Abstract Aim To compare quality of life (QOL) between standard (SFX) chemoradiotherapy (arm A) and altered fractionation radiotherapy (AFX) with panitumumab (PMab; arm B). Methods Patients with T any ...N + M0 or T3-4N0M0 squamous cell head-neck carcinoma were randomised to SFX (70 Gy/35/7 wks) plus cisplatin (100 mg/m2 IV × 3) versus AFX (70 Gy/35/6 wks) plus PMab (9 mg/kg IV × 3). QOL was collected at baseline, end of radiation therapy (RT) and 2, 4, 6, 12, 24 and 36 months post-RT using the Functional Assessment of Cancer Therapy Head and Neck (FACT-H&N), MD Anderson Dysphagia Index (MDADI) and SWAL-QOL. We hypothesised a 6-point more favourable change in FACT-H&N score from baseline to 1 year in arm B over arm A. Results Among 320 patients, median follow-up was 46 (range: 0.1–64.3) months, median age 56, 84% male, Eastern Cooperative Oncology Group PS 0 (71%), 1 (29%). Primary site was oropharynx in 81% (p16+ 68%, p16− 16%, missing 16%). Baseline scores did not differ by arm (A/B): FACT-H&N 116.5/115, MDADI Global 83/77, SWAL-QOL General 67/68. At 1 year, no difference was seen between arms in FACT-H&N change from baseline: A −1.70, B −4.81, p = 0.194. Subscale change scores by arm were (A/B): last week RT, FACT-Physical (−11.6, −10, p = 0.049), MDADI Physical (−40.4, −33.9, p = 0.045), and SWAL-QOL Eating Duration (−61.2, −51.2, p = 0.02), Eating Desire (−53.3, −43.9, p = 0.031) and Mental Health (−42, −32.6, p = 0.009); 4 months, HN subscale (−7.7, −10, p = 0.014). No clinically important differences by arm were seen post-treatment. Conclusions PMab with AFX did not durably improve QOL or swallowing as compared with SFX with cisplatin. Trial registration ClinicalTrials.gov: NCT00820248.
Adjuvant trastuzumab has been associated with superior survival in women with ≥ T1c or node-positive HER2-positive early-stage breast cancer; however, there is a lack of phase III trials in women ...with T1a/bN0 disease. Our study aimed to assess the outcomes of women with HER2-positive T1a/bN0 breast cancer who received adjuvant trastuzumab in Saskatchewan, Canada. We evaluated all women diagnosed with HER2-positive T1a/bN0 breast cancer in Saskatchewan between 2008 and 2017. We performed Cox proportional multivariable analysis to determine factors correlated with survival. In addition, inverse probability treatment weighting (IPTW) using propensity score was performed to assess benefit of adjuvant trastuzumab. Ninety-one eligible women with a median age of 61 years (range 30-89) were identified. Thirty-nine (43%) women received adjuvant trastuzumab. Women who received trastuzumab were younger and had a higher rate of T1b disease. Overall, 3% of women who received trastuzumab compared to 12% of women who did not receive trastuzumab developed breast cancer recurrence (p = 0.23). Five-year disease-free survival (DFS) of women who received adjuvant trastuzumab was 94.8% compared to 82.7% of women who did not receive trastuzumab (p = 0.22). Five-year overall survival was 100% of women who received trastuzumab compared to 90.4% of women who did not receive adjuvant trastuzumab (p = 0.038). In the multivariable analysis, grade III tumors were correlated with inferior DFS (hazard ratio HR 5.5, 95% CI 1.7-17.7). The propensity score using the inverse probability of treatment weighting showed that lack of adjuvant trastuzumab was correlated inferior DFS, with an HR of 4 (95% CI 1.05-15.5). Women with HER2-positive T1a/bN0 breast cancer had overall low recurrence of breast cancer. However, the results of this exploratory analysis indicate that women who received adjuvant trastuzumab had better survival.
Fiducial markers and daily electronic portal imaging (EPI) can reduce the risk of geographic miss in prostate cancer radiotherapy. The purpose of this study was to estimate CTV to PTV margin ...requirements, without and with the use of this image guidance strategy.
46 patients underwent placement of 3 radio-opaque fiducial markers prior to prostate RT. Daily pre-treatment EPIs were taken, and isocenter placement errors were corrected if they were > or = 3 mm along the left-right or superior-inferior axes, and/or > or = 2 mm along the anterior-posterior axis. During-treatment EPIs were then obtained to estimate intra-fraction motion.
Without image guidance, margins of 0.57 cm, 0.79 cm and 0.77 cm, along the left-right, superior-inferior and anterior-posterior axes respectively, are required to give 95% probability of complete CTV coverage each day. With the above image guidance strategy, these margins can be reduced to 0.36 cm, 0.37 cm and 0.37 cm respectively. Correction of all isocenter placement errors, regardless of size, would permit minimal additional reduction in margins.
