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Literature supporting the efficacy of complementary and integrative medicine (CIM) alongside radiotherapy is fragmented with varying outcomes and levels of evidence. This review summarizes the available evidence on CIM used with radiotherapy in order to inform clinicians. A systematic literature review identified studies on the use of CIM during radiotherapy. Inclusion required the following criteria: the study was interventional, CIM therapy was for human patients with cancer, and CIM therapy was administered concurrently with radiotherapy. Data points of interest were collected from included studies. A subset was identified as high-quality using the Jadad scale. Fisher’s exact test was used to assess the association between study results, outcome measured, and type of CIM. Overall, 163 articles met inclusion. Of these, 68 (41.7%) were considered high-quality trials. Articles published per year increased over time (p < 0.01). Frequently identified therapies were biologically based therapies (47.9%), mind-body therapies (23.3%), and alternative medical systems (13.5%). Within the subset of high-quality trials, 60.0% of studies reported a favorable change with CIM while 40.0% reported no change. No studies reported an unfavorable change. Commonly assessed outcome types were patient-reported (41.1%) and provider-reported (21.5%). Rate of favorable change did not differ based on type of CIM (p = 0.90) or outcome measured (p = 0.24). Concurrent CIM may reduce radiotherapy-induced toxicities and improve quality of life, suggesting that physicians should discuss CIM with patients receiving radiotherapy. This review provides a broad overview of investigations on CIM use during radiotherapy and can inform how radiation oncologists advise their patients about CIM.

PURPOSE: This study assessed the safety and tolerability of therapeutic immunization against the human papillomavirus (HPV) viral oncoproteins E6 and E7 in patients with cervical cancer after chemoradiation. METHODS AND MATERIALS: MEDI0457 (INO-3112) is a DNA-based vaccine targeting E6 and E7 of HPV-16/18 that is coinjected with an IL-12 plasmid followed by electroporation with the CELLECTRA 5P device. At 2 to 4 weeks after chemoradiation, patients with newly diagnosed stage IB1-IVA (cohort 1) or persistent/recurrent (cohort 2) cervical cancers were treated with 4 immunizations of MEDI0457 every 4 weeks. The primary endpoints were incidence of adverse events and injection site reactions. Immune responses against HPV antigens were measured by ELISpot for interferon-γ (IFNγ), enzyme-linked immunosorbent assay for antibody responses and multiplexed immunofluorescence for immune cells in cervical biopsy specimens. RESULTS: Ten patients (cohort 1, n = 7; cohort 2, n = 3) with HPV16 (n = 7) or HPV18 (n = 3) cervical cancers received MEDI0457 after chemoradiation. Treatment-related adverse events were all grade 1, primarily related to the injection site. Eight of 10 patients had detectable cellular or humoral immune responses against HPV antigens after chemoradiation and vaccination: 6 of 10 patients generated anti-HPV antibody responses and 6 of 10 patients generated IFNγ-producing T cell responses. At the completion of chemoradiation and vaccination, cervical biopsy specimens had detectable CD8(+) T cells and decreased PD-1(+)CD8(+), PD-L1(+)CD8(+), and PD-L1(+)CD68(+) subpopulations. All patients cleared detectable HPV DNA in cervical biopsies by completion of chemoradiation and vaccination. CONCLUSIONS: Adjuvant MEDI0457 is safe and well tolerated after chemoradiation for locally advanced or recurrent cervical cancers, supporting further investigation into combining tumor-specific vaccines with radiation therapy.

