Monday, December 13, 2010
Tuesday, November 16, 2010
Friday, October 29, 2010
Patients and Methods
Tuesday, October 12, 2010
The role of adjuvant chemoradiotherapy (CRT) in resectable pancreatic cancer is still debated. This randomized phase II intergroup study explores the feasibility and tolerability of a gemcitabine-based CRT regimen after R0 resection of pancreatic head cancer.Patients and Methods
Within 8 weeks after surgery, patients were randomly assigned to receive either four cycles of gemcitabine (control arm) or gemcitabine for two cycles followed by weekly gemcitabine with concurrent radiation (50.4 Gy; CRT arm). The primary objective was to exclude a < 60% treatment completion and a > 40% rate of grade 4 hematologic or GI toxicity in the CRT arm with type I and II errors of 10%. Secondary end points were late toxicity, disease-free survival (DFS), and overall survival (OS).Results
Between September 2004 and January 2007, 90 patients were randomly assigned (45:45). Patient characteristics were similar in both arms. Treatment was completed per protocol by 86.7% and 73.3% (80% CI, 63.1% to 81.9%; 95% CI, 58.1% to 85.4%) in the control and CRT arms, respectively, and grade 4 toxicity was 0% and 4.7% (two of 43; 80% CI, 1.2% to 11.9%), respectively. In the CRT arm, three patients experienced grade 3–related late toxicity. Median DFS was 12 months in the CRT arm and 11 months in the control arm. Median OS was 24 months in both arms. First local recurrence was less frequent in the CRT arm (11% v 24%).Conclusion
Adjuvant gemcitabine-based CRT is feasible, well-tolerated, and not deleterious; adding this treatment to full-dose adjuvant gemcitabine after resection of pancreatic cancer should be evaluated in a phase III trial."
Friday, October 1, 2010
Monday, September 20, 2010
Intensified Chemotherapy and Dose-Reduced Involved-Field Radiotherapy in Patients With Early Unfavorable Hodgkin's Lymphoma: Final Analysis of the German Hodgkin Study Group HD11 Trial [Hematologic Malignancies]
This was a 2x2 trial, looking at escalating chemotherapy (comparing the standard ABVD to BEACOPP), and de-escalating RT (30Gy to 20Gy). Unfortunately, the answer was not clear cut, with both of the comparisons being negative (i.e. BEACOPP was not superior to ABVD, and 20Gy was not "non-inferior" to 30Gy). Of course the temptation is to the look at each of the four arms individually - in which it was observed that the escalation of BEACOPP may conterbalance the descalation of 20Gy, but in the end, one must look on this as a unplanned subgroup analysis.
Combined-modality treatment consisting of four to six cycles of chemotherapy followed by involved-field radiotherapy (IFRT) is the standard of care for patients with early unfavorable Hodgkin's lymphoma (HL). It is unclear whether treatment results can be improved with more intensive chemotherapy and which radiation dose needs to be applied.Patients and Methods
Patients age 16 to 75 years with newly diagnosed early unfavorable HL were randomly assigned in a 2 x 2 factorial design to one of the following treatment arms: four cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) + 30 Gy of IFRT; four cycles of ABVD + 20 Gy of IFRT; four cycles of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPPbaseline) + 30 Gy of IFRT; or four cycles of BEACOPPbaseline + 20 Gy of IFRT.Results
With a total of 1,395 patients included, the freedom from treatment failure (FFTF) at 5 years was 85.0%, overall survival was 94.5%, and progression-free survival was 86.0%. BEACOPPbaseline was more effective than ABVD when followed by 20 Gy of IFRT (5-year FFTF difference, 5.7%; 95% CI, 0.1% to 11.3%). However, there was no difference between BEACOPPbaseline and ABVD when followed by 30 Gy of IFRT (5-year FFTF difference, 1.6%; 95% CI, –3.6% to 6.9%). Similar results were observed for the radiotherapy question; after four cycles of BEACOPPbaseline, 20 Gy was not inferior to 30 Gy (5-year FFTF difference, –0.8%; 95% CI, –5.8% to 4.2%), whereas inferiority of 20 Gy cannot be excluded after four cycles of ABVD (5-year FFTF difference, –4.7%; 95% CI, –10.3% to 0.8%). Treatment-related toxicity occurred more often in the arms with more intensive therapy.Conclusion
Moderate dose escalation using BEACOPPbaseline did not significantly improve outcome in early unfavorable HL. Four cycles of ABVD should be followed by 30 Gy of IFRT.
