Ablative Radiation Therapy to Restrain Everything Safely Treatable (ARREST): A Phase I study of Stereotactic Ablative Radiotherapy (SABR) for poly-metastatic disease.

PURPOSE: This phase 1 study aimed to assess the safety and feasibility of SABR delivery to all sites of polymetastatic disease (>10 metastases). METHODS AND MATERIALS: A 3+3 study design was used with five dose levels from 6 Gy (6 Gy x 1) to 30 Gy (6 Gy weekly x 5). Dose-limiting toxicity (DLT) was defined as any grade 4 or 5 toxicity, or more than three grade 3 toxicities within six weeks of treatment. The primary endpoint was the maximal tolerated dose, defined as the dose level where ≥ 2/6 of patients experienced DLT. Secondary endpoints included quality of life (QOL; FACT-G and EQ-5D-5L) at 6-weeks post-treatment, progression-free survival (PFS) and overall survival (OS). RESULTS: Thirteen patients were accrued: 12 Gy (n=3), 18 Gy (n=3), 24 Gy (n=4), 30 Gy (n=3) and 207 lesions were treated. Nine patients (69%) had acute toxicity: grade 1 (n=6, 46%), grade 2 (n=2, 15%; n=1 pneumonitis and n=1 fatigue) and grade 3 (n=1, 7.7%, neutropenia). There were no grade 4 or 5 toxicities. Mean ± SD QOL (FACT-G and EQ-5D-5L health state) was 80.4 ± 21.9 and 77.4 ± 20.9 at baseline versus 76.4 ± 21.8 and 68.0 ± 24.2 at 6-week follow-up (p=0.009 and p=0.055, respectively). With a median follow-up of 8.7 months post-treatment (IQR: 2.4-24 months), 8 of 13 patients had disease progression (62%). The median and 12-month PFS were 3.6 months and 11.3% respectively. The median and 12-month OS were 13.8 months and 62% respectively. CONCLUSIONS: In this phase I trial, SABR for polymetastatic disease was technically feasible with acceptable acute toxicity at dose levels up to 30 Gy (6 Gy weekly x 5). DLT was not observed.

Salvage prostate brachytherapy in radiorecurrent prostate cancer: An international Delphi consensus study.

BACKGROUND AND PURPOSE: Local recurrences after previous radiotherapy (RT) are increasingly being identified in biochemically recurrent prostate cancer. Salvage prostate brachytherapy (BT) is an effective and well tolerated treatment option. We sought to generate international consensus statements on the use and preferred technical considerations for salvage prostate BT. MATERIALS AND METHODS: International experts in salvage prostate BT were invited (n = 34) to participate. A three-round modified Delphi technique was utilized, with questions focused on patient- and cancer-specific criteria, type and technique of BT, and follow-up. An a priori threshold for consensus of ≥ 75% was set, with a majority opinion being ≥ 50%. RESULTS: Thirty international experts agreed to participate. Consensus was achieved for 56% (18/32) of statements. Consensus was achieved in several areas of patient selection: 1) A minimum of 2-3 years from initial RT to salvage BT; 2) MRI and PSMA PET should be obtained; and 3) Both targeted and systematic biopsies should be performed. Several areas did not reach consensus: 1) Maximum T stage/PSA at time of salvage; 2) Utilization/duration of ADT; 3) Appropriateness of combining local salvage with SABR for oligometastatic disease and 4) Repeating a second course of salvage BT. A majority opinion preferred High Dose-Rate salvage BT, and indicated that both focal and whole gland techniques could be appropriate. There was no single preferred dose/fractionation. CONCLUSION: Areas of consensus within our Delphi study may serve as practical advice for salvage prostate BT. Future research in salvage BT should address areas of controversy identified in our study.

A Prospective Study of Magnetic Resonance Imaging-guided Focal Salvage High-dose-Rate Brachytherapy for Radiorecurrent Prostate Cancer: Updated Results of 30 Patients.

