JCO: Prognosis with Radiation Associated Sarcomas

From the JCO:

An interesting series of radiation associated soft tissue sarcomas from MSKCC, which attempts to determine if there are differences in the prognosis with a matched cohort of sporadic STS. The DSS was indeed different with an HR of 1.7(p=0.007) on MVA, however, it is significant to note that the radiation associated tumors were not given RT as often (~50% less). How this difference in treatment may have affected outcomes is uncertain, however this could certainly contribute to the difference outcomes. Regardless, it is a worthwhile subject of study, and the mansucript is worth review for the practicing radiation oncologist.

Link and Abstract:

Do Radiation-Associated Soft Tissue Sarcomas Have the Same Prognosis As Sporadic Soft Tissue Sarcomas? [Sarcomas]: "Purpose

To determine the prognostic significance of histologic type in radiation-associated soft tissue sarcomas (RASs) and determine whether RASs are associated with an inferior prognosis compared with sporadic soft tissue sarcomas (STSs).

Patients and Methods

One hundred thirty primary RASs were identified from 7,649 STS patients from 1982 to 2007. Multivariate analysis of clinicopathologic factors for disease-specific survival (DSS) was performed for RASs, and a multivariate analysis of radiation exposure was also performed for RASs and sporadic sarcomas. A matched-cohort analysis was performed for radiation-associated and sporadic malignant fibrous histiocytoma (MFH).

Results

Most RASs were high grade (83%), deep (87%), and truncal (61.5%). The median interval between radiation therapy and RAS development was 10 years (range, 1.3 to 74 years), which varied significantly by histologic type (P = .003). The 5-year DSS was 58%, and independent predictors were size > 5 cm, margin positivity, and histologic type. Multivariate analysis of histologic types of primary, high-grade radiation-associated and sporadic STSs showed that RAS was associated with a worse DSS (hazard ratio, 1.7; range, 1.1 to 2.4; P = .007). For pleomorphic MFH—the most common RAS type—the 5-year DSS was 44% versus 66% in a matched cohort of sporadic MFH patients (P = .07). DSS was significantly worse in primary RAS malignant peripheral nerve sheath tumors (MPNSTs) compared with unmatched sporadic MPNSTs (P = .001).

Conclusion

Histologic type, margin status, and tumor size are the most important independent predictors of DSS in patients with RASs. DSS in patients with primary RAS is significantly worse compared with sporadic STS independent of sarcoma histologic type."

Predictive Nomogram for Brain Metastases in Metastatic Breast Cancer

In the JCO:

Investigators from MDACC have developed a nomogram which calculates the risk of brain metastases in patients with metastatic breast cancer, validated in the current manuscript with a cohort from Canada. Risk factors are what one might expect (high grade, low age, multiple sites of metastasis, HER2 positivity). Of course this then begs the question of what to do with the information, and opens the door to discussion of a PCI trial in high risk metastatic breast cancer...

Abstract and Link

Nomogram to Predict Subsequent Brain Metastasis in Patients With Metastatic Breast Cancer [Breast Cancer]: "Purpose

Brain metastasis is usually a fatal event in patients with stage IV breast cancer. We hypothesized that its occurrence can be predicted if a clinical nomogram can be developed, thus allowing for selection of enriched patient populations for prevention trials.

Patients and Methods

Electronic medical records of patients with metastatic breast cancer were retrospectively reviewed for the period between January 2000 and February 2007 under a study approved by the institutional review board. A multivariate logistic regression analysis of selected prognostic features was done. A nomogram to predict brain metastasis was constructed and validated in a cohort of 128 patients with brain metastasis treated at the Cross Cancer Institute (Edmonton, Alberta, Canada).

Results

Of 2,136 patients with breast cancer, 362 developed subsequent brain metastasis. Age, grade, negative status of estrogen receptor and human epidermal growth factor receptor 2, number of metastatic sites (one v > one), and short disease-free survival were significantly and independently associated with subsequent brain metastasis. The nomogram showed an area under the receiver operating characteristic curve (AUC) of 0.68 (95% CI, 0.66 to 0.69) in the training set. The validation set showed a good discrimination with an AUC of 0.74 (95% CI, 0.70 to 0.79). The nomogram was well calibrated, with no significant difference between the predicted and the observed probabilities.

Conclusion

We have developed a robust tool that is able to predict subsequent brain metastasis in patients with breast cancer with nonbrain metastatic disease. Selection of an enriched patient population at high risk for brain metastasis will facilitate the design of trials aiming at its prevention.