Image guidance, using implanted fiducial markers and daily EPI, permits the use of narrower PTV margins without compromising coverage of the target, in the radiotherapy of prostate cancer.
Introduction: Fulvestrant has demonstrated efficacy in hormone receptor positive (HR+) metastatic breast cancer (mBC), both in first-and second-line settings. In clinical practice, however, ...fulvestrant has been used as a later-line therapy. This study assessed the efficacy of fulvestrant in women with mBC in early-versus later-line therapy. Methods: This retrospective cohort study assessed Saskatchewan women with HR+ mBC who received fulvestrant between 2003–2019. A multivariate Cox proportional survival analysis was performed. Results: One hundred and eighty-six women with a median age of 63.5 years were identified—178 (95.6%) had hormone-resistant mBC, 57.5% had visceral disease, and 43.0% had received chemotherapy before fulvestrant. 102 (54.8%) women received ≤2-line-therapy, and 84 (45.2%) received ≥3 line-therapy before fulvestrant. The median time to progression (TTP) was 12 months in the early-treatment vs. 6 months in the later-treatment group, p = 0.015. Overall survival (OS) from the start of fulvestrant was 26 months in the early-treatment group vs. 16 months in the later-treatment group, p = 0.067. On multivariate analysis, absence of visceral metastasis, HR: 0.70 (0.50–0.99), was significantly correlated with better TTP, whereas post-fulvestrant chemotherapy, HR: 0.32 (0.23–0.47), clinical benefit from fulvestrant, HR: 0.44 (0.30–0.65), and absence of visceral metastasis, HR: 0.70 (0.50–0.97), were correlated with better OS. Conclusions: Fulvestrant has demonstrated efficacy as both early-and later-line therapy in hormone-resistant mBC. Our results show that women with clinical benefit from fulvestrant, who received post-fulvestrant chemotherapy, or had non-visceral disease, had better survival.
Breast cancer is rare in men. This population-based study aimed to determine outcomes of male breast cancer in relation to residence and other variables.
In this retrospective cohort study, men ...diagnosed with breast cancer in Saskatchewan during 2000-2019 were evaluated. Cox proportional multivariable regression analyses were performed to determine the correlation between survival and clinicopathological and contextual factors.
One hundred-eight eligible patients with a median age of 69 years were identified. Of them, 16% had WHO performance status ≥ 2 and 61% were rural residents. The stage at diagnosis was as follows: stage 0, 7%; I, 31%; II, 42%; III, 11%; IV, 8%. Ninety-eight percent had hormone receptor-positive breast cancer. The median disease-free survival of urban patients was 97 (95% CI: 50-143) vs. 64 (46-82) months of rural patients (
= 0.29). The median OS of urban patients was 127 (94-159) vs. 93 (32-153) months for rural patients (
= 0.27). On multivariable analysis, performance status ≥ 2, hazard ratio (HR) 2.82 (1.14-6.94), lack of adjuvant systemic therapy, HR 2.47 (1.03-5.92), and node-positive disease, HR 2.32 (1.22-4.40) were significantly correlated with inferior disease-free survival in early-stage invasive breast cancer. Whereas stage IV disease, HR 7.8 (3.1-19.5), performance status ≥ 2, HR 3.25 (1.57-6.71), and age ≥ 65 years, HR 2.37 (1.13-5.0) were correlated with inferior overall survival in all stages.
Although residence was not significantly correlated with outcomes, rural men had numerically inferior survival. Poor performance status, node-positive disease, and lack of adjuvant systemic therapy were correlated with inferior disease-free survival.
: Nodal ratio (NR) is defined as the number of involved nodes to the number of nodes examined. There is limited information on the application of NR on population data. Previous reports in breast ...cancer generally analyzed one to three positive axillary nodes as a single group. This study investigates whether one to three positive axillary nodes is a homogeneous group in prognosis by comparing one to two positive nodes to three positive nodes. The population‐based registry of a Canadian province from 1981 through 1995 was searched. As the reliability of nodal assessment depends on the number of nodes sampled, we also studied the subgroup of patients with greater than or equal to eight nodes dissected. Of a total of 5,996 breast cancer patients, 1187 had one to three positive axillary nodes. The 263 patients with three positive nodes compared to the 924 patients with one to two nodes fared worse with a significantly reduced cause‐specific survival (CSS) and overall survival (OS). Patients with one to two positive nodes had similar CSS (p = 0.31) and OS (p = 0.63). Among those with greater than or equal to eight nodes dissected, there were 677 patients with one to two positive nodes. CSS and OS were not significantly different between one versus two positive nodes (p = 0.16 and 0.34, respectively), but with NR, the corresponding p values were 0.0068 and 0.08, respectively. The cutoff value of NR 0.15 was found to be most useful and confirmed by the validation dataset. NR is able to segregate patients better than the absolute number of positive nodes used in the current staging system. NR should be incorporated into the staging system.
