HeLa Cell Line in Wired

Wired has a nice little "gee whiz" article on the history of the HeLa cell line this month.

Link: http://www.wired.com/magazine/2010/01/st_henrietta/

Post Op prostate bed contouring atlas

This weeks red journal - A consensus atlas is designed for the RTOG in postop prostate. For the atlas follow this link:http://goo.gl/et6F

For the Article:

Development of RTOG Consensus Guidelines for the Definition of the Clinical Target Volume for Postoperative Conformal Radiation Therapy for Prostate Cancer: "Purpose: To define a prostate fossa clinical target volume (PF-CTV) for Radiation Therapy Oncology Group (RTOG) trials using postoperative radiotherapy for prostate cancer.Methods and Materials: An RTOG-sponsored meeting was held to define an appropriate PF-CTV after radical prostatectomy. Data were presented describing radiographic failure patterns after surgery. Target volumes used in previous trials were reviewed. Using contours independently submitted by 13 radiation oncologists, a statistical imputation method derived a preliminary “consensus” PF-CTV.Results: Starting from the model-derived CTV, consensus was reached for a CT image–based PF-CTV. The PF-CTV should extend superiorly from the level of the caudal vas deferens remnant to >8–12 mm inferior to vesicourethral anastomosis (VUA). Below the superior border of the pubic symphysis, the anterior border extends to the posterior aspect of the pubis and posteriorly to the rectum, where it may be concave at the level of the VUA. At this level, the lateral border extends to the levator ani. Above the pubic symphysis, the anterior border should encompass the posterior 1–2 cm of the bladder wall; posteriorly, it is bounded by the mesorectal fascia. At this level, the lateral border is the sacrorectogenitopubic fascia. Seminal vesicle remnants, if present, should be included in the CTV if there is pathologic evidence of their involvement.Conclusions: Consensus on postoperative PF-CTV for RT after prostatectomy was reached and is available as a CT image atlas on the RTOG website. This will allow uniformity in defining PF-CTV for clinical trials that include postprostatectomy RT."

Association of the Recurrence Score (Oncotype DX) with Local Recurrence

Online in the JCO:

The recurrence score (oncotype DX) has been an extremely valuable tool in decision making for the delivery of systemic therapy in node negative, ER+ breast cancer. The primary analyses published to date describe it's association with distant failure, survival and the relative benefit of cytotoxic chemotherapy. This article describes the association of this score with loco-regional recurrence, of upmost interest to radiation oncologists as we move to an era of personalized medicine. Perhaps not surprisingly, an association is indeed found. Of course whether radiation should be intensified somehow in the higher risk patients, or de-intensified in the lower risk patients is something that this report cannot address, but does open up the door to some potentially quite interesting clinical questions to test prospectively....

Link

Radiotherapy plus cetuximab for locoregionally advanced head and neck cancer: 5-year survival data from a phase 3 randomised trial, and relation between cetuximab-induced rash and survival

The "Bonner" trial reports five year data in this months Lancet Oncology. The initial survival benefit is continued out to longer follow up than the prior NEJM article. A subgroup analysis also demonstrates that in those recieving cetuximab, the development of a more severe acneiform rash was associated with an improved survival. This finding is similar to prior reports in colon cancer. What is causing this is unknown, but it may be a surrogate for reaching systemic drug levels...

Link -

[Articles] Radiotherapy plus cetuximab for locoregionally advanced head and neck cancer: 5-year survival data from a phase 3 randomised trial, and relation between cetuximab-induced rash and survival: "Previous results from our phase 3 randomised trial showed that adding cetuximab to primary radiotherapy increased overall survival in patients with locoregionally advanced squamous-cell carcinoma of the head and neck (LASCCHN) at 3 years. Here we report the 5-year survival data, and investigate the relation between cetuximab-induced rash and survival."

Phase I Study of Accelerated Conformal Radiotherapy for Stage I NSCLC

This weeks JCO:

The results of the CALGB 39904 trial are published after multiple abstract presentations. This was looking at an alternative to SBRT in the treatment of early stage NSCLC, increasing the intensity of treatment, while keeping the nominal dose stable at 70Gy. The results are encouraging, however, SBRT has probably already lapped this style of RT for this patient population.