The current standard therapy for patients with diffuse large B-cell lymphoma (DLBCL) is rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). The role of consolidative radiation therapy (RT) in the setting of R-CHOP chemotherapy is not well reported. This retrospective analysis is an attempt to clarify this role.Patients and Methods
Subjects were 469 patients with histologically confirmed DLBCL treated between January 2001 and December 2007. Variables including age, sex, Ann Arbor disease stage, bulky disease status, standardized uptake values (SUVs) on positron emission tomography (PET), International Prognostic Index (IPI), and Ki67 staining (proliferation).Results
Of 469 patients, 190 (40.5%) had stage I or II disease and 279 (59.5%) had stage III or IV disease, 327 (70%) had at least six cycles of R-CHOP, and 142 (30.2%) had involved-field RT (dose, 30 to 39.6 Gy) after complete response to chemotherapy. Median follow-up was 36 months (range, 8 to 85 months). Multivariate analysis showed that RT (P < .0001), IPI score (P = .001), response to therapy (P = .001), use of six to eight cycles of R-CHOP (P < .001), and combined presence (P = .006) or absence (P = .025) of high Ki67, high PET SUV, and bulky disease influenced overall survival (OS) and progression-free survival (PFS). Matched-pair analyses of patients who received six to eight cycles of R-CHOP with stage I or II disease (44 pairs) and all stages (74 pairs) indicated that RT improved OS (hazard ratio [HR], 0.52 and 0.29, respectively) and PFS (HR, 0.45 and 0.24, respectively) compared with no RT.Conclusion
This study showed significant improvements in OS and PFS among patients who received consolidation RT after R-CHOP chemotherapy for DLBCL."
Tuesday, September 14, 2010
Adjuvant Chemotherapy With Fluorouracil Plus Folinic Acid vs Gemcitabine Following Pancreatic Cancer Resection: A Randomized Controlled Trial [Original Contribution]
Context Adjuvant fluorouracil has been shown to be of benefit for patients with resected pancreatic cancer. Gemcitabine is known to be the most effective agent in advanced disease as well as an effective agent in patients with resected pancreatic cancer.
Objective To determine whether fluorouracil or gemcitabine is superior in terms of overall survival as adjuvant treatment following resection of pancreatic cancer.
Design, Setting, and Patients The European Study Group for Pancreatic Cancer (ESPAC)-3 trial, an open-label, phase 3, randomized controlled trial conducted in 159 pancreatic cancer centers in Europe, Australasia, Japan, and Canada. Included in ESPAC-3 version 2 were 1088 patients with pancreatic ductal adenocarcinoma who had undergone cancer resection; patients were randomized between July 2000 and January 2007 and underwent at least 2 years of follow-up.
Interventions Patients received either fluorouracil plus folinic acid (folinic acid, 20 mg/m2, intravenous bolus injection, followed by fluorouracil, 425 mg/m2 intravenous bolus injection given 1-5 days every 28 days) (n = 551) or gemcitabine (1000 mg/m2 intravenous infusion once a week for 3 of every 4 weeks) (n = 537) for 6 months.
Main Outcome Measures Primary outcome measure was overall survival; secondary measures were toxicity, progression-free survival, and quality of life.
Results Final analysis was carried out on an intention-to-treat basis after a median of 34.2 (interquartile range, 27.1-43.4) months' follow-up after 753 deaths (69%). Median survival was 23.0 (95% confidence interval [CI], 21.1-25.0) months for patients treated with fluorouracil plus folinic acid and 23.6 (95% CI, 21.4-26.4) months for those treated with gemcitabine (21 = 0.7; P = .39; hazard ratio, 0.94 [95% CI, 0.81-1.08]). Seventy-seven patients (14%) receiving fluorouracil plus folinic acid had 97 treatment-related serious adverse events, compared with 40 patients (7.5%) receiving gemcitabine, who had 52 events (P < .001). There were no significant differences in either progression-free survival or global quality-of-life scores between the treatment groups.
