Faculty Bibliography

PURPOSE/OBJECTIVE:Previous studies indicate the benefit of therapy depends on patients' risk for cancer recurrence relative to non-cancer mortality (ω ratio). We sought to test the hypothesis that head and neck cancer (HNC) patients with a higher ω ratio selectively benefit from intensive therapy. EXPERIMENTAL DESIGN/METHODS:We analyzed 2688 patients with stage III-IVB HNC undergoing primary radiation therapy (RT) with or without systemic therapy on three phase III trials (RTOG 9003, RTOG 0129, and RTOG 0522). We used generalized competing event regression to stratify patients according to ω ratio, and compared the effectiveness of intensive therapy as a function of predicted ω ratio (i.e., ω score). Intensive therapy was defined as treatment on an experimental arm with altered fractionation (AFX) and/or multiagent concurrent systemic therapy. A nomogram was developed to predict patients' ω score based on tumor, demographic, and health factors. Analysis was by intention-to-treat. RESULTS:Decreasing age, improved performance status, higher body mass index, node positive status, P16 negative status, and oral cavity primary predicted a higher ω ratio. Patients with ω score ≥ 0.80 were more likely to benefit from intensive treatment (5-year OS, 70.0% vs. 56.6%; HR 0.73, 95% CI 0.57-0.94; P=0.016) than those with a ω score < 0.80 (5-year OS, 46.7% vs. 45.3%; HR 1.02, 95% CI 0.92-1.14; P=0.69;P=0.019 for interaction). In contrast, the effectiveness of intensive therapy did not depend on risk of progression. CONCLUSION/CONCLUSIONS:HNC patients with a higher ω score selectively benefit from intensive treatment. A nomogram was developed to help select patients for intensive therapy.

Background: Malnutrition incidence in cancer approaches 85%, disproportionately burdening those with lung, GI, and advanced stage cancers. Malnourished patients have impaired chemotherapy response, shorter survival, longer hospital stays, and decreased QoL. Home delivered meals are nutritional interventions that improve patient well- being, nutrition, and lower healthcare costs in the elderly but have not been studied as an intervention in cancer patients. HDMTM are nutritionist prescribed home delivered meals tailored to patient's symptoms, co-morbidities, and health needs. Preliminary data in 211 cancer patients showed with HDMTM 87% ate more than half of meals, 91% lived more independently, 89% ate more nutritiously, and 70% had less fatigue. HDMTM may be a strategy to reduce financial toxicity and healthcare utilization and improve QoL in cancer patients, but no primary data exists evaluating its efficacy.
Method(s): We sought to develop the first RCT evaluating patientcentered QoL improvement from nutritional intervention with HDMTM in those with metastatic lung and non-colorectal GI cancer. We established a partnership with God's Love We Deliver, a 501c3 non-profit specializing in HDMTM.
Result(s): We developed a protocol for a single-institution RCT of standard of care (SoC) versus SoC and HDMTM in metastatic lung and non-colorectal GI cancer patients with primary aim comparing QoL between arms at 12 weeks using the FACT-G questionnaire. Sample size is 180. Secondary aims assess HDMTM's impact on nutritional status, weight, mood, survival, food security, financial toxicity, healthcare utilization, and cost effectiveness. Eligible patients tolerate oral alimentation, have PS 0-3, and newly diagnosed (< 6 weeks) metastatic cancer. All patients have pre-randomization nutritional evaluation by an oncologic dietician.
Conclusion(s):We present the first PRMC reviewed and IRB approved RCT evaluating the efficacy of HDMTM in metastatic cancer patients with primary endpoint of patient reported QoL. Investigating HDMTM expands our knowledge of nutrition as an effective arm of palliative oncology