Purpose: Patients with cervical cancer are at high risk for opioid use. This study aimed to characterize opioid prescribing patterns at 2 urban hospitals. Methods and Materials: Data from patients with cervical cancer treated with curative intent from 2011 to 2018 were retrospectively collected. Women with unrelated chronic opioid use before diagnosis, persistent/recurrent disease at 3 months after initiation of treatment, or initiation of opioids >6 months after treatment were excluded. Demographics, disease characteristics, treatment, and outpatient prescription practices were collected. Endpoints included duration of opioid use ≥6 and ≥12 months. Results: There were 106 women included, of whom 83% received definitive radiation. Most patients (n = 91, 85.8%) received outpatient opioids. Most common timing of prescriptions were before cancer therapy (35.9%), postprocedure (26.4%), and during radiation therapy (17.0%). Median duration was 3 (interquartile range, 1-11) months; 35.2% of these patients received opioids ≥6 months and 22% received opioids ≥12 months. Greater International Federation of Gynaecology and Obstetrics (FIGO) stage, recurrent/residual disease, initiation of opioids before treatment, history of depression or anxiety, and use of gabapentin or steroids were associated with long-term opioid use. Conclusions: Most patients were prescribed outpatient opioids, many of whom used opioids for 12 months. Improvement in provider communication and education, increased posttreatment monitoring, and further evaluation of nonopioid therapies are needed in this patient population to reduce long-term opioid use.

OBJECTIVE Historically, external beam parametrial boost (EBPB) has been used in locally advanced cervical cancers to supplement radiation dose. However, it has become controversial in the era of image-guided brachytherapy. Modern 3D imaging and brachytherapy techniques have improved delineation and coverage of tumor. Outcomes with and without parametrial boost were analyzed. METHODS Women with cervical cancer involving the parametria (clinically or radiographically) diagnosed between 2001 and 2017 were identified. Clinicopathologic and treatment features, survival and patterns of failure data were collected. Univariate and multivariable data analysis was performed to evaluate association of these variables, including parametrial boost, with local failure-free survival and overall survival. Competing risks analysis was performed for cumulative incidence of local failure, with death and other failures treated as competing events. RESULTS A total of 100 women were identified (median follow-up 26.8 mo). Forty-one (41%) received EBPB; these patients were less likely to have received magnetic resonance imaging, positron emission tomography, interstitial, or high-dose rate brachytherapy. Magnetic resonance imaging, positron emission tomography, dose rate, and treatment era were highly correlated (Cramer's V: 0.43 to 0.68, P

Background: Recent studies incorporating dose escalated radiation identified heart dose as a predictor of cardiac toxicity in unresectable lung cancer patients. Whether conventionally dosed radiation impacts cardiac events remains unclear. Methods: Stage III lung cancer patients undergoing definitive chemoradiation to 60–70 Gy were analyzed. Clinical and dosimetric factors (mean heart dose, heart V5-60 in 5 Gy increments) were analyzed against freedom from ≥ grade 3 cardiac events and overall survival (OS) by log-rank test. Multivariable analysis (MVA) for factors significant on univariate analysis was performed by Cox proportional hazards. Results: A total of 108 patients were identified. Median follow-up was 18.0 months. One- and two-year OS were 79% and 61%, respectively. On MVA, gross tumor volume (GTV) ≥98.6 cm 3 [hazard ratio (HR): 2.11, 95% confidence interval (CI): 1.15–3.93, P=0.02] and female gender (HR: 2.01, 95% CI: 1.09–3.73, P=0.03) predicted for worse survival. Twelve patients (11%) developed ≥ grade 3 cardiac events. One- and two-year freedom from cardiac events (FFCE) was 94% and 84% respectively. On MVA, heart V5 ≥49% predicted for cardiac events (HR: 11.44, 95% CI: 1.31–111.60, P=0.03) while female gender was nearly significant (HR: 3.49, 95% CI: 0.97–16.80, P=0.06). Females presented with similar comorbidity scores, GTVs, and relapse rates but experienced higher heart doses than their male counterparts. Conclusions: Heart V5 ≥49% predicted for cardiac events after chemoradiation. However, cardiac dosimetry was not associated with survival. Rather, female gender and GTV ≥98.6 cm 3 led to worse survival. This study corroborates emerging data that low-dose radiation to the heart impacts cardiac toxicity.

