastasis. Patients receiving low-dose preoperative radiation had a reduction in the rate of distant metastasis (24%), but no effect on local failure (34%). On the other hand, patients receiving postoperative radiation had a reduction in the local failure rate (11%), with no effect on distant metastasis (50%). Patients who received the combined preoperative and postoperative treatment had a reduction in both the local recurrence rate (7%), and the rate of distant metastasis (13%), and these patients also had a substantial improvement in survival over surgery alone. Survival of patients undergoing surgery alone was 34% at 5 years and was not substantially different for patients undergoing low-dose preoperative irradiation (48%), or for patients receiving postoperative irradiation (29%). Survival in patients receiving combined preoperative and postoperative irradiation was substantially better (78%) than the other groups of patients.     

Risk Stratification in Ductal Carcinoma in Situ: The Role of Genomic Testing

From the earliest days of conservative surgery for ductal carcinoma in situ (DCIS) of the breast, there have been attempts to identify patients who may not need postoperative radiation. Randomized prospective trials have not identified a population for whom there is no benefit to radiation. However, decades of studies of clinical, radiological and pathologic correlates to local recurrence have led to criteria for a patient subgroup at low risk for local recurrence after omission of radiation. Gene expression profiling for invasive breast cancer has been used to identify patients at low, intermediate or high risk for distant recurrence. Application of this methodology to DCIS aims to identify patients at low, intermediate or high risk for local recurrence. Whether this method of risk stratification will prove more accurate than clinical, radiological and pathologic risk stratification, or identify patients with little to no clinical benefit from radiation, remains to be seen.     

Post-mastectomy radiation in male breast cancer.

BACKGROUND AND PURPOSE: Previous studies of male breast cancer have suggested that due to the lack of breast tissue, post-mastectomy radiation should be routinely utilized in all stages of this disease. We propose that the pattern of local recurrence in male breast cancer is, stage for stage, similar to female breast cancer and, therefore, the indications for post-mastectomy radiation should be similar. MATERIALS AND METHODS: We conducted a retrospective analysis of 44 cases of male breast cancer from 1967 to 1995. Primary therapy was surgical in all cases and 13 patients received postoperative radiation. RESULTS: Tumor, Nodal, Metastasis (TNM) classification revealed 34 Stages I/II and ten Stage III cases. The 5-year overall survival was 75% and the 5-year local recurrence free survival was 70% for the entire group. In patients with Stages I/II disease, 28/34 underwent surgery alone, of whom, at 5-year follow up, only one suffered an isolated local-regional recurrence (3.5%) and one distant failure (3.5%). Of the ten patients with Stage III disease, three underwent surgery alone and none suffered a local failure. While the crude rate of local recurrence (local recurrence at any time in relation to distant failure) for all patients as a whole was 11%, the isolated local recurrence rate (before distant failure) was seen in only 6%, and only 3% amongst those with Stages I/II disease treated with surgery alone. CONCLUSION: Although postoperative radiation is often routinely utilized in all stages of male breast cancer to help decrease the risk of local recurrence, this review suggests that this risk is small, especially in early stage disease, and, therefore, the same indications for post-mastectomy radiation that apply to female breast cancer, should be utilized in males.     

Omission of radiotherapy in elderly patients with early breast cancer: 15-Year results of a prospective non-randomised trial

BackgroundWhether radiotherapy (RT) is beneficial in elderly (⩾70 years) patients undergoing conservative surgery for early breast cancer has long been controversial. Recent randomised trials show that most elderly patients do not benefit from RT. We started a prospective non-randomised trial to address this issue in 1987 and now present results for the 627 consecutive pT1/2cN0 patients recruited, and treated by conservative surgery (quadrantectomy) and tamoxifen, and assigned non-randomly to RT or no RT.MethodsWe used multivariate competing risks models to estimate 15-crude cumulative incidence (CCI) of ipsilateral breast tumour recurrence (IBTR), distant metastasis and breast cancer mortality. The models incorporated a propensity score as a measure of probability of receiving RT based on baseline characteristics, to account for the lack of randomisation.ResultsFor pT1 patients, 15-year CCIs of IBTR, distant metastasis and breast cancer death were indistinguishable in the RT and no RT groups. For pT2 patients, 15-year CCI of IBTR was much higher in those not given RT (14.6% versus 0.8%, p = 0.004), although breast cancer mortality and distant metastasis did not differ significantly between RT and no RT.ConclusionsConsistent with the findings of recent randomised trials, our long-term data indicate that most elderly, ER-positive patients with pT1 cN0 breast cancer treated by quadrantectomy do not benefit from RT. The 14.6% CCI of IBTR in our pT2 patients is an additional finding not presented in the trials and suggests that RT should be administered to elderly patients with pT2 disease.     

