Preoperative Chemotherapy Versus Preoperative Chemoradiotherapy for Stage III (N2) Non–Small-Cell Lung Cancer

From the Red Journal: Shameless self and departmental promotion below

Link and Abstract

Preoperative Chemotherapy Versus Preoperative Chemoradiotherapy for Stage III (N2) Non–Small-Cell Lung Cancer: "Purpose: To compare preoperative chemotherapy (ChT) and preoperative chemoradiotherapy (ChT-RT) in operable Stage III non–small-cell lung cancer.Methods and Materials: This retrospective study analyzed all patients with pathologically confirmed Stage III (N2) non–small-cell lung cancer who initiated preoperative ChT or ChT-RT at Duke University between 1995 and 2006. Mediastinal pathologic complete response (pCR) rates were compared using a chi-square test. The actuarial overall survival, disease-free survival, and local control were estimated using the Kaplan-Meier method and compared using the log–rank test. Multivariate Cox regression analysis was also performed.Results: A total of 101 patients who initiated preoperative therapy with planned resection were identified. The median follow-up was 20 months for all patients and 38 months for survivors. The mediastinal lymph nodes were reassessed after preoperative therapy in 88 patients (87%). Within this group, a mediastinal pCR was achieved in 35% after preoperative ChT vs. 65% after preoperative ChT-RT (p = 0.01). Resection was performed in 69% after ChT and 84% after ChT-RT (p = 0.1). For all patients, the overall survival, disease-free survival, and local control rate at 3 years was 40%, 27%, and 66%, respectively. No statistically significant differences were found in the clinical endpoints between the ChT and ChT-RT subgroups. On multivariate analysis, a mediastinal pCR was associated with improved disease-free survival (p = 0.03) and local control (p = 0.03), but not overall survival (p = 0.86).Conclusion: Preoperative ChT-RT was associated with higher mediastinal pCR rates but not improved survival."

Roles of Radiation Dose and Chemotherapy in the Etiology of Stomach Cancer as a Second Malignancy

From the Red Journal: An interesting report of secondary cancers due to RT... this time stomach adenocarcinomas, not something that I usually think of.

Link and Abstract

Roles of Radiation Dose and Chemotherapy in the Etiology of Stomach Cancer as a Second Malignancy: "Purpose: To evaluate the roles of radiation dose, chemotherapy, and other factors in the etiology of stomach cancer in long-term survivors of testicular cancer or Hodgkin lymphoma.Methods and Materials: We conducted a cohort study in 5,142 survivors of testicular cancer or Hodgkin lymphoma treated in the Netherlands between 1965 and 1995. In a nested case–control study, detailed information on treatment, smoking, gastrointestinal diseases, and family history was collected for 42 patients with stomach cancer and 126 matched controls. For each subject, the mean radiation dose to the stomach was estimated. Relative risks (RRs) of stomach cancer and the radiation-related excess relative risk (ERR) per gray were calculated by conditional logistic regression analysis.Results: The risk of stomach cancer was 3.4-fold increased compared with the general population. The risk increased with increasing mean stomach dose (p for trend, <0.001), at an ERR of 0.84 per Gy (95% confidence interval [CI], 0.12–15.6). Mean stomach doses of more than 20 Gy were associated with a RR of 9.9 (95% CI, 3.2–31.2) compared with doses below 11 Gy. The risk was 1.8-fold (95% CI, 0.8–4.4) increased after chemotherapy and 5.4-fold (95% CI, 1.2–23.9) increased after high doses of procarbazine (≥13,000 mg) vs. <10,000 mg. The RR of smoking more than 10 cigarettes per day vs. no smoking was 1.6 (95% CI, 0.6–4.2).Conclusions: Stomach cancer risk is strongly radiation dose dependent. The role of chemotherapy, particularly of procarbazine and related agents, needs further study, because of the relatively small numbers of chemotherapy-treated subjects."

Toxicity of Three-Dimensional Conformal Radiotherapy for Accelerated Partial Breast Irradiation

From the Red Journal: EBRT based PBRT may not be the best solution...

