•Patient education and expansion of nontraditional screening programs for unscreened and underscreened populations.•Implement reduction in costs, government health programs, and school based programs ...for vaccinations.•Adhere to guidelines, ensure access to healthcare, and establish an ethnically similar physician workforce for all patients.•Improve training, work efficiencies, payment reform, and quality metrics.•Ensure widespread use of chemoradiation, identify targets, and develop mutation-specific trials.
One woman dies from cervix cancer every 2 min, adding up to over 270,000 deaths globally per year. This cancer affects a young population, and hence, the loss of life is staggering. There are many aspects of prevention, screening, and care that are suboptimal. A great deal is known about HPV induced carcinogenesis, yet clinical outcomes have been stagnant over decades. There has been no improvement in cervix cancer survival in the US since the mid-1970s 1. With increased knowledge of the disease and greater worldwide resources including prevention, screening, and improved therapeutics, there is significant promise for fewer women to die from this virally induced cancer. We focus here on the major problems in prevention, screening, and delivery of care for cervix cancer and provide concrete solutions. With appropriate focus, a major improvement in survival from cervix cancer could be achieved in a short time span.
Purpose NRG Oncology/RTOG 1203 was designed to compare patient-reported acute toxicity and health-related quality of life during treatment with standard pelvic radiation or intensity-modulated ...radiation therapy (IMRT) in women with cervical and endometrial cancer. Methods Patients were randomly assigned to standard four-field radiation therapy (RT) or IMRT radiation treatment. The primary end point was change in patient-reported acute GI toxicity from baseline to the end of RT, measured with the bowel domain of the Expanded Prostate Cancer Index Composite (EPIC). Secondary end points included change in patient-reported urinary toxicity, change in GI toxicity measured with the Patient-Reported Outcome Common Terminology Criteria for Adverse Events, and quality of life measured with the Trial Outcome Index. Results From 2012 to 2015, 289 patients were enrolled, of whom 278 were eligible. Between baseline and end of RT, the mean EPIC bowel score declined 23.6 points in the standard RT group and 18.6 points in the IMRT group ( P = .048), the mean EPIC urinary score declined 10.4 points in the standard RT group and 5.6 points in the IMRT group ( P = .03), and the mean Trial Outcome Index score declined 12.8 points in the standard RT group and 8.8 points in the IMRT group ( P = .06). At the end of RT, 51.9% of women who received standard RT and 33.7% who received IMRT reported frequent or almost constant diarrhea ( P = .01), and more patients who received standard RT were taking antidiarrheal medications four or more times daily (20.4% v 7.8%; P = .04). Conclusion Pelvic IMRT was associated with significantly less GI and urinary toxicity than standard RT from the patient's perspective.
Accurate target definition is critical for the appropriate application of radiation therapy. In 2008, the Radiation Therapy Oncology Group (RTOG) published an international collaborative atlas to ...define the clinical target volume (CTV) for intensity modulated pelvic radiation therapy in the postoperative treatment of endometrial and cervical cancer. The current project is an updated consensus of CTV definitions, with removal of all references to bony landmarks and inclusion of the para-aortic and inferior obturator nodal regions.
An international consensus guideline working group discussed modifications of the current atlas and areas of controversy. A document was prepared to assist in contouring definitions. A sample case abdominopelvic computed tomographic image was made available, on which experts contoured targets. Targets were analyzed for consistency of delineation using an expectation-maximization algorithm for simultaneous truth and performance level estimation with kappa statistics as a measure of agreement between observers.
Sixteen participants provided 13 sets of contours. Participants were asked to provide separate contours of the following areas: vaginal cuff, obturator, internal iliac, external iliac, presacral, common iliac, and para-aortic regions. There was substantial agreement for the common iliac region (sensitivity 0.71, specificity 0.981, kappa 0.64), moderate agreement in the external iliac, para-aortic, internal iliac and vaginal cuff regions (sensitivity 0.66, 0.74, 0.62, 0.59; specificity 0.989, 0.966, 0.986, 0.976; kappa 0.60, 0.58, 0.52, 0.47, respectively), and fair agreement in the presacral and obturator regions (sensitivity 0.55, 0.35; specificity 0.986, 0.988; kappa 0.36, 0.21, respectively). A 95% agreement contour was smoothed and a final contour atlas was produced according to consensus.
Agreement among the participants was most consistent in the common iliac region and least in the presacral and obturator nodal regions. The consensus volumes formed the basis of the updated NRG/RTOG Oncology postoperative atlas. Continued patterns of recurrence research are encouraged to refine these volumes.