Link and Abstract

Phase I Study of Accelerated Conformal Radiotherapy for Stage I Non-Small-Cell Lung Cancer in Patients With Pulmonary Dysfunction: CALGB 39904 [Thoracic Oncology]: "Purpose

The optimal treatment for medically inoperable stage I non–small-cell lung cancer (NSCLC) has not been defined.

Patients and Methods

Cancer and Leukemia Group B trial 39904 prospectively assessed accelerated, once-daily, three-dimensional radiotherapy for early-stage NSCLC. The primary objectives were to define the maximally accelerated course of conformal radiotherapy and to describe the short-term and long-term toxicity of therapy. Entry was limited to patients with clinical stage T1N0 or T2N0 NSCLC (< 4 cm) and pulmonary dysfunction. The nominal total radiotherapy dose remained at 70 Gy, while the number of daily fractions in each successive cohort was reduced.

Results

Thirty-nine eligible patients were accrued (eight patients each on cohorts 1 to 4 and seven patients on cohort 5) between January 2001 and July 2005. One grade 3 nonhematologic toxicity was observed in both cohort 3 (dyspnea) and cohort 4 (pain). The major response rate was 77%. After a median follow-up time of 53 months, the actuarial median survival time of all eligible patients was 38.5 months. Local relapse was observed in three patients.

Conclusion

Accelerated conformal radiotherapy was well tolerated in a high-risk population with clinical stage I NSCLC. Outcomes are comparable to prospective reports of alternative therapies, including stereotactic body radiation therapy and limited resection, with less apparent severe toxicity. Further investigation of this approach is warranted.

"

Radiation Pneumonitis after Radiotherapy for Breast Cancer

the NEJM of the week has a good example of radiation pneumonitis

Link-

Radiation Pneumonitis after Radiotherapy for Breast Cancer:

Adjuvant Chemotherapy for NSCLC, updates on two influential trials

JCO this week: Two of the more influencial trials on adjuvant chemotherapy for resected NSCLC are updated, the JBR-10 and the IALT studies. The JBR-10 study continues to show a survival benefit out to almost 10 years, though the stage IBs seemed not to benefit. The IALT study continued to demonstrate a DFS benefit, but the OS figures had slipped to non-significance.

Links and abstracts:

Randomized Phase III Trial of Vinorelbine Plus Cisplatin Compared With Observation in Completely Resected Stage IB and II Non-Small-Cell Lung Cancer: Updated Survival Analysis of JBR-10 [Thoracic Oncology]: "Purpose

Adjuvant cisplatin-based chemotherapy (ACT) is now an accepted standard for completely resected stage II and III A non–small-cell lung cancer (NSCLC). Long-term follow-up is important to document persistent benefit and late toxicity. We report here updated overall survival (OS) and disease-specific survival (DSS) data.

Patients and Methods

Patients with completely resected stage IB (T2N0, n = 219) or II (T1-2N1, n = 263) NSCLC were randomly assigned to receive 4 cycles of vinorelbine/cisplatin or observation. All efficacy analyses were performed on an intention-to-treat basis.

Results

Median follow-up was 9.3 years (range, 5.8 to 13.8; 33 lost to follow-up); there were 271 deaths in 482 randomly assigned patients. ACT continues to show a benefit (hazard ratio [HR], 0.78; 95% CI, 0.61 to 0.99; P = .04). There was a trend for interaction with disease stage (P = .09; HR for stage II, 0.68; 95% CI, 0.5 to 0.92; P = .01; stage IB, HR, 1.03; 95% CI, 0.7 to 1.52; P = .87). ACT resulted in significantly prolonged DSS (HR, 0.73; 95% CI, 0.55 to 0.97; P = .03). Observation was associated with significantly higher risk of death from lung cancer (P = .02), with no difference in rates of death from other causes or second primary malignancies between the arms.

Conclusion

Prolonged follow-up of patients from the JBR.10 trial continues to show a benefit in survival for adjuvant chemotherapy. This benefit appears to be confined to N1 patients. There was no increase in death from other causes in the chemotherapy arm."

Long-Term Results of the International Adjuvant Lung Cancer Trial Evaluating Adjuvant Cisplatin-Based Chemotherapy in Resected Lung Cancer [Thoracic Oncology]

Purpose

Based on 5-year or shorter-term follow-up data in recent randomized trials, adjuvant cisplatin-based chemotherapy is now generally recommended after complete surgical resection for patients with non–small-cell lung cancer (NSCLC). We evaluated the results of the International Adjuvant Lung Cancer Trial study with three additional years of follow-up.