Link and Abstract

Toxicity of Three-Dimensional Conformal Radiotherapy for Accelerated Partial Breast Irradiation: "Purpose: To assess the incidence and severity of late normal tissue toxicity using three-dimensional conformal radiotherapy to deliver accelerated partial breast irradiation.Methods and Materials: A total of 60 patients were treated with three-dimensional conformal radiotherapy for accelerated partial breast irradiation. Treatment planning and delivery were in strict accordance with the technique and specified dose–volume constraints of the National Surgical Adjuvant Breast and Bowel Project B-39/Radiation Therapy Oncology Group 0413 protocol. Late toxicity was evaluated according to the Radiation Therapy Oncology Group grading schema. The cosmetic outcome was scored using the Harvard criteria. Univariate logistic regression analysis was performed to evaluate the correlation of dosimetric variables with outcome.Results: At a median follow-up of 15 months, moderate-to-severe late toxicity developed in 10% of patients. The most pronounced late toxicity was subcutaneous fibrosis: 25% Grade 2-4 and 8.3% Grade 3-4. The modified planning tumor volume/whole breast volume ratio, ratio of the volume of breast tissue receiving 5%, 20%, 50%, and 80% of the prescription dose to the whole breast volume, and maximal dose within the breast correlated with the development of fibrosis (p = .10, p = .03, p = .04, p = .06, p = .09, and p = .046, respectively). The overall cosmetic outcome was good to excellent in 81.7%, fair in 11.7%, and poor in 6.7%. The presence of subcutaneous fibrosis, modified planning tumor volume/whole breast volume ratio, ratio of the volume of breast tissue receiving 5% and 20% of the prescription dose to the whole breast volume, and pathologic specimen volume correlated with the risk of a fair/poor cosmetic outcome (p < .001, p = .02, p = .05, p = .04, p = .01, respectively).Conclusion: The three-dimensional conformal radiotherapy technique for accelerated partial breast irradiation as specified in the National Surgical Adjuvant Breast and Bowel Project B-39/Radiation Therapy Oncology Group 0413 protocol resulted in a remarkably high rate of moderate-to-severe late normal tissue effects, despite the relatively brief follow-up period. The toxic events correlated clearly with several dose–volume parameters."

Randomized Comparison of the Stanford V Regimen and ABVD in the Treatment of Advanced Hodgkin's Lymphoma: United Kingdom National Cancer Research Institute Lymphoma Group Study ISRCTN 64141244 [Hematologic Malignancies]

This week's JCO:

For Advanced HD, a randomized trial from the UK reports on the relative efficacy of Stanford V vs ABVD. The short answer - both are ok, just different toxicities. Most of the patients received RT in both arms, however usage was higher with Stanford V. This is due to the fact that mid trial, patients in CR after ABVD did not recieve RT, whereas RT is an integral part of the Stanford V regimen.

Link and Abstract:

Randomized Comparison of the Stanford V Regimen and ABVD in the Treatment of Advanced Hodgkin's Lymphoma: United Kingdom National Cancer Research Institute Lymphoma Group Study ISRCTN 64141244 [Hematologic Malignancies]: "Purpose

This multicenter, prospective, randomized controlled trial compared the efficacy and toxicity of two chemotherapy regimens in advanced Hodgkin's lymphoma (HL): the weekly alternating Stanford V and the standard, twice-weekly regimen of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD).

Patients and Methods

Patients had stage IIB, III, or IV disease or had stages I to IIA disease with bulky disease or other adverse features. Radiotherapy was administered in both arms to sites of previous bulk (> 5 cm) and to splenic deposits, although this was omitted in the latter part of the trial for patients achieving complete remission (CR) in the ABVD arm. A total of 520 patients were randomly assigned and were assessed for the primary outcome measure of progression-free survival (PFS). Five hundred patients received protocol treatment, and radiotherapy was administered to 73% in the Stanford V arm and to 53% in the ABVD arm.

Results

The overall response rates after completion of all treatment were 91% for Stanford V and 92% for ABVD. During a median follow-up of 4.3 years, there was no evidence of a difference in projected 5-year PFS and overall survival (OS) rates (76% and 90%, respectively, for ABVD; 74% and 92%, respectively, for Stanford V). More pulmonary toxicity was reported for ABVD, whereas other toxicities were more frequent with Stanford V.

Conclusion

In a large, randomized trial, the efficacies of Stanford V and ABVD were comparable when given in combination with appropriate radiotherapy.

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Local Excision Alone Without Irradiation for Ductal Carcinoma In Situ of the Breast: A Trial of the Eastern Cooperative Oncology Group [Breast Cancer]

This weeks JCO:

A very interesting article on lumpectomy alone in selected DCIS patients is reported from ECOG and the NCTG. This was a phase II trial of lumpectomy alone small (<2.5cm)>3mm). The five year results meet their goals in the low-intermediate grade group with 6.1% ipsilateral events, however was unacceptably high in the high grade group. These two cohorts were planned from the start to be analyzed separately.