PURPOSE: Limited prospective data on focal salvage high-dose-rate (HDR) prostate brachytherapy is available. We sought to explore the toxicities, health-related quality of life (HRQoL), and efficacy of focal salvage HDR brachytherapy in a prospective clinical trial. This report presents the updated results of previously published data. METHODS AND MATERIALS: Patients with locally recurrent prostate cancer after previous external beam radiation therapy and/or brachytherapy were enrolled. Patients received magnetic resonance imaging (MRI)-guided, ultrasound-based focal HDR brachytherapy delivered over 2 fractions of 13.5 Gy delivered 1 to 2 weeks apart. Androgen deprivation therapy (ADT) was not used. RESULTS: Thirty patients were treated between 2012 and 2019. At a median follow-up time of 39 months, the 3-year biochemical failure-free rate was 61.8% (95% confidence interval, 44.0%-86.6%), and the 3-year ADT/salvage therapy-free rate was 86.0% (95% confidence interval, 74.1%-99.8%). Seventeen patients experienced subsequent biochemical failure, 9 received ADT and/or further local salvage, and no patients died of prostate cancer. Of the 28 patients who had posttreatment MRI, 26 had a local treatment response. No acute grade ≥3 genitourinary/gastrointestinal toxicity was observed. One temporary late grade 3 genitourinary toxicity event occurred, but no late grade ≥3 gastrointestinal toxicity was seen. No significant decline in urinary or bowel HRQoL was observed. CONCLUSIONS: Focal salvage HDR brachytherapy has a favorable side effect profile, no significant decline in HRQoL, and the 3-year biochemical control rates are in line with those of other salvage options. Early MRI response at the treated site is common, but does not preclude subsequent biochemical failure.

Radiation Oncologist Consultations Prior to Radical Prostatectomy: Disparities and Opportunities.

PURPOSE: In 2015, men undergoing radical prostatectomy in Ontario, Canada were recommended to undergo multidisciplinary care by seeing a radiation oncologist or discussion at multidisciplinary rounds before surgery. The a priori target rate was ≥76%. We used population-based data to explore factors associated with not receiving multidisciplinary care prior to radical prostatectomy. MATERIALS AND METHODS: Men who underwent radical prostatectomy for localized prostate cancer in Ontario between 2007 and 2017 were identified using administrative data. Physician billings identified patients who received multidisciplinary care. Multivariable logistic regression was used to predict receipt of multidisciplinary care. RESULTS: A total of 31,485 men underwent radical prostatectomy between 2007 and 2017. Of these patients 28.7% saw a radiation oncologist, 1.2% underwent multidisciplinary discussion and 1.9% had both before surgery. Multidisciplinary care receipt increased from 17.8% in 2007 to 47.8% in 2017 (p <0.001). The odds ratio between the highest and lowest geographic regions was 7.93 (95% CI 6.17-10.18, p <0.001). Lower odds of multidisciplinary care receipt were observed for men further from the nearest cancer center (OR 0.74 per 50 km, 95% CI 0.71-0.78, p <0.001) and higher odds for the highest versus lowest income quintile (OR 1.41, 95% CI 1.29-1.54, p <0.001). Of 128 urologists who performed ≥10 radical prostatectomies between 2016 and 2017, 29 (22.7%) met the target of having ≥76% of men seen for multidisciplinary care prior to surgery. CONCLUSIONS: Despite increasing utilization, many men do not receive multidisciplinary care prior to radical prostatectomy. While geography and the urologist appear to be the greatest factors predicting multidisciplinary care receipt, these factors are closely intertwined.

Defining radio-recurrent intra-prostatic target volumes using PSMA-targeted PET/CT and multi-parametric MRI.

PURPOSE: Our purpose was to evaluate intra-prostatic cancer volumes for salvage radiotherapy in men with recurrent prostate cancer confined to the prostate post-primary radiotherapy using mpMRI and 18F-DCFPyL PET/CT (PET). METHODS: Men with biochemical failure post-primary radiotherapy were enrolled in a multi-centre trial investigating mpMRI and PET. All men with isolated intra-prostatic recurrence are included in this secondary analysis. The intra-prostatic gross tumour volume (GTV) was manually delineated on mpMRI and was also delineated on PET using three methods: 1. manually, 2. using a 30% threshold of maximum intra-prostatic standard uptake value (SUVmax), and 3. using a 67% threshold of this SUVmax. Clinical target volumes (CTV) including expansions on each GTV were generated. Conformity indices were performed between the mpMRI CTV and each PET CTV. Correlation with biopsy and clinical outcomes were performed. RESULTS: Of the 36 men included, 30 (83%) had disease in two quadrants or less using the combination of mpMRI and PET. Mean target volume (union of CTV on mpMRI and CTV manually delineated on PET) was 12.2 cc (49% of prostate gland volume). 12/36 (33%) men had a biopsy. Per-patient sensitivity was 91% for mpMRI and 82% for PET. CONCLUSIONS: mpMRI and PET provide complementary information for delineation of intra-prostatic recurrent disease. Union of CTV on mpMRI and PET is often less than 50% of the prostate, suggesting this imaging could help define a target for focal salvage therapy.