The 2018 International Federation of Gynecology and Obstetrics (FIGO) staging system for cervical cancer changed from a clinical system to a clinical/pathologic/radiologic system with stages IIIC1 ...and IIIC2 indicating positive pelvic and para-aortic lymph nodes, respectively. We evaluated the National Cancer Database (NCDB) for the impact on survival of lymph node metastases (LNM).
The NCDB from 2004 to 2015 was queried for patients with cervical cancer, yielding 115,819 patients. Patients with FIGO IVB (22,569), non-adeno/squamous cell histologies (5,909), unknown nodal status (60,695), or unknown survival time (9,473) were excluded. Survival was compared using Cox proportional hazard model based on nodal status. Univariate (UVA) and multivariate analyses (MVA) were done for the overall cohort, followed by UVA by individual stage.
In 17,173 eligible patients, LNM negatively affected survival (UVA IIIC1 Hazard Ratio HR 2.0, p < 0.001, IIIC2 HR 3.9, p < 0.001, MVA IIIC1 HR 1.36, p < 0.001, IIIC2 HR 2.14, p < 0.001). In T1B, the effect of IIIC2 was most pronounced (HR 5.38, p < 0.001 versus HR 1.5 p = 0.001 for IIIC1 disease). In T3, the effect of LNM was markedly less: (HR 1.7, p < 0.001 for IIIC2 versus HR 1.2 p = 0.02 for IIIC1). Within T1B, there was no difference in survival for IIIC1 for the smaller T stages (IB1-2).
In this study, LNM negatively affects prognosis in cervical cancer. The impact on survival varies by T stage with the greatest effect seen in stage T1B with IIIC2 disease.
•Prognosis in cervical cancer is negatively affected by the presence of lymph node metastases (LNM).•The effect of LNM is variable by T stage.•Large cervix primaries are affected less by lymph node metastases.•Para-aortic LNM can have a large survival decrement particularly in smaller tumors.
To analyze our institutional experience and oncologic outcomes for salvage treatment for the recurrence of early-stage endometrial cancer patients.
We included women of all ages diagnosed with FIGO ...stage I-II, any grade endometrial cancer from 2000 to 2016 at our institutions who were treated with at least a hysterectomy. Recurrences in the pelvis and/or vagina were considered locoregional recurrences (LRR). Overall survival (OS) was assessed using Kaplan-Meier survival analysis. Univariate (UV) and multivariate (MV) Cox proportional hazards modeling was also used.
A total of 2691 women were analyzed. The majority had endometrioid histology (91%), stage IA disease (61%), and were grade 1 (57%). With a median follow-up of 6.1 years, the overall rate of recurrence was 7.2%, and the rate of LRR was 3.7%. Women with vaginal-only recurrences had a longer median OS after recurrence (14.0 years) compared to both pelvic (1.2 years) and distant (1.0 year) failures. For women with vaginal-only recurrences, salvage radiotherapy (RT) was the only factor associated with improved OS on MVA (HR 0.1, p = .04). For women with pelvic recurrences, salvage surgery (HR 0.3, p = .01), salvage RT (HR 0.3, p < .01), and salvage chemotherapy (HR 0.4, p = .03) were associated with improved OS.
Failure rates for women with early-stage endometrial cancer are low. Women with vaginal-only recurrences have improved OS compared to pelvic or distant recurrences. Salvage RT appears to be an important factor for treatment of women with vaginal-only recurrences. Aggressive multimodality treatment may be beneficial for women with pelvic recurrences.
•Women with vaginal recurrences had significantly longer survival than women with pelvic or distant recurrences.•Salvage radiotherapy was the only factor we found associated with improved survival for vaginal recurrences.•Salvage surgery, radiotherapy, and chemotherapy were associated with improved survival for pelvic recurrences.•In the rare situation of a second locoregional recurrence, 50% of patients can be salvaged at 5 years.
The International Federation of Gynecology and Obstetrics (FIGO) staging system for endometrial cancer underwent revision in 2023, incorporating histology, lymphovascular space invasion, and ...molecular classification. Herein, we compare overall survival (OS) outcomes by anatomic and histologic involvement for patients staged by the 2009 system versus 2023 system.
The National Cancer Database (NCDB) was queried for patients with newly-diagnosed uterine adenocarcinoma from 2004 to 2015, with follow-up data extending through 2020. Stage was determined by both the 2009 and 2023 FIGO staging systems. Kaplan-Meier estimators and Cox proportional hazards models were used for survival analysis.
