Stage Migration in Cervical Cancer Using the FIGO 2018 Staging System: A Retrospective Survival Analysis Using a Single-Institution Patient Cohort.

Introduction The International Federation of Gynecology and Obstetrics (FIGO) changed the staging system for cervical cancer in 2018 and formally allowed cross-sectional imaging for staging purposes. Stage IB is now divided into three substages based on tumor size (IB1 < 2 cm, IB2 2-4 cm and IB3 > 4 cm). The presence of lymph nodes in the pelvis or para-aortic region will upstage the patient to stage IIIC. The purpose of this study was to evaluate the extent of stage migration using the FIGO 2018 staging system for cervical cancer and validate the new staging system by assessing the survival outcomes. Methods An Institutional Review Board-approved and Health Insurance Portability and Accountability Act-compliant retrospective analysis was performed on 158 patients from the cervical cancer database at the University of Mississippi Medical Center, USA. Patients had been treated between January 2010 and December 2018, and they were all staged according to the FIGO 2009 staging system previously. We collected data regarding tumor size, lymph node presence, and extent of metastatic disease in the pretreatment CT, positron emission tomography (PET), or MRI scans and restaged the patients using the FIGO 2018 system. The extent of stage migration was evaluated using the new staging system. We analyzed the three-year overall survival (OS) using both FIGO 2009 and 2018 staging systems for validation purposes. Kaplan-Meier analyses were performed using SPSS version 24. Results Fifty-nine percent of the patients were upstaged when they were restaged using the FIGO 2018 staging system. In the current 2018 staging system, Stage IB3 accounted for 4%, and Stage IIIC accounted for 48% of the patient cohort, while other stages accounted for the rest. The median overall survival of the entire cohort was 20.5 months. There was a change in the survival curves using FIGO 2018 stages compared to those of FIGO 2009. There was a numerical improvement in three-year OS in stages IB and III among the two staging systems; however, it was not statistically significant. Interestingly, the three-year overall survival of Stage IIIC patients was better when compared to Stages III A& B combined (61% vs. 25%, p=0.017). Conclusion The increased availability of cross-sectional imaging across the world has led to recent changes in the FIGO staging system for cervical cancer, which allowed imaging in staging. We identified a significant stage migration in our patient cohort with the FIGO 2018 staging system, but no difference in the three-year overall survival was observed. Local tumor extent may be a worse prognostic indicator than nodal metastasis among stage III patients.

Single Institution Experience of Stereotactic Body Radiation Therapy in Non-small Cell Lung Cancer: Comparison of Two Dose Regimes and a Perspective on Ideal Dose Regimens.

Introduction Stereotactic body radiation therapy (SBRT) is an effective treatment for early-stage non-small cell lung cancer (NSCLC) patients who are either medically inoperable or who decline surgery. SBRT improves tumor control and overall survival (OS) in medically inoperable, early-stage, NSCLC patients. In this study, we investigated the effectiveness of two different SBRT doses commonly used and present our institutional experience. Purpose To determine the clinical outcomes between two treatment regiments (50 Gray [Gy] vs. 55 Gy in five fractions) among Stage I NSCLC patients treated with SBRT at a state academic medical center. Methods We performed a retrospective analysis of 114 patients with Stage I (T1-2 N0 M0) NSCLC treated at a state academic medical center between October 2009 and April 2019. Survival analyses with treatment regimens of 50 Gy and 55 Gy in five fractions were conducted to detect any improvement in outcomes associated with the higher dose. The primary endpoints of this study included OS, local control (LC), and disease-free survival (DFS). Log-rank test and the Kaplan-Meier method were used to analyze the survival curves of the two treatment doses. The SPSS v.24.0 (IBM Corp., Armonk, NY, USA) was used for statistical analyses. Results The 114 early-stage NSCLC patients (median age, 68 years; range 12 to 87 years) had a median follow-up of 25 months (range two to 86 months). The number of males (n = 72; 63.2 %) exceeded the number of females (n = 42; 36.8 %). The majority of patients in this study were Caucasians (n = 68; 59.6 %) and 46 patients were African Americans (40.4 %). Two-thirds of the patients (n = 76; 66.7 %) were treated with 50 Gy in five fractions, and 38 patients (33.3 %) with 55 Gy in five fractions. The one-, two-, and three-year OS and DFS rates were improved in the patients treated with 55 Gy [OS, 81.7 % vs. 72.8 %; 81.7 % vs. 58.9 %; 81.7 % vs. 46.7 % (p = 0.049)], [DFS, 69.7 % vs. 69.7 %; 61.9 % vs. 55.7 %; 61.9 % vs. 52.0 % (p = 0.842)], compared to those treated with 50 Gy. Adenocarcinoma was the most common histology in both groups (51.3 % and 68.4 %). Failure rates were elevated for the 50 Gy regimen [39 (34.2 %) vs. 12 (8.5 %)]. Three year control rates were (66.3 % vs. 96.6 %; p = 0.002) local control; (63.3 % vs. 94.4 %; p = 0.000) regional control; and (65.7 % vs. 97.1 %; p = 0.000) distant control, compared to those treated with 55 Gy. Conclusion Early-stage NSCLC patients treated with SBRT 55 Gy in five fractions did better in terms of local control, overall survival, and disease-free survival rates compared to the 50 Gy in five fractions group.

