Friday, July 30, 2010

Matched Pair Analysis Comparing Surgery Followed By Radiotherapy and Radiotherapy Alone for Metastatic Spinal Cord Compression [Palliative and Supportive Care]

In the JCO this week:

A retrospective international series, calls into question the results of the Patchell Study of decompressive surgery before RT in spinal cord compression. The Patchell study demostrated a significant benefit in terms of recovery of amulation in addition to other neurologic endpoints, as well as survival. This study matched pairs of 1:2 for surgery + RT and RT alone, and, in short, found no differences. The authors of this JCO article conclude that the population in the randomized trial was very selected, and that perhaps, in a broader population the question should be subject to another randomized trial.

I don't know how much enthusiasm there would be to run such a trial again, and at least in our experience, surgery is reserved for the most selected population, mostly likely to benefit (single tumors, controlled primaries, etc.). Additionally, like the Patchell study, laminectomies (which make up a fair portion of the retrospective study) are not routinely recommended, as direct decompressions are a superior surgery in these situation.

Nonetheless, this is an interesting article looking at a common situation that has little randomized data to guide treatment.

Link and Abstract

Matched Pair Analysis Comparing Surgery Followed By Radiotherapy and Radiotherapy Alone for Metastatic Spinal Cord Compression [Palliative and Supportive Care]: "Purpose

The appropriate treatment for MSCC is controversial. A small randomized trial showed that decompressive surgery followed by radiotherapy was superior to radiotherapy alone. That study was limited to highly selected patients. Additional studies comparing surgery plus radiotherapy to radiotherapy could better clarify the role of surgery.


Data from 108 patients receiving surgery plus radiotherapy were matched to 216 patients (1:2) receiving radiotherapy alone. Groups were matched for 11 potential prognostic factors and compared for post-treatment motor function, ambulatory status, regaining ambulatory status, local control, and survival. Subgroup analyses were performed for patients receiving adequate surgery (direct decompressive surgery plus stabilization of involved vertebrae), patients receiving laminectomy, patients with solid tumors, patients with solid tumors receiving adequate surgery, and patients with solid tumors receiving laminectomy.


Improvement of motor function occurred in 27% of patients after surgery plus radiotherapy and 26% after radiotherapy alone (P = .92). Post-treatment ambulatory rates were 69% after surgery plus radiotherapy and 68% after radiotherapy alone (P = .99). Of the nonambulatory patients, 30% and 26%, respectively, (P = .86) regained ambulatory status after treatment. One-year local control rates were 90% after surgery plus radiotherapy and 91% after radiotherapy alone (P = .48). One-year overall survival rates were 47% and 40%, respectively (P = .50). The subgroup analyses did not show significant differences between both groups. Surgery-related complications occurred in 11% of patients.


In this study, the outcomes of the end points evaluated after radiotherapy alone appeared similar to those of surgery plus radiotherapy. A new randomized trial comparing both treatments is justified.


Friday, July 9, 2010

Lancet: IORT for Breast - the TARGIT-A trial

In the Lancet

Previously available online and presented at ASCO, the TARGIT-A trial is published in Lancet today. To briefly recap - this multinational randomized trial looked at conventional fracitonation vs 20Gy in a single treatment intraoperatively. 4 year data shows similar local control, with potentially slightly less toxicity, and clearly less time and resources devoted. While the time points evaluated are still too early to replace the standard of care in all patients, in selected patients, this approach is potentially very attractive.


[Articles] Targeted intraoperative radiotherapy versus whole breast radiotherapy for breast cancer (TARGIT-A trial): an international, prospective, randomised, non-inferiority phase 3 trial: "After breast-conserving surgery, 90% of local recurrences occur within the index quadrant despite the presence of multicentric cancers elsewhere in the breast. Thus, restriction of radiation therapy to the tumour bed during surgery might be adequate for selected patients. We compared targeted intraoperative radiotherapy with the conventional policy of whole breast external beam radiotherapy."

JCO: RT for advanced HD and unfavorable early HD

This weeks JCO:

A very compelling analysis is presented looking at non-randomized results with consolidation RT after chemotherapy in a prospective chemo trial for advanced stage and early unfavorable Hodgkin Disease. Despite the fact that the RT group had more "bulky" disease and more incomplete responders, a benefit was seen across the board for PFS and OS, with HRs for all subgroups <= to 0.5. Also interestingly they looked at dose (see figure 5), showing no compelling dose response beyond 30Gy.