Patients and Methods

Patients with completely resected NSCLC were randomly assigned to three or four cycles of cisplatin-based chemotherapy or to observation. Cox models were used to evaluate treatment effect according to follow-up duration.

Results

The trial included 1,867 patients with a median follow-up of 7.5 years. Results showed a beneficial effect of adjuvant chemotherapy on overall survival (hazard ratio [HR], 0.91; 95% CI, 0.81 to 1.02; P = .10) and on disease-free survival (HR, 0.88; 95% CI, 0.78 to 0.98; P = .02). However, there was a significant difference between the results of overall survival before and after 5 years of follow-up (HR, 0.86; 95% CI, 0.76 to 0.97; P = .01 v HR, 1.45; 95% CI, 1.02 to 2.07; P = .04) with P = .006 for interaction. Similar results were observed for disease-free survival. The analysis of non-lung cancer deaths for the whole period showed an HR of 1.34 (95% CI, 0.99 to 1.81; P = .06).

Conclusion

These results confirm the significant efficacy of adjuvant chemotherapy at 5 years. The difference in results beyond 5 years of follow-up underscores the need for the long-term follow-up of other adjuvant lung cancer trials and for a better identification of patients deriving long-term benefit from adjuvant chemotherapy.

Results in stage I, II LPHD

A retrospective study from Dana-Farber reports on outcomes from LPHD (lymphocyte predominant Hodgkin's disease). They report excellent 10yr results with limited field RT. Chemotherapy alone resulted in poor PFS, however most were salvaged. Larger fields did not appear to improve results.

Link and Abstract:

Early-Stage, Lymphocyte-Predominant Hodgkin's Lymphoma: Patient Outcomes From a Large, Single-Institution Series With Long Follow-Up [Hematologic Malignancies]: "Purpose

The optimal treatment for early-stage, lymphocyte-predominant Hodgkin's lymphoma (LPHL) is not well defined. Treatment has become less aggressive over time in an attempt to reduce iatrogenic complications, such as cardiac mortality and second cancers, but long-term efficacy is unclear. We present the long-term outcome of patients treated at a single institution.

Patients and Methods

The study population includes 113 patients with stage I or II LPHL treated between 1970 and 2005. Pathologic diagnosis for all patients was confirmed using standard criteria. Ninety-three patients received radiation therapy (RT) alone, 13 received RT with chemotherapy, and seven received chemotherapy alone. Among patients treated with RT, 25 received limited-field, 35 received regional-field, and 46 received extended-field RT.

Results

Median follow-up was 136 months. Ten-year progression-free survival (PFS) rates were 85% (stage I) and 61% (stage II); overall survival (OS) rates were 94% and 97% for stages I and II, respectively. PFS and OS did not differ among patients who received limited-field, regional-field, or extended-field RT. In contrast, six of seven patients who received chemotherapy alone without RT developed early disease progression and required salvage treatment. Multivariable analysis adjusting for extent of RT, clinical stage, sex, and use of chemotherapy confirmed that the extent of RT was not significantly associated with PFS (P = .67) or OS (P = .99). The addition of chemotherapy to RT did not improve PFS or OS compared with RT alone.

Conclusion

RT alone leads to sustained disease control and high long-term survival rates in patients with early-stage LPHL. This study supports the use of limited-field RT alone to treat this disease."

Active surveillance for Low risk Prostate Cancer

JCO this week:

A single arm study from Canada suggests that active surveillance is a reasonable option in low risk ACP. Though 50% of those that did undergo radical treatment ended up having PSA failure, it was only 13% of the overall cohort. That said the follow up remains a little short at just under seven years; I would like to see 10-15 year data reported due to the fact that often prostate cancer death occurs much later than detection or biochemical failure.

Link and Abstract

Clinical Results of Long-Term Follow-Up of a Large, Active Surveillance Cohort With Localized Prostate Cancer [Genitourinary Cancer]: "Purpose

We assessed the outcome of a watchful-waiting protocol with selective delayed intervention by using clinical prostate-specific antigen (PSA), or histologic progression as treatment indications for clinically localized prostate cancer.