It remains unknown whether or not short-term androgen deprivation (STAD) improves survival among men with intermediate-risk prostate cancer (IRPC) treated with dose-escalated radiotherapy (RT).
The ...NRG Oncology/Radiation Therapy Oncology Group 0815 study randomly assigned 1,492 patients with stage T2b-T2c, Gleason score 7, or prostate-specific antigen (PSA) value >10 and ≤20 ng/mL to dose-escalated RT alone (arm 1) or with STAD (arm 2). STAD was 6 months of luteinizing hormone-releasing hormone agonist/antagonist therapy plus antiandrogen. RT modalities were external-beam RT alone to 79.2 Gy or external beam (45 Gy) with brachytherapy boost. The primary end point was overall survival (OS). Secondary end points included prostate cancer-specific mortality (PCSM), non-PCSM, distant metastases (DMs), PSA failure, and rates of salvage therapy.
Median follow-up was 6.3 years. Two hundred nineteen deaths occurred, 119 in arm 1 and 100 in arm 2. Five-year OS estimates were 90% versus 91%, respectively (hazard ratio HR, 0.85; 95% CI, 0.65 to 1.11;
= .22). STAD resulted in reduced PSA failure (HR, 0.52;
<.001), DM (HR, 0.25;
<.001), PCSM (HR, 0.10;
= .007), and salvage therapy use (HR, 0.62;
= .025). Other-cause deaths were not significantly different (
= .56). Acute grade ≥3 adverse events (AEs) occurred in 2% of patients in arm 1 and in 12% for arm 2 (
<.001). Cumulative incidence of late grade ≥3 AEs was 14% in arm 1 and 15% in arm 2 (
= .29).
STAD did not improve OS rates for men with IRPC treated with dose-escalated RT. Improvements in metastases rates, prostate cancer deaths, and PSA failures should be weighed against the risk of adverse events and the impact of STAD on quality of life.
To estimate the late morbidity of a novel, hypofractionated external beam radiotherapy schedule of 55Gy in 16 fractions (4 fractions/week, 3.4Gy per fraction) for localized prostate cancer.
A ...multi-center phase 2 study enrolled seventy-three patients between September 2004 and June 2006. After insertion of fiducial gold markers, they were treated with image-guidance (IGRT) using conformal techniques with intensity-modulation, if necessary, and then followed every 6months for toxicity rating and PSA. Patient reported outcomes were collected yearly. Median follow up was 4.6years.
At 4years post-radiotherapy, the cumulative incidence of combined urinary and bowel grade 3 toxicity was 7% (95% CI 3–16%) and grade 2+ was 33% (95% CI 24–46%). All except two patients recovered from their grade 3 events. Patient-reported reduction of function was most pronounced at year two for urinary function (mean −7, SD 16), and at year one for bowel function (mean −7, SD 21). The cumulative incidence of biochemical (PSA nadir+2) or biopsy-proven relapse at 4years was 9% (95% CI 4–18%).
Hypofractionated radiotherapy is clinically feasible and more convenient than conventional schedules for patients with localized prostate cancer. Phase 3 multicenter studies are on-going (NCT00126165).
To develop multi-institutional consensus clinical target volumes (CTVs) and organs at risk (OARs) for male and female bladder cancer patients undergoing adjuvant radiation therapy (RT) in clinical ...trials.
We convened a multidisciplinary group of bladder cancer specialists from 15 centers and 5 countries. Six radiation oncologists and 7 urologists participated in the development of the initial contours. The group proposed initial language for the CTVs and OARs, and each radiation oncologist contoured them on computed tomography scans of a male and female cystectomy patient with input from ≥1 urologist. On the basis of the initial contouring, the group updated its CTV and OAR descriptions. The cystectomy bed, the area of greatest controversy, was contoured by another 6 radiation oncologists, and the cystectomy bed contouring language was again updated. To determine whether the revised language produced consistent contours, CTVs and OARs were redrawn by 6 additional radiation oncologists. We evaluated their contours for level of agreement using the Landis-Koch interpretation of the κ statistic.
The group proposed that patients at elevated risk for local-regional failure with negative margins should be treated to the pelvic nodes alone (internal/external iliac, distal common iliac, obturator, and presacral), whereas patients with positive margins should be treated to the pelvic nodes and cystectomy bed. Proposed OARs included the rectum, bowel space, bone marrow, and urinary diversion. Consensus language describing the CTVs and OARs was developed and externally validated. The revised instructions were found to produce consistent contours.
Consensus descriptions of CTVs and OARs were successfully developed and can be used in clinical trials of adjuvant radiation therapy for bladder cancer.
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