The Influence of Patient and System Factors on the Radiotherapy Treatment Time in the Treatment of Non-metastatic Cervical Cancer Patients in a Rural and Resource-Lean State's Safety-Net Hospital: Benefits of Strategic Planning.

Objective To decrease radiotherapy treatment time (RTT), measured from the day of initiation of radiotherapy to the day of its completion, specific strategies were initiated in early 2020 in the only academic safety-net medical center in a rural, resource-lean state. The factors that can succeed and those that need further improvements were analyzed in this initial assessment phase of our efforts to shorten the RTT. Methods This is an analysis of 28 cervix cancer patients treated with magnetic resonance imaging (MRI)-guided brachytherapy (February 2020-November 2021). The relationship between independent and dependent variable were analyzed by simple linear regression, and p-values ≤ 0.05 were considered statistically significant. SPSS software version 28.0 (IBM, Armonk, NY, USA) was used for statistical analysis. Results Two RTT groups (≤ 60 (32.1%) vs. > 60 days {67.9%}) with median RTT of 68 days (range, 51 to 106 days) were analyzed. Caucasians represented 66.7% of the RTT ≤ 60 days group. Four 'issues' were identified that increased the RTT: non-compliance, learning curve (early days of implementation of MRI-guided brachytherapy in the department), stage IV comorbidities, and with more than one issue mentioned; 77.8% with no issues had ≤ 60 days RTT vs. 26.3% for the > 60 days group. The breakdown of the no-issues factor by calendar year showed the RTT of ≤ 60 days was achieved higher in 2021 (85.7% vs. 20.0%; p=0.023) compared to 2020. For this entire cohort, the RTT of ≤ 60 days was achieved higher in 2021 (50.0% vs. 8.3%; p=0.019) compared to 2020. Data also showed improvement in RTT of ≤ 60 days for every sequential six months. 'Non-compliance' and 'learning curve' were the most important factors among patients having the longest RTTs. Conclusion The RTT can be further decreased. As a result of this preliminary analysis of the our strategic planning approach of 'circular' "See it," "Own it," "Solve it," and "Do it" and go back to the first step again, we plan to implement the following strategies in the immediate future to shorten the RTTs further and, in turn, improve our overall outcomes (local/regional control, disease-free survival, and overall survival): (a) Interdigitate MRI-guided brachytherapy during external beam radiotherapy (EBRT); patients who can not get the interdigitated brachytherapy procedures performed during the course of EBRT for any reason will receive two brachytherapy procedures per week; (c) attempt to add a cervix cancer care navigator to our staff to help patients having social issues, thus leading to compliance problems; (d) finally, in a year or two after these new strategic implementations, the RTT data will be reanalyzed.

Do We Need a New Approach to Cancer Biology Education for Radiation Oncology Residents?

Traditional radiation oncology biology courses largely focus on radiation biology and oncology as needed for passing the boards. Changes in the landscape of oncology necessitate a broader scope. Radiotherapy is an important component of cancer care. Approximately 70% of all cancer patients receive radiotherapy during the course of their disease. With the revolution in precision medicine that is unfolding, genomics, proteomics, metabolomics, and microbiomics are being ever more integrated into the treatment of cancer. Comprehensive knowledge of cancer biology beyond traditional radiation biology is essential for future advances in radiotherapy and unavoidable for radiation oncology trainees. The importance of a newly designed curriculum to impart broader knowledge to future radiation oncologists is emphasized in this report. A paradigm shift in the approach to the traditional radiation biology course is required to train residents for the future of oncology.

Use of Amifostine for Cytoprotection during Radiation Therapy: A Review.