Tumor-induced CD45(−)Ter119(+)CD71(+) erythroid progenitor cells (EPCs), termed “Ter-cells,” promote tumor progression by secreting artemin, a neurotrophic peptide that activates REarranged during Transfection (RET) signaling. We demonstrate that both local tumor ionizing radiation (IR) and anti-Programmed death ligand 1 (PD-L1) treatment decreased tumor-induced Ter-cell abundance in mouse spleen and artemin secretion outside the irradiation field in an interferon- (IFN) and CD8(+) T cell-dependent manner. Recombinant erythropoietin (EPO) promoted resistance to radiotherapy or anti-PD-L1 therapies by restoring Ter-cell numbers and serum artemin concentration. Blockade of artemin or potential artemin signaling partners, or depletion of Ter-cells augmented the anti-tumor effects of both IR and anti-PD-L1 therapies in mice. Analysis of samples from patients who received radio-immunotherapy demonstrated that IR-mediated reduction of Ter-cells, artemin, and GFRα3, an artemin signaling partner, were each associated with tumor regression. Patients with melanoma who received immunotherapy exhibited favorable outcomes associated with decreased expression of GFRα3. These findings demonstrate an out-of-field, or “abscopal,” effect mediated by adaptive immunity, which is induced during local tumor irradiation. This effect, in turn, governs the therapeutic effects of radiation and immunotherapy. Therefore, our results identify multiple targets to potentially improve outcomes following radiotherapy and immunotherapy.

Literature supporting the efficacy of complementary and integrative medicine (CIM) alongside radiotherapy is fragmented with varying outcomes and levels of evidence. This review summarizes the available evidence on CIM used with radiotherapy in order to inform clinicians.A systematic literature review identified studies on the use of CIM during radiotherapy. Inclusion required the following criteria: the study was interventional, CIM therapy was for human patients with cancer, and CIM therapy was administered concurrently with radiotherapy. Data points of interest were collected from included studies. A subset was identified as high-quality using the Jadad scale. Fisher's exact test was used to assess the association between study results, outcome measured, and type of CIM.Overall, 163 articles met inclusion. Of these, 68 (41.7%) were considered high-quality trials. Articles published per year increased over time (p0.01). Frequently identified therapies were biologically based therapies (47.9%), mind-body therapies (23.3%), and alternative medical systems (13.5%). Within the subset of high-quality trials, 60.0% of studies reported a favorable change with CIM while 40.0% reported no change. No studies reported an unfavorable change. Commonly assessed outcome types were patient-reported (41.1%) and provider-reported (21.5%). Rate of favorable change did not differ based on type of CIM (p = 0.90) or outcome measured (p = 0.24).Concurrent CIM may reduce radiotherapy-induced toxicities and improve quality of life, suggesting that physicians should discuss CIM with patients receiving radiotherapy. This review provides a broad overview of investigations on CIM use during radiotherapy and can inform how radiation oncologists advise their patients about CIM.