A total of 134,677 patients were analyzed. Per 2023 classification, patients with stage I disease decreased from 96,161 to 70,101 (−27.1%, p < 0.01), while stage II disease increased from 9295 to 36,294 (+390.5%, p < 0.01). Greatest OS change was observed for 2023 stage IA3 patients (low-risk, synchronous endometrial and ovarian tumors with a clonal relationship), whose 10-year OS was 73.4%, compared to 52.6% for 2009 stage IIIA disease. Ten-year OS for 2023 stage IIIB2 (pelvic peritoneal involvement), previously 2009 stage IVB, was 49.4%, compared to 18.7% for 2009 stage IVB patients. Akaike information criterion, Bayesian information criterion, and Harrel’s concordance index were used to evaluate OS prognostication of each staging system across all stages, with likelihood ratio favoring the 2023 system (p = 0.020).
With FIGO’s 2023 endometrial cancer anatomic and histologic staging system, stage migration is greatest in early-stage disease. New staging groups may offer more precise prognostication. These changes may affect future management.
•FIGO’s 2023 endometrial cancer staging system adds many variables and stage groups.•Stage migration using this new system is greatest in stage I and II disease.•Discrimination of survival appears to be more precise using 2023 classifications.•Molecular testing should play an increasingly important role in clinical decisions.•Staging changes will likely affect practice paradigms in the coming years.
In oncology trials, the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) is the standard tool for reporting adverse events (AEs), but it may underreport symptoms ...experienced by patients. This analysis of the NRG Oncology RTOG 1203 compared symptom reporting by patients and clinicians during radiotherapy (RT).
Patients with cervical or endometrial cancer requiring postoperative RT were randomly assigned to standard 4-field RT or intensity-modulated RT (IMRT). Patients completed the 6-item patient-reported outcomes version of the CTCAE (PRO-CTCAE) for GI toxicity assessing abdominal pain, diarrhea, and fecal incontinence at various time points. Patients reported symptoms on a 5-point scale. Clinicians recorded these AEs as CTCAE grades 1 to 5. Clinician- and patient-reported AEs were compared using McNemar's test for rates > 0%.
Of 278 eligible patients, 234 consented and completed the PRO-CTCAE. Patients reported high-grade abdominal pain 19.1% (
< .0001), high-grade diarrhea 38.5% (
< .0001), and fecal incontinence 6.8% more frequently than clinicians. Similar effects were seen between grade ≥ 1 CTCAE toxicity and any-grade patient-reported toxicity. Between-arm comparison of patient-reported high-grade AEs revealed that at 5 weeks of RT, patients who received IMRT experienced fewer GI AEs than patients who received 4-field pelvic RT with regard to frequency of diarrhea (18.2% difference;
= .01), frequency of fecal incontinence (8.2% difference;
= .01), and interference of fecal incontinence (8.5% difference;
= .04).
Patient-reported AEs showed a reduction in symptoms with IMRT compared with standard RT, whereas clinician-reported AEs revealed no difference. Clinicians also underreported symptomatic GI AEs compared with patients. This suggests that patient-reported symptomatic AEs are important to assess in this disease setting.
To assess risks of secondary malignancies in breast cancer patients who received radiation therapy compared to patients who did not.
The SEER database was used to identify females with a primary ...diagnosis of breast cancer as their first malignancy, during 1973–2008. We excluded patients with metastatic disease, age <18 years, no definitive surgical intervention, ipsilateral breast cancer recurrence, or who developed a secondary malignancy within 1 year of diagnosis. Standardized incidence ratios and absolute excess risk were calculated using SEER*Stat, version 8.2.1 and SAS, version 9.4.
There were 374,993 patients meeting the inclusion criteria, with 154,697 who received radiation therapy. With a median follow-up of 8.9 years, 13% of patients (49,867) developed a secondary malignancy. The rate of secondary malignancies was significantly greater than the endemic rate in breast cancer patients treated without radiation therapy, (O/E 1.2, 95% CI 1.19–1.22) and with radiation therapy (O/E 1.33, 95% CI 1.31–1.35). Approximately 3.4% of secondary malignancies were attributable to radiation therapy. The increased risk of secondary malignancies in breast cancer patients treated with radiation therapy compared to those without was significant regardless of age at breast cancer diagnosis (p < 0.01) and more pronounced with longer latency periods.
There was an increased risk of secondary malignancies for breast cancer patients both with and without radiation therapy compared to the general population. There was an increased risk in specific sites for patients treated with radiation therapy. This risk was most evident in young patients and who had longer latency periods.
•This study provides data on secondary cancer risk with breast cancer treatment.•Approximately 6.5% of secondary cancers were attributable to radiation.•Radiation attributed to approximately 9.6% of contralateral breast cancers.•There is a small increased risk of secondary cancers with the addition of RT.
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