Can Polymetastatic Disease Be ARRESTed Using SABR? A Dosimetric Feasibility Study to Inform Development of a Phase 1 Trial.

PURPOSE: Phase 2 randomized trials suggest that stereotactic ablative radiation therapy improves progression-free and overall survival in patients with oligometastatic cancer, with phase 3 trials currently testing stereotactic ablative radiation therapy in up to 10 metastases. Whether stereotactic radiation therapy could provide similar benefits in polymetastatic disease (>10 metastases) is unknown. We sought to evaluate the dosimetric feasibility of using stereotactic radiation therapy in polymetastatic disease in preparation for a phase 1 trial. METHODS AND MATERIALS: Five craniospinal computed tomography simulations were used to simulate 24 metastatic targets (n = 2 patients), 30 targets (n = 2 patients), and 50 targets (n = 1 patient) that were not present on the initial scan. Creation of radiation therapy plans was attempted for doses up to 30 Gy in 5 fractions, with de-escalation to 24 Gy/4, 18 Gy/3, 12 Gy/2, or 6 Gy/1 if not feasible based on standardized dose constraints. Plans were created using Raystation for delivery on linear accelerators using volumetric modulated arc therapy and validated using Mobius 3D. RESULTS: A stereotactic radiation therapy treatment plan was generated for each simulated patient. Dose constraints were met to a dose of 30 Gy in 5 fractions for the patients with 24 and 30 lesions. For the patient with 50 targets, dose de-escalation to 12 Gy in 2 fractions was required to meet lung constraints. Estimated beam-on time varied between 18 and 29 minutes per fraction of 6 Gy. Median D95 planning target volume dosimetry ranged from 96.6% to 97.7% of the prescription dose. The conformity index (R100) range was 0.89 to 0.95, and R50 range was 6.84 to 8.72. CONCLUSIONS: Stereotactic radiation therapy treatment plans meeting standardized dose constraints could be created in the setting of 24 to 50 metastatic lesions using volumetric modulated arc therapy. This safety of this approach is being evaluated in a phase 1 trial (NCT04530513).

Organ at Risk Dose Constraints in SABR: A Systematic Review of Active Clinical Trials.

PURPOSE: Organ at risk (OAR) dose constraints are a critical aspect of SABR treatment planning. There is limited evidence supporting preferred dose constraints for many OARs. We sought to evaluate OAR dose constraints used in ongoing clinical trials of SABR for oligometastatic disease. METHODS AND MATERIALS: Clinicaltrials.gov was searched from inception to February 2020 to capture actively accruing clinical trials using SABR in oligometastatic disease. Dose constraints were obtained by contacting principal investigators and abstracted by 2 authors. Variability of constraints was assessed by comparing the width of the interquartile range and difference between the maximum and minimum dose to a volume. RESULTS: Fifty-three of 85 eligible clinical trials contributed OAR constraints used in analysis. Dose constraints for 1 to 8 fractions of SABR were collected for 33 OARs. Variability was found in the absolute allowable OAR doses, use of planning OAR volumes, and whether constraints were optional versus mandatory. For many OARs, modal dose constraints often matched a pre-existing publication, but no single pre-existing publication matched the modes of all OAR dose constraints. Organs displaying the most variability were the rectum, penile bulb, and chest wall and ribs. The esophagus, stomach, duodenum, and small bowel also indicated high variability for at least 1 constraint. OARs previously evaluated by HyTEC appeared to have less variability among study protocols. CONCLUSIONS: We found substantial variability in OAR dose constraints used in current clinical trials evaluating SABR in oligometastatic disease. We are unable to comment on toxicity rates or acceptability of dose constraints used. Future research and recommendations for standardized OAR dose constraints, as well as consistency in implementing planning OAR volume margins, should be priorities for the field of radiation oncology.

Ablative radiation therapy to restrain everything safely treatable (ARREST): study protocol for a phase I trial treating polymetastatic cancer with stereotactic radiotherapy.