Quality-Adjusted Life Years and Disability-Adjusted Life Years Are Better With Concurrent Chemoradiation Therapy Than Induction Chemotherapy Followed by Chemoradiation Therapy in Nasopharyngeal Carcinoma.

Introduction As traditional measures such as overall survival (OS) or disease-free survival (DFS) alone do not give a holistic view of the outcomes of a treatment paradigm, we determine to add the evidence of quality-adjusted life year (QALY) and disability-adjusted life year (DALY) to the outcomes of the nasopharyngeal carcinoma patients (NCP) treated with definitive chemoradiation therapy (chemoRT) with or without induction chemotherapy (induction chemo). Methods This is a retrospective analysis of 85 NCPs treated at an academic state institution. The OS estimated by the Kaplan-Meier method and the multivariate Cox regression model determined the co-variables associated with the OS. The relationship between QALYs gained and DALYs saved were calculated from age of the disease onset, duration of the disease, quality of life (QoL) and disability weights. Results Of the 85 eligible NCPs of this cohort, the disease frequency distribution per the World Health Organization (WHO) classification was 41.2% for Type-I, 42.4% for Type-II, and 16.5% for Type-III. The median follow-up (24 months). The five-year OS of patients treated with concurrent chemoRT vs. induction chemo followed by concurrent chemoRT was 54.7 vs. 14.8% for WHO Type I, 60.1 vs. 58.3% for WHO Type II, and 83.3 vs. 50.0% for WHO Type III (p=0.029). The average DALYs saved with concurrent chemoRT were 12.2 years vs. 5 years for induction chemo followed by concurrent chemoRT. The average QALYs gained with concurrent chemoRT were 6.9 years vs. 3.1 years for induction chemo followed by concurrent chemoRT. Conclusion Patients treated with concurrent chemoRT had an increased QoL when compared to induction chemo followed by concurrent chemoRT. The average DALYs saved were higher in the patients treated with concurrent chemoRT than treated with induction chemo followed by concurrent chemoRT.

An Analysis of the Racial Disparities Among Cervical Cancer Patients Treated at an Academic Medical Center in the Southeastern United States.

Objective The purpose of this study was to identify racial disparities in treatment outcomes, if any, among patients with carcinoma of the cervix treated at a tertiary care institution in the state of Mississippi. Methods A retrospective review of patients with carcinoma of the cervix treated in the Department of Radiation Oncology at our institution between 2010 and 2018 was performed. Data regarding demographics, disease stage, treatments administered, and follow-up were collected. Patient outcomes, including median survival and overall survival, were analyzed using the Kaplan-Meier method. All analyses were performed using SPSS Statistics version 24 (IBM, Armonk, NY). Results Between January 2010 and December 2018, a total of 165 patients with carcinoma of the cervix were treated at our institution. We had a significantly higher proportion of African American (AA) compared to Caucasian American (CA) patients (59.4 vs. 36.4%; p=0.03). There was a significant difference in the disease stage at the time of presentation between AA and CA in that compared to AA women, a higher number of CA patients presented with locally advanced disease [Federation of Gynecology and Obstetrics (FIGO) stages IB2 to IVA] (78.6 vs. 86.7%; p<0.001). However, a higher number of AA patients presented with metastatic disease at diagnosis compared to CA women (13.3 vs. 8.3%; p<0.001). Regarding their treatment, 157 (95.2%) underwent definitive chemoradiotherapy, while three (1.8%) had definitive surgery followed by adjuvant radiation or chemoradiation, depending on the risk factors identified operatively. The treatment details of five patients were not available. The median follow-up and the median survival of the entire cohort were 16 months and 79 months, respectively. In our cohort, there was no significant difference in overall survival between AA and CA patients at either three years (80 vs. 68%; p=0.883) or five years (77 vs. 68%; p=0.883). As expected, patients with locally advanced disease showed a significantly better median survival of 79 months compared to only 11 months for those with metastatic disease at their presentation (p<0.001). Conclusions Our study revealed that more AA women presented with metastatic disease compared to CA women. However, our analysis did not identify any racial disparities in the prognosis of the entire cohort.