BACKGROUND: Radiation therapy is a cornerstone of the therapeutic modalities used in modern oncology. However, it is sometimes limited in its ability to achieve optimal tumor control by radiation-induced normal tissue toxicity. In delivering radiation therapy, a balance must be achieved between maximizing the dose to the tumor and minimizing any injury to the normal tissues. Amifostine was the first Food and Drug Administration (FDA)-approved clinical radiation protector intended to reduce the impact of radiation on normal tissue, lessening its toxicity and potentially allowing for increased tumor dose/control. Despite being FDA-approved almost 20 years ago, Amifostine has yet to achieve widespread clinical use. SUMMARY: A thorough review of Amifostine's development, mechanism of action, and current clinical status were conducted. A brief history of Amifostine is given, from its development at Walter Reid Institute of Research to its approval for clinical use. The mechanism of action of Amifostine is explored. The results of a complete literature review of all prospective randomized trials to date involving the use of Amifostine in radiation therapy are presented. The results are arranged by treatment site and salient findings discussed. Side effects and complications to consider in using Amifostine are reviewed. Key Messages: Amifostine has been explored as a radiation protectant in most radiation treatment sites. Studies have demonstrated efficacy of Amifostine in all treatment sites reviewed, but results are heterogeneous. The heterogeneity of studies looking at Amifostine as a clinical radiation protectant has precluded a definitive answer on its efficacy. Complicating its clinical use is its toxicity and delivery requirements. Amifostine has largely fallen out of use with the advent of intensity modulated radiation therapy (IMRT). However, side effects with IMRT remain a challenge and concern. The use of Amifostine in the IMRT era has been poorly explored and is worthy of future study.

A Case of Transformation of Primary Cutaneous Follicle Center Lymphoma to Diffuse Large B-Cell Lymphoma Involving the Parotid Gland and Cervical Lymph Nodes.

BACKGROUND Transformation of primary cutaneous follicle center lymphoma (PCFCL), a low-grade B-cell non-Hodgkin lymphoma (NHL), into a high-grade NHL is rare with uncertain prognosis and treatment. A case is reported of a 40-year-old man who presented with a scalp mass that was diagnosed histologically as PCFCL. Imaging of the head and neck identified diffuse large B-cell lymphoma (DLBCL) involving the parotid gland and cervical lymph nodes, which responded well to radiation therapy. CASE REPORT A 40-year-old African American man presented with a two-year history of a progressively enlarging scalp mass that measured 10.5×7.1×6.6 cm. Histology showed a low-grade lymphoma with a follicular pattern. Immunohistochemistry was positive for B-cell markers and Bcl-6, consistent with a diagnosis of PCFCL. Computed tomography (CT) identified a 4.9×3.7×3.4 cm mass in the left parotid gland with bilateral cervical lymphadenopathy that had been present for the previous two or three months. The diagnosis of DLBCL was made on histology from a needle biopsy. Treatment began with rituximab, etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (R-EPOCH) chemotherapy, followed by radiation therapy to the scalp, both sides of the neck, and left parotid gland. At four-month follow-up, combined positron emission tomography (PET) and CT showed only diffuse low-level uptake in the scalp and parotid gland. CONCLUSIONS Transformation of low-grade PCFCL to high-grade DLBCL is rare, and the approach to treatment varies. This case showed a good response to chemotherapy and radiation therapy.

Thoracic radiation-induced pleural effusion and risk factors in patients with lung cancer.

The risk factors and potential practice implications of radiation-induced pleural effusion (RIPE) are undefined. This study examined lung cancer patients treated with thoracic radiation therapy (TRT) having follow-up computed tomography (CT) or 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT. Increased volumes of pleural effusion after TRT without evidence of tumor progression was considered RIPE. Parameters of lung dose-volume histogram including percent volumes irradiated with 5-55 Gy (V5-V55) and mean lung dose (MLD) were analyzed by receiver operating characteristic analysis. Clinical and treatment-related risk factors were detected by univariate and multivariate analyses. 175 out of 806 patients receiving TRT with post-treatment imaging were included. 51 patients (24.9%) developed RIPE; 40 had symptomatic RIPE including chest pain (47.1%), cough (23.5%) and dyspnea (35.3%). Female (OR = 0.380, 95% CI: 0.156-0.926, p = 0.033) and Caucasian race (OR = 3.519, 95% CI: 1.327-9.336, p = 0.011) were significantly associated with lower risk of RIPE. Stage and concurrent chemotherapy had borderline significance (OR = 1.665, p = 0.069 and OR = 2.580, p = 0.080, respectively) for RIPE. Patients with RIPE had significantly higher whole lung V5-V40, V50 and MLD. V5 remained as a significant predictive factor for RIPE and symptomatic RIPE (p = 0.007 and 0.022) after adjusting for race, gender and histology. To include, the incidence of RIPE is notable. Whole lung V5 appeared to be the most significant independent risk factor for symptomatic RIPE.