Radiotherapy, chemotherapy, and tamoxifen as adjuncts to surgery in early breast cancer: a summary of three randomized trials

The paper summarizes up-dated results of three randomized adjuvant trials from the Stockholm Breast Cancer Group. The objective of all studies included an evaluation of the role of megavoltage radiation in the primary management of patients with early breast cancer. The first trial was started in 1971 and included 960 pre- and postmenopausal patients with operable disease. The study compared adjuvant radiotherapy with surgery alone. All patients were treated with a modified radical mastectomy. There was a sustained improvement of the recurrence-free survival with radiotherapy (p less than 0.001). Among node positive cases radiation reduced the frequency of both loco-regional recurrence (p less than 0.001) and distant metastasis (p less than 0.01). This observation indicates that distant dissemination in subgroups of patients can originate from uncontrolled local deposits of tumor cells, for instance in the regional lymph nodes. No adverse effect from radiation on long-term survival was observed. The second study was started in 1976 and compared postmastectomy radiation with adjuvant chemotherapy in pre- and postmenopausal high-risk patients. At a mean follow-up of 6 1/2 years there was no significant difference in recurrence-free survival between the two treatments. However, postmenopausal patients fared better with radiotherapy (p less than 0.01). In this subgroup, radiation was more effective than adjuvant chemotherapy in reducing both distant metastases (p less than 0.01) and loco-regional recurrences (p less than 0.001). In the third trial--which only included postmenopausal patients--2 years of adjuvant tamoxifen was compared with no adjuvant endocrine treatment. The number of treatment failures was significantly reduced with tamoxifen (p less than 0.01) but there was no significant overall survival benefit. Subset analysis indicated that tamoxifen improved the recurrence-free survival among patients treated with adjuvant chemotherapy (p less than 0.01) but only to a level close to that achieved with radiotherapy alone. Addition of tamoxifen to radiotherapy failed to further increase the recurrence-free survival.     

Role of radiotherapy in small cell lung cancer

Traditionally, small cell lung cancer has been considered as a disease with early onset of distant metastases. Therefore, the role of locoregional therapy (radiotherapy or surgery) was thought to be very limited. This was supported by the first trials investigating the role of radiotherapy since there was no improvement of median survival. Recently, two meta-analyses changed this point of view: radiotherapy is essential to achieve long term survival. The possible biological explanation may be that uncontrolled distant metastases may cause the death of patients during the first months of their disease. The longer patients survive the more important local therapy becomes. Today, there is growing acceptance that adequate systemic and local therapy contributes to better treatment results of limited small cell lung cancer.     

Elderly breast cancer patients treated by conservative surgery alone plus adjuvant tamoxifen: fifteen-year results of a prospective study

BACKGROUND: In elderly patients with early breast cancer and a clinically clear axilla, axillary surgery, sentinel lymph node biopsy, and postoperative radiotherapy to the residual breast may not be necessary because of reduced life expectancy, effectiveness of hormone therapy in achieving long-term disease control, and generally favorable biologic behavior of breast cancer in elderly patients. METHODS: The authors followed 354 prospectively recruited women aged > or =70 years who had primary, operable breast cancer and no palpable axillary lymph nodes. All 354 women were treated with conservative surgery and adjuvant tamoxifen and without axillary dissection or postoperative radiotherapy. Women who had resection margins in tumor tissue were excluded. Endpoints were cumulative incidence of axillary disease, cumulative incidence of ipsilateral breast tumor recurrence (IBTR), and breast cancer mortality. RESULTS: After a median follow-up of 15 years (interquartile range, 14-17 years), the crude cumulative incidence was 4.2% (4% in pathologic T1 [pT1] tumors) for axillary disease, 8.3% (7.3% in pT1 tumors) for IBTR, and 17% for breast cancer mortality. Of the 268 patients who died during follow-up, 222 patients (83%) died from causes unrelated to breast cancer. CONCLUSIONS: Elderly patients with early breast cancer and no palpable axillary lymph nodes may be safely treated safety by conservative surgery without axillary dissection and without postoperative radiotherapy, provided that surgical margins are in tumor-free tissue and that hormone therapy is administered. Sentinel lymph node biopsy is also unnecessary because of the low cumulative incidence of axillary disease, and axillary surgery can be reserved for the small proportion of patients who later develop overt axillary disease.     