A 25-year Experience at an Academic Medical Center in the United States: Are There Racial Disparities in the Prognosis of Patients Diagnosed With Hypopharyngeal Carcinoma?

Introduction This study attempted to identify disparities in outcomes between African American (AA) and Caucasian American (CA) patients treated for hypopharyngeal carcinoma at a tertiary care institution over the past 25 years. Methods An institutional review board (IRB)-approved and Health Insurance Portability and Accountability Act (HIPPA)-compliant retrospective analysis was performed on patients with squamous cell carcinoma of the hypopharynx treated at our institution between January 1994 and December 2018. Data regarding demographics, stage, treatment, and follow-up were collected. Outcomes, including median survival and overall survival, were calculated using the Kaplan-Meier method. All analyses were performed using the Social Packages for the Social Sciences (SPSS) v. 24 (IBM Corp., Armonk, NY). Results We identified 144 hypopharyngeal carcinoma patients who were treated during this period. Our patient cohort consisted of 61.8% AA and 35.4% CA (P=0.538). Overall, 96% of them presented at an advanced stage (Stages III & IV) of the disease, and only 4% presented in the early stages (Stages I & II). There was no significant difference between AA and CA patients who presented with advanced disease (96.6% vs. 94.1%). In our patient cohort, 15.3% of patients did not receive any therapy; however, 51.4%, 22.9%, and 10.4% of them underwent definitive chemoradiotherapy, definitive surgery, or palliative chemotherapy, respectively. There were no significant differences in patient racial proportions within each treatment group. The median follow-up of the entire cohort was 13 months. There was no significant difference between the median survival of AA and that of CA patients (16 months vs. 15 months; p=0.917). Moreover, there was no significant difference in the overall survival between AA and CA patients at three years (27.2% vs. 36.3%; p=0.917) and five years (20.4 % vs. 16.7 %; p=0.917). Conclusions A retrospective review of patients with hypopharyngeal cancer treated at our institution over the previous 25 years did not identify significant racial disparities regarding the stage at presentation or prognosis. This study suggests that when patients have equal access to care, they appear to have a similar prognosis despite racial differences. Further studies are needed to validate this hypothesis.

Chasing Zero Harm in Radiation Oncology: Using Pre-treatment Peer Review.

Purpose: The Joint Commission has encouraged the healthcare industry to become "High Reliability Organizations" by "Chasing Zero Harm" in patient care. In radiation oncology, the time point of quality checks determines whether errors are prevented or only mitigated. Thus, to "chase zero" in radiation oncology, peer review has to be implemented prior to treatment initiation. A multidisciplinary group consensus peer review (GCPR) model is used pre-treatment at our institution and has been successful in our efforts to "chase zero harm" in patient care. Methods: With the GCPR model, policy-defined complex cases go through a treatment planning conference, which includes physicians, residents, physicists, and dosimetrists. Three major plan aspects are reviewed: target volumes, target and normal tissue dose coverage, and dose distributions. During the review, any team member can ask questions and afterwards a group consensus is taken regarding plan approval. Results: The GCPR model has been implemented through a commitment to peer review and creative conference scheduling. Automated analysis software is used to depict color-coded results for department approved target coverage and dose constraints. About 8% of plans required re-planning while about 23% required minor changes. The mean time for review of each plan was 8 min. Conclusions: Catching errors prior to treatment is the only way to "chase zero" in radiation oncology. Various types of errors may exist in treatment plans and our GCPR model succeeds in preventing many errors of all shapes and sizes in target definition, dose prescriptions, and treatment plans from ever reaching the patients.