Conclusion Compared with the use of fluorouracil plus folinic acid, gemcitabine did not result in improved overall survival in patients with completely resected pancreatic cancer.
Trial Registration clinicaltrials.gov Identifier: NCT00058201"
Wednesday, September 1, 2010
Context Mastectomy and salpingo-oophorectomy are widely used by carriers of BRCA1 or BRCA2 mutations to reduce their risks of breast and ovarian cancer.
Objective To estimate risk and mortality reduction stratified by mutation and prior cancer status.
Design, Setting, and Participants Prospective, multicenter cohort study of 2482 women with BRCA1 or BRCA2 mutations ascertained between 1974 and 2008. The study was conducted at 22 clinical and research genetics centers in Europe and North America to assess the relationship of risk-reducing mastectomy or salpingo-oophorectomy with cancer outcomes. The women were followed up until the end of 2009.
Main Outcomes Measures Breast and ovarian cancer risk, cancer-specific mortality, and overall mortality.
Results No breast cancers were diagnosed in the 247 women with risk-reducing mastectomy compared with 98 women of 1372 diagnosed with breast cancer who did not have risk-reducing mastectomy. Compared with women who did not undergo risk-reducing salpingo-oophorectomy, women who underwent salpingo-oophorectomy had a lower risk of ovarian cancer, including those with prior breast cancer (6% vs 1%, respectively; hazard ratio [HR], 0.14; 95% confidence interval [CI], 0.04-0.59) and those without prior breast cancer (6% vs 2%; HR, 0.28 [95% CI, 0.12-0.69]), and a lower risk of first diagnosis of breast cancer in BRCA1 mutation carriers (20% vs 14%; HR, 0.63 [95% CI, 0.41-0.96]) and BRCA2 mutation carriers (23% vs 7%; HR, 0.36 [95% CI, 0.16-0.82]). Compared with women who did not undergo risk-reducing salpingo-oophorectomy, undergoing salpingo-oophorectomy was associated with lower all-cause mortality (10% vs 3%; HR, 0.40 [95% CI, 0.26-0.61]), breast cancer–specific mortality (6% vs 2%; HR, 0.44 [95% CI, 0.26-0.76]), and ovarian cancer–specific mortality (3% vs 0.4%; HR, 0.21 [95% CI, 0.06-0.80]).
Conclusions Among a cohort of women with BRCA1 and BRCA2 mutations, the use of risk-reducing mastectomy was associated with a lower risk of breast cancer; risk-reducing salpingo-oophorectomy was associated with a lower risk of ovarian cancer, first diagnosis of breast cancer, all-cause mortality, breast cancer–specific mortality, and ovarian cancer–specific mortality."
Tuesday, August 31, 2010
Monday, August 2, 2010
Friday, July 30, 2010
Matched Pair Analysis Comparing Surgery Followed By Radiotherapy and Radiotherapy Alone for Metastatic Spinal Cord Compression [Palliative and Supportive Care]
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.Methods
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.Results
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.Conclusion
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
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.Results
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.Conclusion
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."
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.Results
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).Conclusion
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."