Purpose: Radiotherapy patient education materials fail to meet readability standards, impairing access for patients with low educational attainment, disabilities, or limited-English proficiency. Design professionals and physicians developed graphic narrative discussion guides, Communication of the Gynecologic Brachytherapy Experience (CoGBE), for cylinder, intracavitary, and interstitial high-dose rate (HDR) gynecologic brachytherapy. This study assesses perceived clinical benefits, usability, and anxiety-reduction of CoGBE. Methods: An electronic survey was sent to members of the American Brachytherapy Society. Participants were assigned to assess one of the three modality-specific CoGBE guides using a modified Systems Usability Scale (mSUS), modified state-trait anxiety index (mSTAI), and Likert-type questions. Free response data was analyzed using modified grounded theory. Results: Median mSUS score was 76.3 (interquartile range [IQR], 71.3-82.5) and there were no significant differences between guide types. Median mSTAI was 40 (IQR, 40-43.3) for all guides collectively. The cylinder guide had a significantly higher median mSTAI than the intracavitary and interstitial guides (41.6 vs 40.0 and 40.0; p=0.04) suggesting the cylinder guide may have less impact on reducing anxiety. 72.7% rated CoGBE as “quite” or “extremely” helpful compared to a text-only pamphlet. When compared to their current education practices, 77.3% reported patients would understand “more” or “a lot more” after initial consultation and 81.8% reported CoGBE would be at least moderately helpful in making initial consultations more memorable for patients. Lastly, 79.5% reported at least a moderate likelihood of using CoGBE. Qualitative analysis themes included personalization, relatability, and graphic narrative (positive domains); generalizability and character affect (negative domains). Conclusion: Clinicians rate CoGBE as usable with potential to reduce patient anxiety, especially with more invasive treatment modalities including intracavitary or interstitial HDR. The CoGBE guides (including multilingual versions) have global applicability, in low resource settings with high cervical cancer burdens and patient populations that may benefit from the graphic narrative format. Citation Format: Santiago Avila, María J. Ruiz, Ritu Arya, Brian Callender, Yasmin Hasan, Josephine S. Kim, Nita Lee, Anne McCall, Christina H. Son, Kate Stack, Sabah Asif, Tyler Besecker, Arushi Juneja, Zhongyang Li, Pinakee Naik, Tanvi Ranka, Prachi Saxena, Brian Siegfried, Tomoko Ichikawa, Daniel W. Golden. Communicating the Gynecologic Brachytherapy Experience (CoGBE): Clinician Perceived Benefits of a Graphic Narrative Patient Education Tool [abstract]. In: Proceedings of the 9th Annual Symposium on Global Cancer Research; Global Cancer Research and Control: Looking Back and Charting a Path Forward; 2021 Mar 10-11. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2021;30(7 Suppl):Abstract nr 105.

Purpose The purpose of this study was to prospectively evaluate the use of daily 2-mm bolus in patients undergoing postmastectomy radiation without reconstruction using optically stimulated luminescence dosimetry and weekly assessment of skin toxicity. Methods and materials We prospectively collected data from the first 49 women treated with a daily 2-mm Superflab bolus during their postmastectomy radiation therapy from 2013 to 2016 at The University of Chicago Comprehensive Cancer Center at Silver Cross. Within the first 3 days of starting radiation therapy, we measured the surface dose in vivo at 5 anatomical locations under the 2-mm bolus on the chest wall. We assessed weekly the acute skin toxicity during radiation using the National Cancer Institute Common Toxicity Criteria. Patients with reconstruction before radiation therapy were excluded. Results Forty-nine women with a mean age of 54.3 years were treated with daily 2-mm bolus to the chest wall following mastectomy. Median follow-up was 32.7 weeks. The mean percentages of prescribed dose (standard deviation) for the median, central, lateral, superior, and inferior optically stimulated luminescence dosimeters were 100.1% (5.6%), 108.1% (6.7%), 98.1% (6.5%), 102.6% (8.9%), and 106.3% (6.6%), respectively. The majority (71.4%) of women experienced a maximum acute National Cancer Institute Common Toxicity Criteria skin toxicity score of 2, with only 12.2% experiencing a score of 3. There were no grade 4 toxicities. There were no local recurrences during our follow-up period. Conclusions A daily 2-mm bolus is a feasible regimen for chest wall bolus during postmastectomy radiation therapy with acceptable dose buildup and skin toxicity.