Patients and Methods

This was a prospective, single-arm, cohort study. Patients were managed with an initial expectant approach. Definitive intervention was offered to those patients with a PSA doubling time of less than 3 years, Gleason score progression (to 4 + 3 or greater), or unequivocal clinical progression. Survival analysis and Cox proportional hazard model were applied to the data.

Results

A total of 450 patients have been observed with active surveillance. Median follow-up was 6.8 years (range, 1 to 13 years). Overall survival was 78.6%. The 10-year prostate cancer actuarial survival was 97.2%. Overall, 30% of patients have been reclassified as higher risk and have been offered definitive therapy. Of 117 patients treated radically, the PSA failure rate was 50%, which was 13% of the total cohort. PSA doubling time of 3 years or less was associated with an 8.5-times higher risk of biochemical failure after definitive treatment compared with a doubling time of more than 3 years (P < .0001). The hazard ratio for nonprostate cancer to prostate cancer mortality was 18.6 at 10 years.

Conclusion

We observed a low rate of prostate cancer mortality. Among the patients who were reclassified as higher risk and who were treated, PSA failure was relatively common. Other-cause mortality accounted for almost all of the deaths. Additional studies are warranted to improve the identification of patients who harbor more aggressive disease despite favorable clinical parameters at diagnosis."

Induction Cetuximab, Paclitaxel and Carboplatin in H&N cancers

JCO this week: MD Anderson reports the results of a Phase II combining cetuximab, paclitaxel and carboplatin before definitive surgery, radiation or chemoradiation. Interesting results, but obviously the overall question of whether induction is the best approach remains up in the air. Abstract and link:

Induction Chemotherapy and Cetuximab for Locally Advanced Squamous Cell Carcinoma of the Head and Neck: Results From a Phase II Prospective Trial [Head and Neck Cancer]: "Purpose

To determine the potential efficacy of combining cetuximab with chemotherapy in patients with advanced nodal disease, we conducted a phase II trial with induction chemotherapy (ICT) consisting of six weekly cycles of paclitaxel 135 mg/m² and carboplatin (area under the curve = 2) with cetuximab 400 mg/m² in week 1 and then 250 mg/m² (PCC).

Patients and Methods

Forty-seven previously untreated patients (41 with oropharynx primaries; 33 men, 14 women; median age, 53 years; performance status of 0 or 1) with squamous cell carcinoma of the head and neck (SCCHN; T1-4, N2b/c/3) were treated and evaluated for clinical and radiographic response. After ICT, patients underwent risk-based local therapy, which consisted of either radiation, concomitant chemoradiotherapy, or surgery, based on tumor stage and site at diagnosis.

Results

After induction PCC, nine patients (19%) achieved a complete response, and 36 patients (77%) achieved a partial response. The most common grade 3 or 4 toxicity was skin rash (45%), followed by neutropenia (21%) without fever. At a median follow-up time of 33 months, locoregional or systemic disease progression was observed in six patients. The 3-year progression-free survival (PFS) and overall survival (OS) rates were 87% (95% CI, 78% to 97%) and 91% (95% CI, 84% to 99%), respectively. Human papillomavirus (HPV) 16, found in 12 (46%) of 26 biopsies, was associated with improved PFS (P = .012) and OS (P = .046).

Conclusion

ICT with weekly PCC followed by risk-based local therapy seems to be feasible, effective, and well tolerated. PFS is promising, and this sequential treatment strategy should be further investigated. Patients with HPV-positive tumors have an excellent prognosis."

soy and breast cancer survival.

For those that Had Tofurky for Thanksgiving Dinner like me:

from JAMA - abstract and link

Soy Food Intake and Breast Cancer Survival [Original Contribution]: "

Context Soy foods are rich in isoflavones, a major group of phytoestrogens that have been hypothesized to reduce the risk of breast cancer. However, the estrogen-like effect of isoflavones and the potential interaction between isoflavones and tamoxifen have led to concern about soy food consumption among breast cancer patients.

Objective To evaluate the association of soy food intake after diagnosis of breast cancer with total mortality and cancer recurrence.

Design, Setting, and Participants The Shanghai Breast Cancer Survival Study, a large, population-based cohort study of 5042 female breast cancer survivors in China. Women aged 20 to 75 years with diagnoses between March 2002 and April 2006 were recruited and followed up through June 2009. Information on cancer diagnosis and treatment, lifestyle exposures after cancer diagnosis, and disease progression was collected at approximately 6 months after cancer diagnosis and was reassessed at 3 follow-up interviews conducted at 18, 36, and 60 months after diagnosis. Annual record linkage with the Shanghai Vital Statistics Registry database was carried out to obtain survival information for participants who were lost to follow-up. Medical charts were reviewed to verify disease and treatment information.