BACKGROUND: Patients with polymetastatic cancer are most often treated with systemic therapy to improve overall survival and/or delay progression, with palliative radiotherapy reserved for sites of symptomatic disease. Stereotactic ablative radiotherapy (SABR) has shown promise in the treatment of oligometastatic disease, but the utility of SABR in treating all sites of polymetastatic disease has yet to be evaluated. This study aims to evaluate the maximally tolerated dose (MTD) of SABR in patients with polymetastatic disease. METHODS: Up to 48 patients with polymetastatic cancer (> 10 sites) will be enrolled on this phase I, modified 3 + 3 design trial. Eligible patients will have exhausted (or refused) standard systemic therapy options. SABR will be delivered as an escalating number of weekly fractions of 6 Gy, starting at 6 Gy × 2 weekly fractions (dose level 1). The highest dose level (dose level 4) will be 6 Gy × 5 weekly fractions. Feasibility and safety of SABR will be evaluated 6 weeks following treatment using a composite endpoint of successfully completing treatment as well as toxicity outcomes. DISCUSSION: This study will be the first to explore delivering SABR in patients with polymetastatic disease. SABR will be planned using the guiding principles of: strict adherence to dose constraints, minimization of treatment burden, and minimization of toxicity. As this represents a novel use of radiotherapy, our phase I study will allow for careful selection of the MTD for exploration in future studies. TRIAL REGISTRATION: This trial was prospectively registered in ClinicalTrials.gov as NCT04530513 on August 28, 2020.

Prostate high dose-rate brachytherapy as monotherapy for prostate cancer: Late toxicity and patient reported outcomes from a randomized phase II clinical trial.

BACKGROUND AND PURPOSE: Long-term toxicity of high dose-rate brachytherapy as monotherapy for prostate cancer is not well defined. We report late toxicity and health related quality of life (HRQOL) changes from a randomized phase II clinical trial of two different fractionation schemes. MATERIALS AND METHODS: Eligible patients had NCCN low or intermediate risk prostate cancer. 170 patients were randomized to receive either a single 19 Gy or two-fractions of 13.5 Gy one week apart. Toxicity was measured using Common Terminology for Adverse Events (CTCAE) v4.0, and HRQOL was measured using the Expanded Prostate Index Composite (EPIC). RESULTS: Median follow-up was 63 months. The 5-year cumulative incidence of Grade 2 or higher genitourinary (GU) and gastrointestinal (GI) toxicity was 62% and 12% in the single-fraction arm, and 47% and 9% in the two-fraction arm, respectively. Grade 3 GU toxicity was only seen in the single fraction arm with a cumulative incidence of 2%. The 5-year prevalence of Grade 2 GU toxicity was 29% and 21%, in the single- and two-fraction arms, respectively, with Grade 2 GI toxicity of 1% and 2%. Beyond the first year, no significant differences in mean urinary HRQOL were seen compared to baseline in the two-fraction arm, in contrast to the single-fraction arm where a decline in urinary HRQOL was seen at 4 and 5 years. Sexual HRQOL was significantly reduced in both treatment arms at all timepoints, with no changes in the bowel domain. CONCLUSIONS: HDR monotherapy is well tolerated with minimal impact on HRQOL.

A Novel Salvage Option for Local Failure in Prostate Cancer, Reirradiation Using External Beam or Stereotactic Radiation Therapy: Systematic Review and Meta-Analysis.