Friday, June 18, 2010
To report the impact of radiotherapy quality on outcome in a large international phase III trial evaluating radiotherapy with concurrent cisplatin plus tirapazamine for advanced head and neck cancer.Patients and Methods
The protocol required interventional review of radiotherapy plans by the Quality Assurance Review Center (QARC). All plans and radiotherapy documentation underwent post-treatment review by the Trial Management Committee (TMC) for protocol compliance. Secondary review of noncompliant plans for predicted impact on tumor control was performed. Factors associated with poor protocol compliance were studied, and outcome data were analyzed in relation to protocol compliance and radiotherapy quality.Results
At TMC review, 25.4% of the patients had noncompliant plans but none in which QARC-recommended changes had been made. At secondary review, 47% of noncompliant plans (12% overall) had deficiencies with a predicted major adverse impact on tumor control. Major deficiencies were unrelated to tumor subsite or to T or N stage (if N+), but were highly correlated with number of patients enrolled at the treatment center (< five patients, 29.8%; ≥ 20 patients, 5.4%; P < .001). In patients who received at least 60 Gy, those with major deficiencies in their treatment plans (n = 87) had a markedly inferior outcome compared with those whose treatment was initially protocol compliant (n = 502): –2 years overall survival, 50% v 70%; hazard ratio (HR), 1.99; P < .001; and 2 years freedom from locoregional failure, 54% v 78%; HR, 2.37; P < .001, respectively.Conclusion
These results demonstrate the critical importance of radiotherapy quality on outcome of chemoradiotherapy in head and neck cancer. Centers treating only a few patients are the major source of quality problems."
Promising results in a randomized phase II trial with the hypoxic cytotoxin tirapazamine (TPZ) combined with cisplatin (CIS) and radiation led to this phase III trial.Patients and Methods
Patients with previously untreated stage III or IV (excluding T1-2N1 and M1) squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx were randomly assigned to receive definitive radiotherapy (70 Gy in 7 weeks) concurrently with either CIS (100 mg/m2) on day 1 of weeks 1, 4, and 7 or CIS (75 mg/m2) plus TPZ (290 mg/m2/d) on day 1 of weeks 1, 4, and 7 and TPZ alone (160 mg/m2/d) on days 1, 3, and 5 of weeks 2 and 3 (TPZ/CIS). The primary end point was overall survival (OS). The planned sample size was 850, estimated to result in 334 deaths, which would provide 90% power to detect a difference in 2-year survival rates of 60% v 70% for CIS versus TPZ/CIS, respectively (hazard ratio = 0.69).Results
Eight hundred sixty-one patients were accrued from 89 sites in 16 countries. In an intent-to-treat analysis, the 2-year OS rates were 65.7% for CIS and 66.2% for TPZ/CIS (TPZ/CIS – CIS: 95% CI, –5.9% to 6.9%). There were no significant differences in failure-free survival, time to locoregional failure, or quality of life as measured by Functional Assessment of Cancer Therapy–Head and Neck.Conclusions
We found no evidence that the addition of TPZ to chemoradiotherapy, in patients with advanced head and neck cancer not selected for the presence of hypoxia, improves OS."
Monday, June 14, 2010
Sunday, June 6, 2010
Saturday, June 5, 2010
Wednesday, June 2, 2010
Tuesday, June 1, 2010
Friday, May 21, 2010
I have been shying away from hypofx in G3 patients until now, but this data will make me much more comfortable offering it to our patients.
Tuesday, May 4, 2010
The previous individual patient data meta-analyses of chemotherapy in locally advanced non–small-cell lung cancer (NSCLC) showed that adding sequential or concomitant chemotherapy to radiotherapy improved survival. The NSCLC Collaborative Group performed a meta-analysis of randomized trials directly comparing concomitant versus sequential radiochemotherapy.Methods
Systematic searches for trials were undertaken, followed by central collection, checking, and reanalysis of updated individual patient data. Results from trials were combined using the stratified log-rank test to calculate pooled hazard ratios (HRs). The primary outcome was overall survival; secondary outcomes were progression-free survival, cumulative incidences of locoregional and distant progression, and acute toxicity.Results
Of seven eligible trials, data from six trials were received (1,205 patients, 92% of all randomly assigned patients). Median follow-up was 6 years. There was a significant benefit of concomitant radiochemotherapy on overall survival (HR, 0.84; 95% CI, 0.74 to 0.95; P = .004), with an absolute benefit of 5.7% (from 18.1% to 23.8%) at 3 years and 4.5% at 5 years. For progression-free survival, the HR was 0.90 (95% CI, 0.79 to 1.01; P = .07). Concomitant treatment decreased locoregional progression (HR, 0.77; 95% CI, 0.62 to 0.95; P = .01); its effect was not different from that of sequential treatment on distant progression (HR, 1.04; 95% CI, 0.86 to 1.25; P = .69). Concomitant radiochemotherapy increased acute esophageal toxicity (grade 3-4) from 4% to 18% with a relative risk of 4.9 (95% CI, 3.1 to 7.8; P < .001). There was no significant difference regarding acute pulmonary toxicity.Conclusion
Concomitant radiochemotherapy, as compared with sequential radiochemotherapy, improved survival of patients with locally advanced NSCLC, primarily because of a better locoregional control, but at the cost of manageable increased acute esophageal toxicity."