Main Outcome Measures Total mortality and breast cancer recurrence or breast cancer–related deaths. Cox regression analysis was carried out with adjustment for known clinical predictors and other lifestyle factors. Soy food intake was treated as a time-dependent variable.

Results During the median follow-up of 3.9 years (range, 0.5-6.2 years), 444 deaths and 534 recurrences or breast cancer–related deaths were documented in 5033 surgically treated breast cancer patients. Soy food intake, as measured by either soy protein or soy isoflavone intake, was inversely associated with mortality and recurrence. The hazard ratio associated with the highest quartile of soy protein intake was 0.71 (95% confidence interval [CI], 0.54-0.92) for total mortality and 0.68 (95% CI, 0.54-0.87) for recurrence compared with the lowest quartile of intake. The multivariate-adjusted 4-year mortality rates were 10.3% and 7.4%, and the 4-year recurrence rates were 11.2% and 8.0%, respectively, for women in the lowest and highest quartiles of soy protein intake. The inverse association was evident among women with either estrogen receptor–positive or –negative breast cancer and was present in both users and nonusers of tamoxifen.

Conclusion Among women with breast cancer, soy food consumption was significantly associated with decreased risk of death and recurrence.

"

RT first or Chemo first in Anaplastic Glioma

In the JCO this week:

Randomized data in different sequences of RT and Chemo in anaplastic Chemo. The bottom line from my take is that there is no significant difference in outcome, but toxicity is worse with chemo first. It is puzzling then that the conclusions of the paper state "These data may allow recommending chemotherapy as first-line treatment of patients with anaplastic gliomas, including patients with AA." That seems a bit at odds with the data presented - i.e. when you have two arms with equivalent therapeutic outcome, toxicity should drive the treatment decision, clearly favoring RT. It was also designed as a superiority trial for chemotherapy first, not a non-inferiority trial, so really it surely doesn't prove that chemo is as effective as RT either.

Link and astract:

NOA-04 Randomized Phase III Trial of Sequential Radiochemotherapy of Anaplastic Glioma With Procarbazine, Lomustine, and Vincristine or Temozolomide [Neurooncology]: "Purpose

The standard of care for anaplastic gliomas is surgery followed by radiotherapy. The NOA-04 phase III trial compared efficacy and safety of radiotherapy followed by chemotherapy at progression with the reverse sequence in patients with newly diagnosed anaplastic gliomas.

Patients and Methods

Patients (N = 318) were randomly assigned 2:1:1 (A:B1:B2) to receive conventional radiotherapy (arm A); procarbazine, lomustine (CCNU), and vincristine (PCV; arm B1); or temozolomide (arm B2) at diagnosis. At occurrence of unacceptable toxicity or disease progression, patients in arm A were treated with PCV or temozolomide (1:1 random assignment), whereas patients in arms B1 or B2 received radiotherapy. The primary end point was time to treatment failure (TTF), defined as progression after radiotherapy and one chemotherapy in either sequence.

Results

Patient characteristics in the intention-to-treat population (n = 274) were balanced between arms. All histologic diagnoses were centrally confirmed. Median TTF (hazard ratio [HR] = 1.2; 95% CI, 0.8 to 1.8), progression-free survival (PFS; HR = 1.0; 95% CI, 0.7 to 1.3, and overall survival (HR = 1.2; 95% CI, 0.8 to 1.9) were similar for arms A and B1/B2. Extent of resection was an important prognosticator. Anaplastic oligodendrogliomas and oligoastrocytomas share the same, better prognosis than anaplastic astrocytomas. Hypermethylation of the O⁶-methylguanine DNA-methyltransferase (MGMT) promoter (HR = 0.59; 95% CI, 0.36 to 1.0), mutations of the isocitrate dehydrogenase (IDH1) gene (HR = 0.48; 95% CI, 0.29 to 0.77), and oligodendroglial histology (HR = 0.33; 95% CI, 0.2 to 0.55) reduced the risk of progression. Hypermethylation of the MGMT promoter was associated with prolonged PFS in the chemotherapy and radiotherapy arm.