PURPOSE: Reirradiation (re-RT) using external beam radiation therapy (EBRT) is a novel salvage strategy for local failure in prostate cancer. We performed a systematic review describing oncologic and toxicity outcomes for salvage EBRT/stereotactic radiation therapy (SBRT) re-RT. METHODS AND MATERIALS: A International Prospective Register of Systematic Reviews registered (#141466) systematic review, meta-analysis, and meta-regression was conducted using preferred reporting items for systematic reviews and meta-analyses guidelines. PubMed and EMBASE were searched from inception through September 2019. Outcome measures included local control (LC), biochemical relapse free survival (BRFS), and ≥grade 3 genitourinary (GU)/gastrointestinal (GI) toxicity. EBRT and SBRT data were collected separately. Meta-regression explored disease and toxicity outcomes as a function of equivalent dose in 2 Gy fractions (EQD2), length of follow-up, and partial versus whole prostate reirradiation. RESULTS: Nineteen studies representing 13 cohorts were included (428 patients). Weighted mean follow-up was 26.1 months. Median re-RT EQD2 was 77.1 Gy (α/ß = 1.5), with 92% of patients receiving SBRT, 52.1% of patients receiving partial prostate re-RT, and 30.1% of patients receiving androgen deprivation therapy with re-RT. LC was 83.2% (95% confidence interval [CI], 75.5%-90.9%) and BRFS was 59.3% (47.9%-70.7%). Reported late toxicity ≥grade 3 was 3.4% (95% CI, 1.0%-5.8%) for GU and 2.0% (95% CI, 0.1%-4.0%) for GI. Meta-regression found higher LC, BRFS, and reported GU/GI toxicity with increasing EQD2, with partial prostate re-RT associated with less reported GU/GI toxicity and no detriment to LC and BRFS. CONCLUSIONS: Salvage re-RT using EBRT, particularly with SBRT, is an emerging technique to treat isolated local failure of prostate cancer. With short-term follow-up, LC, BRFS, and reported toxicities appear reasonable, although further follow-up is required before definitive statements on late toxicities can be made. Our review is limited by incomplete reporting of androgen deprivation therapy use in the primary literature. Further prospective studies and longer follow-up are needed before considering re-RT as standard practice.

Is prostate brachytherapy a dying art? Trends and variation in the definitive management of prostate cancer in Ontario, Canada.

BACKGROUND AND PURPOSE: Declining prostate brachytherapy utilization has been reported in several studies, despite strong evidence for efficacy and safety compared to alternatives. We sought to evaluate contemporary trends in brachytherapy, external beam radiotherapy (EBRT) and prostatectomy utilization in a publicly funded healthcare system. MATERIALS AND METHODS: Men with localized prostate cancer diagnosed and treated between 2006 and 2017 in Ontario, Canada were identified using administrative data. Men received EBRT, brachytherapy (monotherapy or boost) or prostatectomy as initial definitive management. Multivariable logistic regression evaluated patient-, tumour-, and provider-factors on treatment utilization. RESULTS: 61,288 men were included. On multivariable regression, the odds of receiving brachytherapy boost increased 24% per year (odds ratio [OR]:1.24, 95% CI 1.22-1.26, p < 0.01), brachytherapy monotherapy increased 3% per year (OR:1.03, 95% CI:1.02-1.04, p < 0.01), and prostatectomy declined by 6% per year (OR:0.94, 95% CI 0.93-0.95, p < 0.01). Treatment year was not significant on multivariable modelling of EBRT. In a separate multivariable model limited to those who received radiotherapy, if the first radiation oncologist seen performed brachytherapy, the OR of receiving brachytherapy monotherapy over EBRT was 5.66 (95% CI: 5.11-6.26, p < 0.01) and 2.88 (95% CI: 2.60-3.19, p < 0.01) for brachytherapy boost over EBRT alone. Substantial geographic, provider and patient variation in treatment receipt was observed. CONCLUSION: We found increasing brachytherapy utilization, largely driven by increasing utilization of brachytherapy boost. To our knowledge, this is the first report of increasing brachytherapy use in the era of dose escalated EBRT.

Does 5 + 5 Equal Better Radiation Treatment Plans in Head and Neck Cancers?

PURPOSE: Accurate contouring in head and neck cancer (HNC) is critical. International consensus guidelines recommend the 5 + 5 mm rule for expansions around the primary tumor, wherein high- and low-dose clinical target volumes (CTV-P1 and CTV-P2, respectively) are created using successive 5 mm expansions on the gross tumor volume. To our knowledge, the necessity of a low-dose CTV-P2 has never been assessed; therefore, we evaluated the dosimetric impact of adding a CTV-P2 expansion using the 5 + 5 mm rule compared with contouring with a high-dose CTV-P1 alone. METHODS AND MATERIALS: A retrospective study of clinically delivered (chemo)radiation therapy treatment plans for HNC was conducted. All patients were treated with 70 Gy in 35 fractions using volumetric modulated arc therapy in a single phase. CTV-P2 was retrospectively contoured per guidelines as a 5 mm expansion on CTV-P1 from the clinical plan, carving off specified barriers to spread. We used a 5 mm planning target volume (PTV) expansion. Our primary outcome was whether 95% of the volume of the PTV for the CTV-P2 contour (ie, PTV-P2) received at least 56 Gy. To assess dose falloff, the coverage of a PTV ring structure was created by subtracting PTV-P1 from PTV-P2. RESULTS: Twenty-seven patients from 4 HNC subsites (base of tongue, tonsil, hypopharynx, and supraglottic larynx) were included. In all 108 treatment plans, at least 95% of the PTV-P2 structure received at least 56 Gy. The minimum volume of the PTV-P2 structure receiving at least 56 Gy was 97.4%. Eight of 108 treatment plans had borderline coverage of the PTV ring substructure alone. CONCLUSIONS: Adding a CTV-P2 structure using the 5 + 5 mm rule had no dosimetric impact, adds contouring time, adds treatment planning complexity, and could potentially introduce errors. The 5 + 5 mm rule may have value in other settings, such as when smaller PTV margins are used, and warrants further evaluation with prospective or randomized studies.