Friday, April 23, 2010
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."
Thursday, April 22, 2010
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."
Friday, April 16, 2010
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...
Friday, April 9, 2010
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.
Wednesday, March 31, 2010
Neoadjuvant chemoradiotherapy is considered a standard approach for T3-4 M0 rectal cancer. In this situation, we compared neoadjuvant radiotherapy plus capecitabine with dose-intensified radiotherapy plus capecitabine and oxaliplatin.Patients and Methods
We randomly assigned patients to receive 5 weeks of treatment with radiotherapy 45 Gy/25 fractions with concurrent capecitabine 800 mg/m2 twice daily 5 days per week (Cap 45) or radiotherapy 50 Gy/25 fractions with capecitabine 800 mg/m2 twice daily 5 days per week and oxaliplatin 50 mg/m2 once weekly (Capox 50). The primary end point was complete sterilization of the operative specimen (ypCR).Results
Five hundred ninety-eight patients were randomly assigned to receive Cap 45 (n = 299) or Capox 50 (n = 299). More preoperative grade 3 to 4 toxicity occurred in the Capox 50 group (25 v 1%; P < .001). Surgery was performed in 98% of patients in both groups. There were no differences between groups in the rate of conservative surgery (75%) or postoperative deaths at 60 days (0.3%). The ypCR rate was 13.9% with Cap 45 and 19.2% with Capox 50 (P = .09). When ypCR was combined with yp few residual cells, the rate was respectively 28.9% with Cap 45 and 39.4% with Capox 50 (P = .008). The rate of positive circumferential rectal margins (between 0 and 2 mm) was 19.3% with Cap 45 and 9.9% with Capox 50 (P = .02).Conclusion
The benefit of oxaliplatin was not demonstrated and this drug should not be used with concurrent irradiation. Cap 50 merits investigation for T3-4 rectal cancers."
Tuesday, March 16, 2010
Stereotactic Body Radiation Therapy for Inoperable Early Stage Lung Cancer [Preliminary Communication]
Context Patients with early stage but medically inoperable lung cancer have a poor rate of primary tumor control (30%-40%) and a high rate of mortality (3-year survival, 20%-35%) with current management.
Objective To evaluate the toxicity and efficacy of stereotactic body radiation therapy in a high-risk population of patients with early stage but medically inoperable lung cancer.
Design, Setting, and Patients Phase 2 North American multicenter study of patients aged 18 years or older with biopsy-proven peripheral T1-T2N0M0 non–small cell tumors (measuring <5 cm in diameter) and medical conditions precluding surgical treatment. The prescription dose was 18 Gy per fraction x 3 fractions (54 Gy total) with entire treatment lasting between 11/2 and 2 weeks. The study opened May 26, 2004, and closed October 13, 2006; data were analyzed through August 31, 2009.
Main Outcome Measures The primary end point was 2-year actuarial primary tumor control; secondary end points were disease-free survival (ie, primary tumor, involved lobe, regional, and disseminated recurrence), treatment-related toxicity, and overall survival.