Link and Abstract

Consolidation Radiotherapy in Patients With Advanced Hodgkin's Lymphoma: Survival Data From the UKLG LY09 Randomized Controlled Trial (ISRCTN97144519) [Hematologic Malignancies]: "Purpose

This study analyzed the outcomes of nonrandomized consolidation radiotherapy (RT) given after chemotherapy in the initial treatment of advanced Hodgkin's lymphoma (HL). The results were collected prospectively within a randomized controlled trial of induction chemotherapy.

Patients and Methods

Patients were randomly assigned between doxorubicin, bleomycin, vinblastine, and dacarbazine and one of two prespecified multidrug regimens. At least six cycles of chemotherapy were planned, with up to eight for patients showing slower response. Involved-field RT was recommended for incomplete response to chemotherapy or bulk disease at presentation. The primary outcome measure was progression-free survival (PFS), landmarked from the end of chemotherapy.


Among 807 patients randomly assigned, 702 achieved objective response. Postchemotherapy RT for consolidation was reported in 300 (43%). With median follow-up of 6.9 years, 161 PFS events and 83 deaths were reported. Baseline characteristics showed more patients with bulk disease having RT (190 [63%] v 111 [28%]) and only partial response after chemotherapy (150 [50%] v 36 [9%]). Other baseline characteristics were similar. PFS was superior for patients having RT (hazard ratio [HR], 0.43; 95% CI, 0.30 to 0.60) with 5-year PFS 71% without RT, 86% with RT. A similar advantage was seen for overall survival (HR, 0.47; 95% CI, 0.29 to 0.77). There was no evidence of heterogeneity of treatment effect across subgroups.


Patients who received consolidation RT apparently had better outcomes, consistently across all prognostic groups which persisted in multivariate analysis. This suggests that RT contributes significantly to the cure rate for advanced HL, although patient selection for combined modality treatment requires better definition in prospective trials.


JCO: Gefitinib integration into CTRT for H&N cancer

JCO this week:

An interesting phase II looking at the integration of gefitinib (an EGFR TKI), with concurrent chemoradiotherapy. The overall approach is different than what many centers would call standard treatment with induction carbo/paclitaxel, followed by 5FU, HU, and gefinitib with BID RT, then continuing gefitinib afterwards. The results however are good in comparison to historical controls, and it will be very interesting to see how integration of EGFR inhibition in ongoing phase III trials will fair when result mature over the next ~5 years.

Link and abstract

Epidermal Growth Factor Receptor Inhibitor Gefitinib Added to Chemoradiotherapy in Locally Advanced Head and Neck Cancer [Head and Neck Cancer]: "Purpose

Assess efficacy and toxicity of gefitinib, an epidermal growth factor receptor (EGFR) inhibitor, added to, and in maintenance after, concurrent chemoradiotherapy (CCRT) in locally advanced head and neck cancer (LA-HNC) and correlate outcomes with EGFR gene copy number alterations.

Patients and Methods

Patients with stage III to IV LA-HNC received two cycles of carboplatin/paclitaxel induction chemotherapy (IC) followed by split-course CCRT with fluorouracil, hydroxyurea, twice daily radiotherapy (FHX), and gefitinib (250 mg daily) followed by continued gefitinib for 2 years total. The primary end point was complete response (CR) rate after CCRT. EGFR gene copy number was assessed by fluorescent in situ hybridization.


Sixty-nine patients (66 with stage IV disease, 37 with oropharynx primary tumors, and 67 with performance status 0 to 1) were enrolled with a median age of 55 years. Predominant grade 3 or 4 toxicities during IC and CCRT were neutropenia (n = 20) and in-field mucositis (n = 59) and dermatitis (n = 23), respectively. CR rate after CCRT was 90%. After median follow-up of 3.5 years, 4-year overall, progression-free, and disease-specific survival rates were 74%, 72%, and 89%, respectively. To date, one patient has developed a second primary tumor in the aerodigestive tract. In 31 patients with available tissue, high EGFR gene copy number was associated with worse overall survival (P = .02).


Gefitinib can be administered with FHX and as maintenance therapy for at least 2 years, demonstrating CR and survival rates that compare favorably with prior experience. High EGFR gene copy number may be associated with poor outcome in patients with LA-HNC treated with this regimen.