Conclusion

Initial radiotherapy or chemotherapy achieved comparable results in patients with anaplastic gliomas. IDH1 mutations are a novel positive prognostic factor in anaplastic gliomas, with a favorable impact stronger than that of 1p/19q codeletion or MGMT promoter methylation."

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.

"

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.

"

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."

Preoperative Multimodality Therapy Improves Disease-Free Survival in Patients With Carcinoma of the Rectum: NSABP R-03 [Gastrointestinal Cancer]

JCO this week: the NSABP R03 is published. A preop vs postop CTRT trial for rectal cancer, similar to the practice defining German trial. Unfortunately underpowered, it nonetheless demonstrates a DFS benefit. How to interpret this benefit in the light of no difference in LC is slightly more problematic, especially comparing to the larger German trial.

Link and Abstract:

Preoperative Multimodality Therapy Improves Disease-Free Survival in Patients With Carcinoma of the Rectum: NSABP R-03 [Gastrointestinal Cancer]: "Purpose

Although chemoradiotherapy plus resection is considered standard treatment for operable rectal carcinoma, the optimal time to administer this therapy is not clear. The NSABP R-03 (National Surgical Adjuvant Breast and Bowel Project R-03) trial compared neoadjuvant versus adjuvant chemoradiotherapy in the treatment of locally advanced rectal carcinoma.

Patients and Methods

Patients with clinical T3 or T4 or node-positive rectal cancer were randomly assigned to preoperative or postoperative chemoradiotherapy. Chemotherapy consisted of fluorouracil and leucovorin with 45 Gy in 25 fractions with a 5.40-Gy boost within the original margins of treatment. In the preoperative group, surgery was performed within 8 weeks after completion of radiotherapy. In the postoperative group, chemotherapy began after recovery from surgery but no later than 4 weeks after surgery. The primary end points were disease-free survival (DFS) and overall survival (OS).

Results

From August 1993 to June 1999, 267 patients were randomly assigned to NSABP R-03. The intended sample size was 900 patients. Excluding 11 ineligible and two eligible patients without follow-up data, the analysis used data on 123 patients randomly assigned to preoperative and 131 to postoperative chemoradiotherapy. Surviving patients were observed for a median of 8.4 years. The 5-year DFS for preoperative patients was 64.7% v 53.4% for postoperative patients (P = .011). The 5-year OS for preoperative patients was 74.5% v 65.6% for postoperative patients (P = .065). A complete pathologic response was achieved in 15% of preoperative patients. No preoperative patient with a complete pathologic response has had a recurrence.

Conclusion

Preoperative chemoradiotherapy, compared with postoperative chemoradiotherapy, significantly improved DFS and showed a trend toward improved OS.

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[Articles] Neurocognition in patients with brain metastases treated with radiosurgery or radiosurgery plus whole-brain irradiation: a randomised controlled trial

Presented at ASTRO last year as a plenary, the MDA randomized trial of SRS alone vs SRS + WBRT is published in Lancet Oncology. This is an interesting trial, as it had a neurocognitive primary endpoint, which is one of the larger concerns with WBRT. This trial certainly adds to the data on the neurocognitive effects of WBRT, however, one can't help but focus on the survival difference between the arms. I would venture that the data presented in the paper, especially the lack of any differences in neurologic deaths and the lack of any difference in the larger RTOG and Japanese trials, that this is not a treatment effect. Then the question remains, what did cause this, and could it have influenced the primary endpoint? Another point that I will add to this is the trial was stopped due to a 4 month evaluation of memory, as opposed to a later time point. I would suggest that this may be too early of a measurement time for the long term effects of WBRT.

Nonetheless, this trial does support the use of SRS alone in this population and the prospective nature of the neurocognitive evaluation is to be applauded.

Link:

[Articles] Neurocognition in patients with brain metastases treated with radiosurgery or radiosurgery plus whole-brain irradiation: a randomised controlled trial: "It is unclear whether the benefit of adding whole-brain radiation therapy (WBRT) to stereotactic radiosurgery (SRS) for the control of brain-tumours outweighs the potential neurocognitive risks. We proposed that the learning and memory functions of patients who undergo SRS plus WBRT are worse than those of patients who undergo SRS alone. We did a randomised controlled trial to test our prediction."