Results A total of 59 patients accrued, of which 55 were evaluable (44 patients with T1 tumors and 11 patients with T2 tumors) with a median follow-up of 34.4 months (range, 4.8-49.9 months). Only 1 patient had a primary tumor failure; the estimated 3-year primary tumor control rate was 97.6% (95% confidence interval [CI], 84.3%-99.7%). Three patients had recurrence within the involved lobe; the 3-year primary tumor and involved lobe (local) control rate was 90.6% (95% CI, 76.0%-96.5%). Two patients experienced regional failure; the local-regional control rate was 87.2% (95% CI, 71.0%-94.7%). Eleven patients experienced disseminated recurrence; the 3-year rate of disseminated failure was 22.1% (95% CI, 12.3%-37.8%). The rates for disease-free survival and overall survival at 3 years were 48.3% (95% CI, 34.4%-60.8%) and 55.8% (95% CI, 41.6%-67.9%), respectively. The median overall survival was 48.1 months (95% CI, 29.6 months to not reached). Protocol-specified treatment-related grade 3 adverse events were reported in 7 patients (12.7%; 95% CI, 9.6%-15.8%); grade 4 adverse events were reported in 2 patients (3.6%; 95% CI, 2.7%-4.5%). No grade 5 adverse events were reported.
Conclusion Patients with inoperable non–small cell lung cancer who received stereotactic body radiation therapy had a survival rate of 55.8% at 3 years, high rates of local tumor control, and moderate treatment-related morbidity."
Tuesday, March 9, 2010
The validity of sentinel lymph node biopsy (SLNB) for T1 or T2, clinically N0, oral cancer was tested by correlation of sentinel node pathologic status with that of nodes within the completion neck dissection.Methods
This prospective, cooperative group trial involved 25 institutions over a 3-year period. One hundred forty patients with invasive oral cancers, stage T1 and T2, N0 including 95 cancers of the tongue, 26 of the floor of mouth, and 19 other oral cancers were studied. The study excluded lesions with diameter smaller than 6 mm or minimal invasion. Imaging was used to exclude nonpalpable gross nodal disease. Patients underwent injection of the lesion with 99mTc-sulfur colloid, nuclear imaging, narrow-exposure SLNB, and completion selective neck dissection. The major end point was the negative-predictive value (NPV) of SLNB.Results
In the 106 SLNBs, which were found to be pathologically and clinically node-negative by routine hematoxylin and eosin stain, 100 patients were found to have no other pathologically positive nodes, corresponding to a NPV of 94%. With additional sectioning and immunohistochemistry, NPV was improved to 96%. In the forty patients with proven cervical metastases, the true-positive rate was 90.2% and was superior for tongue tumors relative to floor of mouth. For T1 lesions, metastases were correctly identified in 100%.Conclusion
For T1 or T2 N0 oral squamous cell carcinoma, SLNB with step sectioning and immunohistochemistry, performed by surgeons of mixed experience levels, correctly predicted a pathologically negative neck in 96% of patients (NPV, 96%)."
Patients and Methods
In total, 166 patients with stage III or medically inoperable stage I to II non–small-cell lung cancer, WHO performance status 0 to 2, a forced expiratory volume at 1 second and diffusing capacity of lungs for carbon monoxide ≥ 30% were included. Patients were irradiated using an individualized prescribed total tumor dose (TTD) based on normal tissue dose constraints (mean lung dose, 19 Gy; maximal spinal cord dose, 54 Gy) up to a maximal TTD of 79.2 Gy in 1.8 Gy fractions twice daily. Only sequential chemoradiation was administered. The primary end point was overall survival (OS), and the secondary end point was toxicity according to Common Terminology Criteria of Adverse Events (CTCAE) v3.0.Results
The median prescribed TTD was 64.8 Gy (standard deviation, ± 11.4 Gy) delivered in 25 ± 5.8 days. With a median follow-up of 31.6 months, the median OS was 21.0 months with a 1-year OS of 68.7% and a 2-year OS of 45.0%. Multivariable analysis showed that only a large gross tumor volume significantly decreased OS (P < .001). Both acute (grade 3, 21.1%; grade 4, 2.4%) and late toxicity (grade 3, 4.2%; grade 4, 1.8%) were acceptable.Conclusion
Individualized prescribed radical radiotherapy based on normal tissue constraints with sequential chemoradiation shows survival rates that come close to results of concurrent chemoradiation schedules, with acceptable acute and late toxicity. A prospective randomized study is warranted to further investigate its efficacy."