DNA Damage Response Proteins and Oxygen Modulate Prostaglandin E2 Growth Factor Release in Response to Low and High LET Ionizing Radiation.

Common cancer therapies employ chemicals or radiation that damage DNA. Cancer and normal cells respond to DNA damage by activating complex networks of DNA damage sensor, signal transducer, and effector proteins that arrest cell cycle progression, and repair damaged DNA. If damage is severe enough, the DNA damage response (DDR) triggers programed cell death by apoptosis or other pathways. Caspase 3 is a protease that is activated upon damage and triggers apoptosis, and production of prostaglandin E2 (PGE2), a potent growth factor that can enhance growth of surviving cancer cells leading to accelerated tumor repopulation. Thus, dying tumor cells can promote growth of surviving tumor cells, a pathway aptly named Phoenix Rising. In the present study, we surveyed Phoenix Rising responses in a variety of normal and established cancer cell lines, and in cancer cell lines freshly derived from patients. We demonstrate that IR induces a Phoenix Rising response in many, but not all cell lines, and that PGE2 production generally correlates with enhanced growth of cells that survive irradiation, and of unirradiated cells co-cultured with irradiated cells. We show that PGE2 production is stimulated by low and high LET ionizing radiation, and can be enhanced or suppressed by inhibitors of key DDR proteins. PGE2 is produced downstream of caspase 3 and the cyclooxygenases COX1 and COX2, and we show that the pan COX1-2 inhibitor indomethacin blocks IR-induced PGE2 production in the presence or absence of DDR inhibitors. COX1-2 require oxygen for catalytic activity, and we further show that PGE2 production is markedly suppressed in cells cultured under low (1%) oxygen concentration. Thus, Phoenix Rising is most likely to cause repopulation of tumors with relatively high oxygen, but not in hypoxic tumors. This survey lays a foundation for future studies to further define tumor responses to radiation and inhibitors of the DDR and Phoenix Rising to enhance the efficacy of radiotherapy with the ultimate goal of precision medicine informed by deep understanding of specific tumor responses to radiation and adjunct chemotherapy targeting key factors in the DDR and Phoenix Rising pathways.

Accuracy and precision of cone-beam computed tomography guided intensity modulated radiation therapy.

PURPOSE: To assess the accuracy and precision of cone-beam computed tomography (CBCT)-guided intensity modulated radiation therapy (IMRT). METHODS AND MATERIALS: A 7-field intensity modulated radiation therapy plan was constructed for an anthropomorphic head phantom loaded with a custom cassette containing radiochromic film. The phantom was positioned on the treatment table at 9 locations: 1 "correct" position and 8 "misaligned" positions along 3 orthogonal axes. A commercial kilovoltage cone-beam computed tomography (kV-CBCT) system (VolumeView, Elekta AB, Stockholm, Sweden) was then used to align the phantom prior to plan delivery. The treatment plan was delivered using the radiation therapy delivery system (Infinity; Elekta AB) 3 times for each of the 9 positions, allowing film measurement of the delivered dose distribution in 3 orthogonal planes. Comparison of the planned and delivered dose profiles along the major axes provided an estimate of the accuracy and precision of CBCT-guided IMRT. RESULTS: On average, targeting accuracy was found to be within 1 mm in all 3 major anatomic planes. Over all 54 measured dose profiles, the means and standard errors of the displacement of the center of the field between the measured and calculated profiles for each of the right-left, anterior-posterior, and superior-inferior axes were +0.08 ± 0.07 mm, +0.60 ± 0.08 mm, and +0.78 ± 0.16 mm, respectively. Agreement between planned and measured 80% profiles was less than 0.4 mm on either side along the right-left axis. A systematic shift of the measured profile of slightly less than 1 mm in anterior and superior directions was noted along the anterior-posterior and superior-inferior axes, respectively. CONCLUSIONS: Submillimeter targeting accuracy can be achieved using a commercial kV-CBCT IGRT system.