"

CHART results in H&N cancer

An interesting article in the Red Journal about CHART in H&N cancer. Essentially this randomized trial saw no difference in disease outcomes with CHART compared to conventional fractionation, but a reduction in toxicity, as one would expect with reduced dose per fraction. Of course this CHART is a logistical challenge to many rad onc departments, and this doesn't address the larger issue of chemotherapy (see other post about RTOG 0129). I would also venture that the doses are a little low compared to the standard 70-80Gy often uses without chemo for advanced disease.

Link and Abstract:

Mature Results of a Randomized Trial of Accelerated Hyperfractionated Versus Conventional Radiotherapy in Head-and-Neck Cancer: "Purpose: To evaluate long-term late adverse events and treatment outcome of a randomized, multicenter Phase III trial of continuous, hyperfractionated, accelerated radiotherapy (CHART) compared with conventional radiotherapy (CRT) in 918 patients with advanced squamous cell carcinomas of the head and neck.Methods and Materials: Survival estimates were obtained for locoregional relapse-free survival, local relapse-free survival, overall survival, disease-specific survival, disease-free survival and for late adverse events.Results: The 10-year estimates (±1 standard error) for locoregional relapse-free survival, overall survival, disease-free survival, and disease-specific survival were 43% ± 2% for CHART and 50% ± 3% with CRT (log-rank p = 0.2); 26% ± 2% and 29% ± 3% (p = 0.4), respectively; 41% ± 2% and 46% ± 3% (p = 0.3), respectively; and 56% ± 3% and 58% ± 3% (p = 0.5), respectively. There was a small but significant reduction in the incidence of slight or worse and moderate or worse epidermal adverse events with CHART (p = 0.002 to 0.05). Severe xerostomia, laryngeal edema, and mucosal necrosis were also significantly lower with CHART (p = 0.02 to 0.05).Conclusions: Despite the reduction in total dose from 66 Gy to 54 Gy, control of locoregional disease and survival with CHART were similar to those with CRT. These findings, together with the low incidence of long-term severe adverse events, suggest that CHART is a treatment option for patients with low-risk disease and for those unable to withstand the toxicity of concurrent chemoradiotherapy."

RTOG 0129 - Accelerated concomitant boost confers no benefit if chemo is used in H&N cancers

Another abstract sees the light of day in the Red Journal:

~700 patients with stage III and IV H&N cancer were randomized to either altered fracitonation (concomitant boost) vs standard fractionation with concurrent CDDP. No differences were seen in any of the endpoints (toxicity, OS, DFS, LRC, or DM). This confirms findings from the GORTEC trial that CDDP may supersede the effect of altered fractionation in the treatment of H&N cancers. Again - the manuscript will be eagerly awaited...

Link

A Phase III Trial to Test Accelerated Versus Standard Fractionation in Combination with Concurrent Cisplatin for Head and Neck Carcinomas (RTOG 0129): Report of Efficacy and Toxicity: "A phase III trial was completed to test the efficacy-toxicity of combining cisplatin with an accelerated concomitant boost (AFX-C) versus standard fractionation (SFX) in locally advanced head and neck carcinoma (LA-HNC)."

Short Term ADT improves survival in intermediate risk prostate cancer: RTOG 94-08

The abstract for the initial results of RTOG 9408 are published in the Red Journal - ~2000 patients with T1b-2b prostate cancer were randomized to 66.6Gy +/- 4 months of ADT starting 2 months prior to RT start. 61% had GS 6 or less, about half were T1, half T2. Result demonstrated a statistically significant improvement in OS at 12years (51% vs 46%, p=0.03).

Of course one critique is that the overall RT dose is too low by todays standards, but this supports the D'Amico trial's findings and confirms potential benefit of brief ADT in intermediate and even some low risk patients. The manuscript will be eagerly awaited...

Link:

Short-term Endocrine Therapy Prior to and during Radiation Therapy Improves Overall Survival in Patients with T1b-T2b Adenocarcinoma of the Prostate and PSA ≤ 20: Initial Results of RTOG 94-08: "To test if short-term endocrine therapy prior to and during radiation therapy will improve overall survival in patients with good prognosis, locally confined, adenocarcinoma of the prostate."

NSCLC chemo meta-analysis

In the Lancet this week:

Two meta-analyses looking at the absolute benefit of chemo after surgery both with and without adjuvant radiotherapy. They found similar results in both settings with HR hovering aound 0.88 for overall survival, corresponding to a 4% absolute benefit in both groups at 5 years.

Link:

[Articles] Adjuvant chemotherapy, with or without postoperative radiotherapy, in operable non-small-cell lung cancer: two meta-analyses of individual patient data: "Many randomised controlled trials have investigated the effect of adjuvant chemotherapy in operable non-small-cell lung cancer. We undertook two comprehensive systematic reviews and meta-analyses to establish the effects of adding adjuvant chemotherapy to surgery, or to surgery plus radiotherapy."