Importance Appropriate informed consent processes are crucial to preservation of patient autonomy and shared decision making. Although half of patients with cancer receive radiotherapy, it is unknown whether current consent practices are comprehensible for patients. Objective To characterize use, specificity, and readability of clinical informed consent forms for radiotherapy, hypothesizing that forms would be higher than the recommended sixth- to eighth-grade readability level. Design, Setting, and Participants This nationwide cross-sectional survey study and readability analysis was conducted from 2016 to 2018 and included 89 academic radiation oncology departments that were part of the 2016 Electronic Residency Application Service. Department leaders (clinical directors, chairs, and personal contacts of study authors) at academic radiation oncology departments were contacted via email. Main Outcomes and Measures Readability levels were measured by 7 validated readability indices, including the Ford, Caylor, Sticht (FORCAST) index for nonnarrative texts. Difficult words were identified usingThe Living Word Vocabulary, which describes the readability grade levels of 40 000 common words. Results Of 89 departments, 67 (75%) responded to questions and 57 (64%) provided 113 forms for analysis. Departments providing forms did not differ substantially from others in terms of region, residency size, research output, rural vs urban location, or public vs private institution status. All departments obtained patient written informed consent before radiotherapy; 38 (57%) used body site–specific forms. Using the most conservative (low-score) estimate, mean form readability ranged from grade level 10.6 to 14.2. By 7 distinct indices, only 9 (8%) of 113 forms met the recommended eighth-grade readability level, and 4 (4%) forms met a sixth-grade level. Not a single form met either recommendation based on the FORCAST index. Forms used an average of 7.2 difficult words. Body site–specific forms had considerably better readability than general consent forms. Conclusions and Relevance This nationwide study of informed consent practices for cancer treatment with radiotherapy demonstrates that while all US academic radiotherapy departments use written consent forms, it is rare for templates to meet the recommended readability levels for patient materials. These data suggest the need for reevaluation and modification of the approach to radiotherapy consent, ideally with guidance and templates designed by national professional organizations.

5525Background: DNA immunotherapies targeting HPV oncogenes, E6 and E7, have demonstrated clinical efficacy in pre-invasive cervical lesions. Here, we assessed the feasibility of chemoradiation and...

e22152Background: Given the importance of informed consent in cancer care, we sought to characterize readability and specificity of consent forms for radiation therapy, hypothesizing that readabili...

Two human squamous cell cervical carcinoma cell lines, C-33A (HTB 31) and MS751 (HTB 34), were exposed to either paclitaxel alone or paclitaxel for 24 hr followed by graded doses of Cs-137 radiation. Each was then analyzed for both clonogenic survival and alterations to cell cycle progression. No radiosensitization or affect on the cell cycle was seen using 1 × 10 −9 M paclitaxel. Each line was equally sensitive to the drug with approximately 50% cell lethality seen after 1 × 10 −8 M of paclitaxel. This concentration of paclitaxel also produced substantial G 2 M arrest, seen immediately after drug exposure and lasting up to 2 days. Gamma radiation delivered during the time of G 2 M arrest showed only a small degree of radiosensitization by paclitaxel for the relatively radioresistant MS751 line at 4 Gy (SF 4 = 16.0 ± 3.2% → 5.7 ± 1.1%, P = 0.049) but no sensitization using radiation doses of conventional fraction size [sensitizer enhancement ratios 1.1 (0.80–1.40) and 1.3 (0.95–1.65) for the C-33A and MS751 cell lines, respectively]. It is concluded that paclitaxel produces only a modest radiosensitization effect, indicating that this compound will have limited benefit as a radiosensitizer for the treatment of cervical cancer.

DNA analysis by flow cytometry has been reported to be a useful prognostic technique for a variety of malignant tumors. The goal of this study was to examine DNA ploidy status and proliferation index as potential predictors of recurrence and survival for patients with squamous cell vulvar carcinomas. The DNA ploidy, percentage of cells in the S-phase of the cell cycle, stage, and histologic grade were analyzed in 42 patients. Flow cytometry was performed on archival paraffin-embedded tissue. The histologic specimens were reviewed by a single pathologist. Thirty-four tumors (81%) were diploid and eight (19%) demonstrated an aneuploid peak. The percentage of cells in the S-phase (proliferation index) was calculated for all patients. The 5-year survival rate was 68% for diploid tumors and was 75% for aneuploid tumors. The difference between these rates was not statistically significant (P < or = 0.65). S-phase fraction was also not a useful predictor for recurrence or overall survival. FIGO stage and histologic grade were accurate predictors for both recurrence and 5-year survival. Multiple predictor analysis using stage, grade, ploidy status, and proliferation index did not identify any subgroup which would predict recurrence better than FIGO stage and grade. DNA ploidy and S-phase fraction analysis do not appear to be clinically useful prognostic factors for vulvar squamous cell carcinomas.

