F. Laurie

Effect of Addition of Adjuvant Paclitaxel on Radiotherapy Delivery and Locoregional Control of Node-Positive Breast Cancer: Cancer and Leukemia Group B 9344

PURPOSEnWe compared radiotherapy (RT) delivery and locoregional control in patients with node-positive breast cancer randomly assigned on Cancer and Leukemia Group B 9344 to receive adjuvant doxorubicin/cyclophosphamide (AC) with patients assigned to receive AC followed by paclitaxel (AC+T).nnnMETHODSnEligible patients were randomly assigned to receive adjuvant AC versus AC+T chemotherapy. RT was required if breast-conserving surgery was performed but was elective after mastectomy. Information about RT delivery was retrospectively collected. Cumulative incidence of locoregional recurrence (LRR), use of elective RT, and RT delivery were compared between treatment arms.nnnRESULTSnFor patients treated with breast-conserving surgery and RT, the 5-year cumulative incidence of isolated LRR was 9.7% in the AC arm and 3.7% in the AC+T arm (P = .04) and of LRR as any component of failure was 12.9% versus 6.1%, respectively (P = .04). Although LRR rates in patients who did not receive postmastectomy RT were lower in the AC+T arm, the difference was not statistically significant. Despite the lack of protocol guidelines, RT use did not differ between arms, nor did RT dose, treatment interruption, or completion.nnnCONCLUSIONnDespite the delay to RT during additional chemotherapy, adjuvant AC+T afforded better local control than AC alone in patients treated with breast-conserving therapy. Addition of paclitaxel did not adversely affect delivery or ability to tolerate RT, as indicated by similar rates of completion of timely, full-dose RT between arms.

Hyperfractionated radiation in children with rhabdomyosarcoma—Results of an intergroup rhabdomyosarcoma pilot study

PURPOSEnThe Intergroup Rhabdomyosarcoma Study (IRS) Group initiated a pilot study (IRS IV-P) of hyperfractionated radiation (HF XRT) with chemotherapy to test the feasibility and toxicity of this combined modality approach in children with localized but nonresected (group III) and metastatic (group IV) rhabdomyosarcoma.nnnMETHODS AND MATERIALSnUsing the linear quadratic equation, and an alpha/beta ratio of 10 Gy for acute reacting tumor effect and 3 Gy for late reacting normal tissue effect, a HF XRT protocol was developed giving a total radiation dose of 59.4 Gy, in 1.10 Gy fractions, twice daily at 6-8 h intervals. All patients received chemotherapy in addition to irradiation. The radiation scheme was calculated to increase the biologically effective dose to the tumor by 10% without increasing late effects, when compared to a conventional schedule of 50.4 Gy in 1.8 Gy daily fractions. This protocol also was predicted to cause an increase in acute normal tissue effects.nnnRESULTSnFour hundred forty-nine children age 21 years and younger were eligible for the hyperfractionated radiation study of whom 297 had Group III disease and 152 had Group IV disease. A total of 117 patients were excluded from the feasibility and toxicity analysis because of progressive disease or death prior to scheduled irradiation, surgical resection, major protocol violation, treatment with brachytherapy, or missing data. Thus, 332 children were evaluable for the HF XRT protocol. Twenty-eight of the 332 (8%) were given conventional radiation because of physician preference or young age. Twenty of the 332 (6%) were not irradiated because of young age, anesthesia, or transportation problems. All nonirradiated children were < or = 3 years of age. Thus, 284 children, 86% of the evaluable population, received HF XRT. The radiation dose, number of fractions, number of days, and interfractional interval were scored as appropriate in 93% of cases. Review of radiation portals revealed that in 230 of 284 cases (81%) the radiation fields were appropriate, as per protocol. Thus, the HF XRT was feasible treatment in a multiinstitutional study. Analysis of toxicity revealed that 152 of 204 (75%) of Group III and 52 of 80 (65%) of Group IV patients experienced severe or life-threatening toxicity, explained by the addition of chemotherapy with the radiation. The majority of this toxicity was hematopoietic. Observed organ toxicity, which was potentially explained by the radiation treatment, was greatest at the end of radiation, and improved at the 6-week and 3-month evaluation periods. There were no deaths attributed to radiation toxicity and no instance of toxicity that required alteration of the radiation protocol. Thus, the treatment was not associated with toxicity that was considered excessive or unusual.nnnCONCLUSIONnThe IRS IV-P study confirms that HF XRT combined with chemotherapy is both feasible and tolerable in children with rhabdomyosarcoma. A prospective randomized trial is underway to test its efficacy as compared to conventional radiation among children also receiving concurrent chemotherapy for rhabdomyosarcoma.