Objective: The Gynecologic Oncology Group (GOG) study 240 demonstrated a 3.5-month improvement in overall survival when bevacizumab (bev) was added to a combination chemotherapy regimen. This study established a bev-containing regimen as standard therapy for women with recurrent, persistent, or metastatic cervical cancer (CC). Gastrointestinal fistula (GIF) formation is a known complication of bev, and the long-term data of GOG 240 reported that a GIF rate of 15% in women who were treated with bev compared to 1% in the control group women. We sought to evaluate our experience with women treated with bev for CC and to identify associated risk factors for GIF formation.
Method(s): All patients who have received bev for CC from 2012 to 2018 at two academic institutions were identified, and their records were reviewed. Standard two-sided statistical analyses were performed.
Result(s): A total of 43 women were treated with a bev-containing chemotherapy regimen; among them, 34 (79.1%) were treated for CC recurrence, and the remaining were treated for metastatic disease at initial presentation or persistent disease following primary treatment. Thirty-three women (76.6%) received prior radiation therapy (RT); of these, 10 (32.3%) received external beam radiation therapy (EBRT), and 21 (67.7%) had prior EBRT and brachytherapy (BT). The median dose of bev was 15 mg/kg for both EBRT only and EBRT and BT groups. Eleven women developed GIF after bev treatment (11/43, 25.6%). All 11 (100%) had been previously treated with RT, and six (54.5%) had received EBRT plus BT. This resulted in rates of 33.3% (11/33) for GIF formation among women who received EBRT, and 28.6% (6/21) for GIF formation among women who received EBRT plus BT. The median number of bev cycles prior to GIF development was 8 (1-29), and 7 (7/11, 63.6%) received the dose of bev (15 mg/kg) as prescribed in GOG 240. See Table 1.
Conclusion(s): In our cohort of women with CC who were treated with bev, over 25% developed GIF. This is more than expected based on the 15% seen in GOG 240. Notably almost all who developed GIF had recurrent disease and were treated with prior RT. A third of women treated with RT followed by bev formed GIF, representing a considerable proportion of the cohort. GIF development and the possibility of requiring a colostomy should be a part of counseling prior to bev initiation especially in those who have had prior RT. [Figure presented]
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OBJECTIVE:Radiobiological models have been used to calculate the outcomes of treatment plans based on dose-volume relationship. This study examines several radiobiological models for the calculation of tumor control probability (TCP) of intensity modulated radiotherapy plans for the treatment of lung, prostate, and head and neck (H&N) cancers. METHODS:Dose volume histogram (DVH) data from the intensity modulated radiotherapy plans of 36 lung, 26 prostate, and 87  H&N cases were evaluated. The Poisson, Niemierko, and Marsden models were used to calculate the TCP of each disease group treatment plan. The calculated results were analyzed for correlation and discrepancy among the three models, as well as different treatment sites under study. RESULTS:The median value of calculated TCP in lung plans was 61.9% (34.1-76.5%), 59.5% (33.5-73.9%) and 32.5% (0.0-93.9%) with the Poisson, Niemierko, and Marsden models, respectively. The median value of calculated TCP in prostate plans was 85.1% (56.4-90.9%), 81.2% (56.1-88.7%) and 62.5% (28.2-75.9%) with the Poisson, Niemierko, and Marsden models, respectively. The median value of calculated TCP in H&N plans was 94.0% (44.0-97.8%) and 94.3% (0.0-97.8%) with the Poisson and Niemierko models, respectively. There were significant differences between the calculated TCPs with the Marsden model in comparison with either the Poisson or Niemierko model (p < 0.001) for both lung and prostate plans. The TCPs calculated by the Poisson and Niemierko models were significantly correlated for all three tumor sites. CONCLUSION/CONCLUSIONS:There are variations with different radiobiological models. Understanding of the correlation and limitation of a TCP model with dosimetric parameters can help develop the meaningful objective functions for plan optimization, which would lead to the implementation of outcome-based planning. More clinical data are needed to refine and consolidate the model for accuracy and robustness. Advances in knowledge: This study has tested three radiobiological models with varied disease sites. It is significant to compare different models with the same data set for better understanding of their clinical applicability.

We describe a case of the first successful treatment of platinum refractory clear cell ovarian cancer with secondary cytoreductive surgery and placement of Calypso transponders to facilitate post-operative volumetric arc radiation therapy. In the setting of both primary and recurrent disease, patients with clear cell ovarian cancer are less responsive to standard chemotherapy and those treated with radiation therapy may have improved outcomes compared to the use of other treatment modalities. Volumetric arc radiation therapy with implantable transponders is feasible, and allows for the targeted treatment of sites of metastatic disease while limiting toxicity to surrounding structures and can be considered for patients with recurrent ovarian cancer and oligometastatic disease.

Purpose/UNASSIGNED:While Ir-192 remains the mainstay isotope for gynecologic high-dose-rate (HDR) brachytherapy in the U.S., Co-60 is used abroad. Co-60 has a longer half-life than Ir-192, which may lead to long-term cost savings; however, its higher energy requires greater shielding. This study analyzes Co-60 acceptability based on a one-time expense of additional shielding and reports the financial experience of Co-60 in Peru's National Cancer Institute, which uses both isotopes. Material and methods/UNASSIGNED:A nationwide survey was undertaken assessing physician knowledge of Co-60 and willingness-to-pay (WTP) for additional shielding, assuming a source more cost-effective than Ir-192 was available. With 440 respondents, 280 clinicians were decision-makers and provided WTPs, with results previously reported. After completing a shielding report, we estimated costs for shielding expansion, noting acceptability to decision makers' WTP. Using activity-based costing, we note the Peruvian fiscal experience. Results/UNASSIGNED:Shielding estimates ranged from $173,000 to $418,000. The percentage of respondents accepting high-density modular or lead shielding (for union and non-union settings) were 17.5%, 11.4%, 3.9%, and 3.2%, respectively. Shielding acceptance was associated with greater number of radiation oncologists in a respondent's department but not time in practice or the American Brachytherapy Society membership. Peru's experience noted cost savings with Co-60 of $52,400 annually. Conclusions/UNASSIGNED:By comparing the cost of additional shielding for a sample institution's HDR suite with radiation oncologists' WTP, this multi-institutional collaboration noted < 20% of clinicians would accept additional shielding. Despite low acceptability in the US, Co-60 demonstrates cost-favorability in Peru and may similarly in other locations.