Background. The Gynecologic Oncology Group (GOG) protocol #88 reported an 18.5% failure in inguinal lymph nodes of patients with vulvar cancer whose groins were treated with radiation alone. This high failure rate may be due to the study design. Methods. In this study, the depths of inguinal lymph nodes were evaluated with computed tomography (CT) scans in 100 adult women without inguinal adenopathy or prior inguinal surgery. The dose that would have been delivered to the inguinal lymph nodes of these patients was determined using isodose curves constructed according to the guidelines in GOG protocol #88. Results. Only 18% of women had all inguinal lymph nodes measured at a depth of 3 cm or less. Conclusions. More than one-half of all women in this study would have received less than 60% of the prescribed radiation dose because their inguinal lymph nodes were deeper than 5 cm, if the depth of their inguinal lymph nodes had not been measured before therapy.

Purpose: A thorough dose–volume analysis of a standard tangential radiation technique has not been published. We evaluated the adequacy of a tangential radiation technique in delivering dose to the breast and regional lymphatics, as well as dose delivered to underlying critical structures. Methods and Materials: Treatment plans of 25 consecutive women with breast cancer undergoing lumpectomy and adjuvant breast radiotherapy were studied. Patients underwent two-dimensional (2D) treatment planning followed by treatment with standard breast tangents. These 2D plans were reconstructed without modification on our three-dimensional treatment planning system and analyzed with regard to dose–volume parameters. Results: Adequate coverage of the breast (defined as 95% of the target receiving at least 95% of the prescribed dose) was achieved in 16 of 25 patients, with all patients having at least 85% of the breast volume treated to 95% of the prescribed dose. Only 1 patient (4%) had adequate coverage of the Level I axilla, and no patient had adequate coverage of the Level II axilla, Level III axilla, or the internal mammary lymph nodes. Conclusion: Three-dimensional treatment planning is superior in quantification of the dose received by the breast, regional lymphatics, and critical structures. The standard breast tangent technique delivers an adequate dose to the breast but does not therapeutically treat the regional lymph nodes in the majority of patients. If coverage of the axilla or internal mammary lymph nodes is desired, alternate beam arrangements or treatment fields will be necessary.

Peripheral blood lymphocytes (PBLs) of patients with cervical intraepithelial neoplasia (CIN), cervical carcinoma, or early breast carcinoma were tested for the expression of T cell receptor zeta chain (TCR zeta) and CD16 zeta chain and production of interferon-gamma (IFN gamma) and interleukin (IL) 10. We found that in all patients with CIN and invasive cervical carcinoma, PBLs showed a reduced TCR zeta and CD16 zeta expression and a significant down-regulation in IFN gamma production (a T helper 1 cytokine) after anti-CD3 stimulation. However, the IL 10 secretion (a T helper 2 cytokine) was not diminished after anti-CD3 stimulation. This indicates that only T helper 1 cells are affected by the down-regulation of the TCR zeta chain expression. We also analyzed PBLs of 12 patients with early breast carcinoma. In these patients, we found TCR zeta and CD16 zeta expression down-regulation in 2 of 12 patients. Six of 12 patients had an enhanced TCR zeta expression. The enhanced TCR zeta expression correlated with a reduced IFN gamma expression after anti-CD3 stimulation. These data show that in general PBLs of early breast carcinoma patients, unlike those of cervical carcinoma patients, do not show a decreased TCR zeta expression. However, a functional impairment of T cells was observed in the subgroup of early breast carcinoma patients with a high nuclear grade of their tumor.