Impact of High-Dose Chemotherapy on the Ability to Deliver Subsequent Local-Regional Radiotherapy for Breast Cancer: Analysis of Cancer and Leukemia Group B Protocol 9082

PURPOSEnTo report, from Cancer and Leukemia Group B Protocol 9082, the impact of high-dose cyclophosphamide, cisplatin, and BCNU (HD-CPB) vs. intermediate-dose CPB (ID-CPB) on the ability to start and complete the planned course of local-regional radiotherapy (RT) for women with breast cancer involving >or=10 axillary nodes.nnnMETHODS AND MATERIALSnFrom 1991 to 1998, 785 patients were randomized. The HD-CPB and ID-CPB arms were balanced regarding patient characteristics. The HD-CPB and ID-CPB arms were compared on the probability of RT initiation, interruption, modification, or incompleteness. The impact of clinical variables and interactions between variables were also assessed.nnnRESULTSnRadiotherapy was initiated in 82% (325 of 394) of HD-CPB vs. 92% (360 of 391) of ID-CPB patients (p = 0.001). On multivariate analyses, RT was less likely given to patients who were randomized to HD treatment (odds ratio [OR] = 0 .38, p < 0.001), older (p = 0.005), African American (p = 0.003), postmastectomy (p = 0.02), or estrogen receptor positive (p = 0.03). High-dose treatment had a higher rate of RT interruption (21% vs. 12%, p = 0.001, OR = 2.05), modification (29% vs. 14%, p = 0.001, OR = 2.46), and early termination of RT (9% vs. 2%, p = 0.0001, OR = 5.35), compared with ID.nnnCONCLUSIONnTreatment arm significantly related to initiation, interruption, modification, and early termination of RT. Patients randomized to HD-CPB were less likely to initiate RT, and of those who did, they were more likely to have RT interrupted, modified, and terminated earlier than those randomized to ID-CPB. The observed lower incidence of RT usage in African Americans vs. non-African Americans warrants further study.

Interruptions of once-daily thoracic radiotherapy do not correlate with outcomes in limited stage small cell lung cancer: analysis of CALGB phase III trial 9235.

PURPOSEnRetrospective data suggests prolonging the time to complete thoracic radiotherapy (TRT) may negatively impact tumor control and survival in limited stage small cell lung cancer (LSCLC). We examined the association between TRT duration and outcomes on a prospective phase III study.nnnMATERIAL AND METHODSnThis review included 267 patients who received protocol TRT on a phase III CALGB LSCLC study assessing the addition of tamoxifen to standard chemo-radiotherapy. TRT, to a planned dose of 50Gy in 2Gy daily fractions, was initiated with the fourth chemotherapy cycle. TRT interruptions were mandated for hematologic toxicity (granulocytes<1000/mm3 or platelets<75,000/mm3) and esophageal toxicity (dysphagia necessitating intravenous hydration).nnnRESULTSnTRT interruptions > or =3 days occurred in 115 patients (43%), most frequently during the 4th week of TRT, and did not differ between treatment arms. Hematologic toxicity and esophageal toxicity were the most frequent indications for interrupting TRT. Variables including advanced age (>70 years), gender, race, or radiotherapy treatment volume did not predict for TRT interruptions. Overall survival (OS) and local tumor control did not correlate with the administration of TRT interruptions or with TRT duration.nnnCONCLUSIONnToxicity mandated interruptions of conventional dose, once-daily, TRT may not adversely affect outcomes for patients receiving TRT concurrent with chemotherapy (cycle 4) for LSCLC. The implications for accelerated or high dose TRT regimens are not clear.