Stereotactic Body Radiation Therapy for Stage I Non-Small Cell Lung Cancer: A Retrospective, Single-Center Study of 55 Patients.

Purpose/Objective(s): Stereotactic body radiation therapy (SBRT) is an effective treatment for patients with early-stage non-small cell lung cancer (NSCLC) who are not surgical candidates or who refuse surgical management. In this study, we report on our clinical outcomes and toxicity in the treatment of early-stage NSCLC with SBRT. METHODS AND MATERIALS: Fifty-five patients with 59 T1-2N0M0 NSCLC lesions were treated at our institution between December 2009 and August 2014. The majority of the patients [38 (69%)] were treated with 50 Gy in 5 fractions, 7 patients (13%) with 48 Gy in 4 fractions, 8 patients (14%) with 60 Gy in 3 fractions, 1 patient (2%) with 62.5 Gy in 10 fractions, and 1 patient (2%) with 54 Gy in 3 fractions. Tumor response was evaluated using RECIST 1.1, and toxicity was graded using the CTCAE (Common Terminology Criteria for Adverse Events) version 3.0. The primary endpoints of this retrospective review included rates of overall survival, disease-free and progression-free survival, local failure, regional failure, and distant failure. A secondary endpoint included radiation-related toxicities. RESULTS: The median follow-up was 23.8 months (range 1.1-57.6). The 3-year local control, progression-free survival, and overall survival rates were 91, 55, and 71%, respectively. The median age at diagnosis was 67.9 years (range 51.4-87.1). There were a total of 54 T1N0 tumors (92%) and 5 T2N0 lesions (8%). Adenocarcinoma was the most common pathology, comprising 54% of the lesions. A total of 16 of the patients (29%) failed. Among these, 5 local (9%), 14 regional (25%), and 4 distant failures (7%) were observed. On follow-up, one patient had grade 2 and another had grade 5 pneumonitis. Three patients experienced grade 2 chest wall tenderness. Two patients had grade 1 rib fractures, one of which could not be discerned from radiation-induced toxicity versus a traumatic fall. CONCLUSION: The University of Mississippi Medical Center SBRT experience has shown that SBRT provides satisfactory local control and overall survival rates with minimal toxicity in early-stage NSCLC patients.

Computerized tomography-based radiotherapy improves heterotopic ossification outcomes.

PURPOSE: To report the impact of computerized tomography (CT) based radiotherapy (RT) on heterotopic ossification (HO) outcomes. METHODS: This is a single institution, retrospective study of 532 patients who were treated for traumatic acetabular fractures (TAF). All patients underwent open-reduction internal-fixation (ORIF) of the TAF followed by RT for HO prophylaxis. Postoperative RT was delivered within 72h, in a single fraction of 7Gy. The patients were divided into 2 groups based on RT planning: CT (A) vs. clinical setup (B). RESULTS: At a median follow up of 8years the incidence of HO was 21.6%. Multivariate regression analysis revealed that group (A) vs. (B) had HO incidence of 6.6% vs. 24.6% (p<0.001), respectively. Furthermore, HO Brooker grade ≥3 was observed in 2.2% vs. 10.8% (p=0.007) in group (A) vs. (B), respectively. Thus, the odds of developing HO and Brooker grades ≥3 were 4.7 and 4.5 times higher, respectively, in patients who underwent clinical setup. CONCLUSION: Our data suggest that using CT based RT allowed more accurate delineation of the tissues and better clinical outcomes. Although CT-based RT is associated with additional cost the efficacy of CT-based RT reduces the risk of HO, thereby decreasing the need for additional surgical interventions.

The influence of pregnancy on heterotopic ossification post-displaced acetabular fractures surgical repair.