PURPOSE To determine the toxicity and prognosis of patients with relapsed and refractory diffuse aggressive non-Hodgkin's lymphoma (NHL) who underwent an autologous bone marrow transplant (ABMT) using augmented preparative regimens, treated in a major cooperative group setting, and to examine prognostic factors for outcome. PATIENTS AND METHODS Ninety-four patients with either chemosensitive (50 patients) or chemoresistant (44 patients) relapse, including 22 who failed induction chemotherapy, were treated with high-dose cyclophosphamide and etoposide with total-body irradiation (TBI) (67 patients) or an augmented carmustine (BCNU), cyclophosphamide, and etoposide (BCV) preparative regimen (27 patients) and an ABMT at 16 Southwest Oncology Group (SWOG) transplant centers. All relapsing patients were required to undergo a minimum of two courses of salvage therapy to determine chemosensitivity before transplant. Overall (OS) and progression-free survival (PFS) were determined and a Cox regression model was used to assess potential prognostic variables. RESULTS Of the 94 eligible patients, there were 10 (10.6%) deaths before day 50 posttransplant because of infection (six deaths), hemorrhagic alveolitis (three deaths), or bleeding (one death). The median 3-year PFS and OS for the entire group was 33% and 44%. For those with chemosensitive disease the PFS and OS were 42% and 55%, whereas for those with chemoresistant disease the PFS and OS were 22% and 29%. The PFS and OS for those failing induction chemotherapy were 27% and 32%. The relapse rates within the first 3 years for the chemosensitive relapse, chemoresistant, and induction failure groups were 61%, 40%, and 59%, respectively. For both PFS and OS, only disease status at transplant was a significant factor in the multivariate Cox model. CONCLUSION These results single institutional pilot trials exploring augmented preparative regimens. Patients undergoing transplantation for resistant disease, particularly those failing induction chemotherapy, appear to have an improved prognosis as compared with reports using standard preparative regimens. Therapies other than manipulation of standard preparative regimens appear to be required to decrease relapses following autotransplantation.

Materials and Methods: The two human ceil lines C-33A (HTB 31) and MS751 (HTB 34) were exposed to 1 x10”’ M to 1 x IO” M Pactitaxel for 24 hours. At this time the drug was washed off the cells and sample exposed to graded doses of Cs-137 radiation from O-4 Gy. These samples were then incubated for approximately 7-10 days to allOW colony formation, Separate samples were also followed for at least 6 days with daily sampling for cell cycle analysis.

Several single-institution pilot studies have suggested that augmented preparative regimens, including those containing total body irradiation combined with an autologous bone marrow transplantation, are superior to standard regimens for the treatment of relapsed or refractory Hodgkin disease. On the basis of these data, we undertook, in the cooperative group setting, a phase II trial of augmented preparative regimens for patients experiencing treatment failure with conventional chemotherapy. Eighty-one patients with either sensitive or refractory (induction failures or chemoresistant) relapse received etoposide (60 mg/kg), cyclophosphamide (100 mg/kg), and either total body irradiation (12 Gy) or, if previously irradiated, carmustine (15 mg/kg), followed by an autologous bone marrow transplantation. Progression-free (PFS) and overall (OS) survival were estimated, and a Cox regression model was used to assess potential prognostic variables. The 5-year PFS and OS for the 74 eligible patients treated at 20 Southwest Oncology Group centers were 41% (95% confidence interval [CI], 29%–53%) and 54% (95% CI, 43%–65%), respectively, despite a median remission after initial chemotherapy of only 6 months. The 3-year OS for those whose induction therapy failed was 72% (95% CI, 52%–93%). There was 1 (1.4%) early treatment-related death, 2 late deaths due to lung toxicity, and only 1 death due to myelodysplasia. There were no differences in PFS or OS on the basis of regimen or chemosensitivity. A Cox prognostic factor analysis determined that >2 prior regimens, relapse in a radiated field, and extranodal disease were adverse prognostic factors. Among the 46 patients who received prior radiotherapy, the 5-year OS was 38% (95% CI, 14%–61%) for patients with 2 or 3 adverse factors, versus 60% (95% CI, 42%–78%) for those with 0 factors or 1 adverse factor. Augmented preparative regimens seem promising for the treatment of relapsed or refractory Hodgkin disease, without an increase in regimen-related mortality. A poor-prognosis group was identified that should be treated with novel therapies.