Radical radiotherapy for locally advanced non-small cell lung cancer-what's up with arm positioning?

Radical thoracic radiotherapy is ideally delivered in the arms-up (AU) position; however, patient comfort may only allow for arms-down (AD) positioning to be feasible. Objectives of this study were (I) to evaluate the dosimetric impact of changing arm position during treatment and (II) to compare plan quality for optimization in AU vs. AD positions. In this retrospective planning study, stage III lung cancer patients (n=10) who received 60 Gy in 30 fractions using volumetric modulated arc therapy (VMAT) were identified. To simulate AD treatment, a PET/CT (acquired AD) was registered to the planning CT (acquired AU) for arm delineation. The clinically delivered plan (AU) was recalculated with a density override to 1 g/cm3 for one or both arm contours (AD). Plans were also re-optimized for the AD position. Dose-volume parameters were compared for each scenario. Moving from AU to AD without re-optimization resulted in a mean 3.7% reduction in PTV D95; in all cases, this caused 95% of the PTV to receive ≤57 Gy. The mean arms D2cc were 23.1 and 4.0 Gy for the ipsilateral and contralateral, respectively. Dosimetric consequences of ipsilateral arm only were similar to both AD, whereas contralateral arm only had less than 1% effect on PTV D95. Re-optimizing to account for both AD recovered PTV D95 coverage with acceptable doses to all organs at risk. Arm D2cc were also decreased to 5.5 and 2.3 Gy for ipsilateral and contralateral, respectively. There was a significant difference in heart V25 and mean heart dose (P<0.001), but the magnitude was small at 4.1% for V25 and 1.7 Gy for mean heart dose and the plans still met institutional dose constraints. This planning study suggests that it is feasible to plan radiotherapy for locally advanced lung cancer patients in the AD position using VMAT, when necessary, with only a modest dosimetric impact.

When Pap Testing Fails to Prevent Cervix Cancer: A Qualitative Study of the Experience of Screened Women Under 50 with Advanced Cervix Cancer in Canada.

INTRODUCTION: While Papanicolaou (Pap) smears have resulted in a significant decline in cervical cancer incidence and mortality, our clinical experience indicates some women still present with locally advanced cervical cancer (LACC) despite having received Pap smear screening. Recent guidelines have decreased the recommended frequency of Pap smears to every three years. Our study sought to investigate the experiences of young women compliant with cervical screening who presented with LACC. METHODS: Women under 50 with LACC, FIGO (International Federation of Gynecology and Obstetrics) stage IB1 to IVA who underwent a Pap smear within two years of diagnosis and received curative intent chemoradiotherapy between September 2010 and December 2012 were included. Participants were treated at a tertiary academic cancer centre and invited for a semi-structured, in-person interview, which was analysed qualitatively using thematic analysis. RESULTS: Thirteen out of 38 women had Pap screening two or less years before diagnosis. Ten consented to participate in an interview. Several key themes emerged: I) Belief that LACC does not occur in those who undergo screening; II) Lack of understanding about LACC symptoms/diagnosis of cervix cancer; III) Reluctance from health care providers to perform a detailed pelvic examination in the presence of symptoms; IV) Negative emotions including anger, shame, regret, mistrust; V) Changes in quality of life from treatment; VI) Advice for other women. CONCLUSIONS: One-third of women presenting with LACC had appropriate Pap screening prior to diagnosis. Patients believe delays in their diagnosis resulted in detrimental quality of life. There is a need to educate physicians and the public about the symptoms of cervix cancer and to consider this diagnosis even when Pap screening has occurred.