Pregnancy is associated with maternal bone mineral density loss and modulation of calcium metabolism. We hypothesized that pregnancy may decrease the risk of heterotopic ossification (HO) after trauma. This is a single-institution, University of Mississippi Medical Center, retrospective study investigating the effect of pregnancy on the incidence HO after surgical repair (SR) of displaced acetabular fractures. Between January 1998 and 2010, 257 non-pregnant women (Group A) and 16 pregnant women (Group B) were identified. All the non-pregnant women received radiation therapy (RT) ± indomethacin. None of the pregnant women in group B received any prophylaxis. After a median follow-up of 6.6 years the incidence of HO in all patients was 27% (75/273). In Group A, non-pregnant, women who received RT ± indomethacin, 29% developed HO; HO risk was 0.4. In Group B, 16 pregnant patients, only one developed HO (6%); HO risk was 0.06. Thus, the risk of HO appears to be nearly six-fold higher in non-pregnant women despite prophylactic RT ± indomethacin. Our data suggest that pregnancy may be associated with a reduced risk of HO after SR of displaced acetabular fractures. Further analysis with a larger pregnant patient sample is necessary to confirm this finding.

The impact of body mass index on heterotopic ossification.

PURPOSE: To analyze the impact of different body mass index (BMI) as a surrogate marker for heterotopic ossification (HO) in patients who underwent surgical repair (SR) for displaced acetabular fractures (DAF) followed by radiation therapy (RT). METHODS AND MATERIALS: This is a single-institution retrospective study of 395 patients. All patients underwent SR for DAF followed by RT ± indomethacin. All patients received postoperative RT, 7 Gy, within 72 h. The patients were separated into four groups based on their BMI: <18.5, 18.5-24.9, 25-29.9, and >30. The end point of this study was to evaluate the efficacy of RT ± indomethacin in preventing HO in patients with different BMI. RESULTS: Analysis of BMI showed an increasing incidence of HO with increasing BMI: <18.5, (0%) 0/6 patients; 18.5-24.9 (6%), 6 of 105 patients developed HO; 25-29.9 (19%), 22 of 117; >30 (31%), 51 of 167. Chi-square and multivariate logistic regression analysis showed that the correlation between odds of HO and BMI is significant, p < 0.0001. As the BMI increased, the risk of HO and Brooker Classes 3, 4 HO increased. The risk of developing HO is 1.0× (10%) more likely among those with higher BMI compared with those with lower BMI. For a one-unit increase in BMI the log odds of HO increases by 1.0, 95% CI (1.06-1.14). Chi-square test shows no significant difference among all other factors and HO (e.g., indomethacin, race, gender). CONCLUSIONS: Despite similar surgical treatment and prophylactic measures (RT ± indomethacin), the risk of HO appears to significantly increase in patients with higher BMI after DAF. Higher single-fraction doses or multiple fractions and/or combination therapy with nonsteroidal inflammatory drugs may be of greater benefit to these patients.

The impact of class III (morbid) obesity on heterotopic ossification outcomes.

PURPOSE: Obesity is associated with a chronic low inflammatory process that may act as common soil for the pathogenesis of obesity-related comorbidities including heterotopic ossification (HO). The purpose of this study is to compare the incidence of HO between patients with body mass index (BMI) <40 versus ≥40 after operative treatment of displaced acetabular fractures followed by radiation therapy (RT) ± indomethacin. METHODS AND MATERIALS: This is a single institution retrospective chart review of 419 patients. All patients with well-documented BMI underwent operative treatment followed by RT ± indomethacin. All patients received 700 cGy to the soft tissues around the proximal femur and acetabulum without bone shielding. All RT were given postoperatively within 72 hours. The patients were divided into 2 groups: Group (A) BMI < 40 and Group (B) BMI ≥40. HO was assessed with X-ray. BMI was used as a surrogate measure to test the risk of HO despite prophylaxis. RESULTS: The incidence of HO among all patients is 21% (89 of 419), while among those in group A (BMI <40), 68 of 374 patients developed HO (18%); in the morbidly obese group (BMI ≥40) 21of 45 patients developed HO (47%). The difference between the rates of HO in the 2 groups was 29%; the χ(2) test showed a significant difference between the 2 BMI groups (P < .001 at α = 0.05). CONCLUSIONS: There is a higher incidence of HO among the morbidly obese patients despite RT ± indomethacin. RT doses for HO prophylaxis in morbidly obese patients need to be reassessed; also, understanding the signaling pathways in target tissues in obese patients at which adipokines control metabolism may reveal novel therapies. Higher radiation doses ± indomethacin may need to be considered and optimally evaluated in the context of a prospective, randomized clinical trial.