The only comment that I would have is that I will like to see the 10 year data when it is available, as the failure curves in the manuscript look like they are begining to jump after the currently reported endpoint.

Of course, the real test of lumpectomy alone in selected DCIS will be the randomized RTOG trial 98-04 which will be maturing with the next few years.

Link and Abstract:

Local Excision Alone Without Irradiation for Ductal Carcinoma In Situ of the Breast: A Trial of the Eastern Cooperative Oncology Group [Breast Cancer]: "Purpose

To determine the risk of ipsilateral breast events in patients with ductal carcinoma in situ (DCIS) treated with local excision without irradiation.

Patients and Methods

Patients with either low- or intermediate-grade DCIS measuring 2.5 cm or smaller, or high-grade DCIS measuring 1 cm or smaller who had microscopic margin widths of 3 mm or wider and no residual calcifications on postoperative mammograms were eligible for a prospective trial conducted from 1997 to 2002 by the Eastern Cooperative Oncology Group and North Central Cancer Treatment Group. Patients entered in 2000 and later could take tamoxifen if they wished. Median age at last surgery for the entire population was 60 years (range, 28 to 88 years), and median tumor sizes in the two strata were 6 mm and 5 mm, respectively.

Results

With a median follow-up of 6.2 years, the 5-year rate of ipsilateral breast events in the 565 eligible patients in the low/intermediate grade stratum was 6.1% (95% CI, 4.1% to 8.2%). With a median follow-up of 6.7 years, this incidence for the 105 eligible patients in the high-grade stratum was 15.3% (95% CI, 8.2% to 22.5%).

Conclusion

Rigorously evaluated and selected patients with low- to intermediate-grade DCIS with margins 3 mm or wider had an acceptably low rate of ipsilateral breast events at 5 years after excision without irradiation. Patients with high-grade lesions had a much higher rate, suggesting that excision alone is inadequate treatment. Further follow-up is necessary to document long-term results.

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Relationship Between Potentially Modifiable Lifestyle Factors and Risk of Second Primary Contralateral Breast Cancer Among Women Diagnosed With Estrogen Receptor-Positive Invasive Breast Cancer [Breast Cancer]

From this weeks JCO:

Nothing surprising in this retrospective study, but it lends more weight to the idea of promoting healthy lifestyles in cancer survivors. This is definitely useful to answer a question that we often hear from our patients :"what can I do to prevent another cancer?"

Link and Abstract

Relationship Between Potentially Modifiable Lifestyle Factors and Risk of Second Primary Contralateral Breast Cancer Among Women Diagnosed With Estrogen Receptor-Positive Invasive Breast Cancer [Breast Cancer]: "Purpose

An outcome of considerable concern among breast cancer survivors is the development of second primary breast cancer. However, evidence regarding how potentially modifiable lifestyle factors modulate second breast cancer risk is limited. We evaluated the relationships between obesity, alcohol consumption, and smoking on risk of second primary invasive contralateral breast cancer among breast cancer survivors.

Methods

Utilizing a population-based nested case-control study design, we enrolled 365 patients diagnosed with an estrogen receptor–positive (ER+) first primary invasive breast cancer and a second primary contralateral invasive breast cancer, and 726 matched controls diagnosed with only an ER+ first primary invasive breast cancer. Obesity, alcohol use, and smoking data were ascertained from medical record reviews and participant interviews. Using conditional logistic regression we evaluated associations between these three exposures and second primary contralateral breast cancer risk.

Results

Obesity, consumption of ≥ 7 alcoholic beverages per week, and current smoking were all positively related to risk of contralateral breast cancer (odds ratio [OR], 1.4; 95% CI, 1.0 to 2.1; OR, 1.9; 95% CI, 1.1 to 3.2; and OR, 2.2; 95% CI, 1.2 to 4.0, respectively). Compared with women who consumed fewer than seven alcoholic beverages per week and were never or former smokers, women who consumed ≥ 7 drinks per week and were current smokers had a 7.2-fold (95% CI, 1.9 to 26.5) elevated risk of contralateral breast cancer.

Conclusion

Our population-based study adds to the limited available literature and suggests that obesity, smoking, and alcohol consumption influence contralateral breast cancer risk, affording breast cancer survivors three means of potentially reducing this risk."