Human cancer natural history, radiation induced immunodepression and post-operative radiation therapy

For several types of cancers, post-operative radiation therapy is able to reduce the incidence of local recurrences, but has only a relatively small beneficial effect on total survival. Conversely to what has been claimed, this discrepancy is not due to a detrimental effect of radiotherapy. The data do not substantiate the hypothesis that irradiation through an impact on the immune system enhances growth of neoplastic foci outside of the irradiated volume. Several sets of data show that uncontrolled primary tumors or lymph node metastases can be important foci for distant spread. However the analysis of the data shows that post-operative radiotherapy can prevent metastatic spread only in a small subset of patients, those without distant metastases at the initial treatment and in whom local recurrences can be a nidus for distant dissemination before being detected and treated. The results of the clinical trials carried out on patients with breast cancers show that this situation is frequently observed in patients with tumors located in the inner quadrants of the breast who are those in whom the involvement of the internal mammary chain is relatively frequent.     

Adjuvant treatment of non-small-cell lung cancer: how do we improve the cure rates further?

Surgery remains the initial treatment for patients with early-stage non-small-cell lung cancer (NSCLC). Additional therapy is necessary because of high rates of distant and local disease recurrence after surgical resection. Early trials of adjuvant chemotherapy and postoperative radiation were often plagued by small patient sample size, inadequate surgical staging, and ineffective or antiquated treatment. A 1995 meta-analysis found a nonsignificant reduction in risk of death for postoperative cisplatin-based chemotherapy. Since then, a new generation of randomized phase III trials have been conducted, some of which have reported a benefit for chemotherapy in the adjuvant setting. The role of postoperative radiation therapy remains to be defined. It may not be beneficial in early-stage NSCLC but still may have utility in stage IIIA disease. Improvement in survival outcomes from adjuvant treatment are likely to result from the evaluation of novel agents, identification of tumor markers predictive of disease relapse, and definition of factors that determine sensitivity to therapeutic agents. Some of the molecularly targeted agents such as the angiogenesis and epidermal growth factor receptor inhibitors are being incorporated into clinical trials. Preliminary results with gene-expression profiles and lung cancer proteomics have been promising. These techniques may be used to create prediction models to identify patients at risk for disease relapse. Molecular markers such as ERCC1 may determine response to treatment. All of these innovations will hopefully increase cure rates for lung cancer patients by maximizing the efficacy of adjuvant therapy.     

Radiation therapy plus tamoxifen versus tamoxifen alone after breast-conserving surgery in postmenopausal women with stage I breast cancer: a decision analysis.

PURPOSE: To compare outcomes for hypothetical cohorts of postmenopausal patients with estrogen receptor-positive tumors that are < or = 2 cm in size, with pathologically uninvolved axillary nodes, treated with radiation therapy plus tamoxifen versus tamoxifen alone after breast-conserving surgery. METHODS: A Markov model was used to simulate patients' clinical course and estimate overall survival, recurrence-free survival, time with an intact breast, and death from breast cancer. Probabilities were derived from randomized trials and retrospective studies. Analyses were performed separately by age of diagnosis in 5-year increments from 50 to 80 years. Sensitivity analyses tested the stability of radiation benefit. RESULTS: The modeled recurrence-free survival benefit of giving radiation therapy was 3.35 years for women who were 50 years of age at diagnosis, versus 0.61 years for women who were 80 years of age. In the 50-year-old cohort, radiation therapy resulted in additional 0.60 years survival, compared with 0.04 years among 80-year-olds. A 50-year-old woman who received radiation therapy plus tamoxifen was less likely to die from breast cancer than if she received tamoxifen alone (2.43% v 5.29%; relative-risk reduction, 54%). An 80-year-old woman had a 1.17% chance of dying from breast cancer if she received radiation therapy plus tamoxifen, versus 2.02% with tamoxifen alone (relative-risk reduction, 42%). Sensitivity analyses showed that the magnitude of benefit was strongly influenced by including unequal rates of developing distant disease after breast recurrence between the treatment arms and varying rates of local recurrence. CONCLUSION: The absolute and relative benefits of radiation therapy and individual patient preferences for different health states should be considered when selecting treatment.