Imaging and Data Acquisition in Clinical Trials for Radiation Therapy

Cancer treatment evolves through oncology clinical trials. Cancer trials are multimodal and complex. Assuring high-quality data are available to answer not only study objectives but also questions not anticipated at study initiation is the role of quality assurance. The National Cancer Institute reorganized its cancer clinical trials program in 2014. The National Clinical Trials Network (NCTN) was formed and within it was established a Diagnostic Imaging and Radiation Therapy Quality Assurance Organization. This organization is Imaging and Radiation Oncology Core, the Imaging and Radiation Oncology Core Group, consisting of 6 quality assurance centers that provide imaging and radiation therapy quality assurance for the NCTN. Sophisticated imaging is used for cancer diagnosis, treatment, and management as well as for image-driven technologies to plan and execute radiation treatment. Integration of imaging and radiation oncology data acquisition, review, management, and archive strategies are essential for trial compliance and future research. Lessons learned from previous trials are and provide evidence to support diagnostic imaging and radiation therapy data acquisition in NCTN trials.

The structure for a radiation oncology protocol

Abstract Multi-institutional Cooperative Group clinical trials involving radiotherapy require unambiguous therapeutic guidelines, so that patients entered from each of the participating institutions will receive essentially uniform treatment. The technical guidelines for a Radiation Oncology Protocol presented in this report represents a consensus of the Radiotherapy Committees in the major NCI funded Cooperative Groups and is derived from over a decade of expperience. Alhough they have been written for external beam therapy, theyare applicable to brachytherapy with appropriate technical considerations. It is anticipated that further evolution will occur with the introduction of new technologies such as 3-D treatment planning and delivery, multi-leaf collimation and small field irradiation.

Technical structure of a radiotherapy protocol

Multi-institutional cooperative group trials require conformity to a uniform set of therapeutic guidelines so that all patients entered on the study are treated the same regardless of which participating center enters the case. This can come about only if an unambiguous, clearly defined treatment program is included in the protocol. Examples of confusing protocol guidelines from recent Group studies demonstrate how well-meaning participants can inadvertently deviate from study requirements. The Quality Assurance Review Center has developed an outline for the radiotherapy component of a study which has alleviated this problem considerably.

WE‐G‐141‐01: The Imaging and Radiation Oncology Core (IROC) Group: A Proposed New Clinical Trial Quality Assurance Organization

PURPOSEnThe NCI is implementing the new National Clinical Trial Network (NCTN) Program in 2014 reducing the number of existing study groups from ten to five. The NCTN Program also requires a new combined Imaging and Radiation Oncology Core (IROC) service to provide a uniform QA program.nnnMETHODSnThe six existing clinical trial QA centers, Radiological Physics Center, Quality Assurance Review Center, RTOG QA Center, Image Guided Therapy Center, ACRIN Core Lab and the CALGB Imaging Core Lab have combined to form IROC. The interdependencies between diagnostic imaging and radiation therapy (RT) will be synergized in IROC eliminating duplication of services within the network and optimizing efficient and effective workflows. A major strength of this new organization will be the development of consistent standard operating procedures for all imaging and RT aspects of the NCTN as well as to facilitate a seamless flow of imaging and RT datasets across the network.nnnRESULTSnIROC, administered though the American College of Radiology will provide the scientific and technical expertise in both diagnostic imaging and RT to the entire NCTN Program capitalizing on existing infrastructure and expertise at QA centers currently providing services to the NCI Cooperative Groups. IROCs organizational structure will allow the delivery of a broad array of imaging and RT QA services including Site Qualification; Trial Design Support; Credentialing; Data Management and Case Review. IROC will work closely with the leadership of each Network Group and NCI to assure them that imaging and RT data used by the Groups for protocol analysis are accurate.nnnCONCLUSIONnThe proposed IROC Group has hundreds of collective years of experience conducting clinical trial QA and fully understands the QA needs/dataflow requirements of clinical trials to maintain the highest quality clinical trial data that will not obscure the outcomes of clinical trials. This work was supported by PHS grants CA10953, CA21661, CA029511 and CA081647 awarded by NCI, DHHS.