Estimation of Annual Secondary Lung Cancer Deaths Using Various Adjuvant Breast Radiotherapy Techniques for Early-Stage Cancers.

PURPOSE: Secondary lung cancer (SLC) can offset the benefit of adjuvant breast radiotherapy (RT), and risks compound sharply after 25 to 30 years. We hypothesized that SLC risk is mainly an issue for early-stage breast cancer, and that lives could be saved using different RT techniques. PATIENTS AND METHODS: The SEER database was used to extract breast patient age, stage survival, and radiotherapy utilization over time and per stage and to assess the factors associated with increased SLC risk with a multivariable competing risk Cox model. The number of SLC was calculated using the BEIR model modified with patient survival, age, and use of RT from the SEER database. Stage distribution and number of new breast cancer cases were obtained from the NAACCR. Mean lung dose for various irradiation techniques was obtained from measurement or literature. RESULTS: Out of the 765,697 non-metastatic breast cancers in the SEER database from 1988 to 2012, 49.8% received RT. RT significantly increased the SLC risk for longer follow-up (HR=1.58), early stage including DCIS, stage I and IIA (HR = 1.11), and younger age (HR=1.061) (all p<0.001). More advanced stages did not have significantly increased risk. In 2019, 104,743 early-stage breast patients received radiotherapy, and an estimated 3,413 will develop SLC (3.25%) leading to an excess of 2,900 deaths (2.77%). VMAT would reduce this mortality by 9.9%, hypofractionation 26 Gy in five fractions by 38.8%, a prone technique by 70.3%, 3D-CRT APBI by 43.3%, HDR brachytherapy by 71.1%, LDR by 80.7%, and robotic 4π APBI by 85.2%. CONCLUSIONS: SLC after breast RT remains a clinically significant issue for early-stage breast cancers. This mortality could be significantly reduced using a prone technique or APBI.

Improvement of consistency in delineating breast lumpectomy cavity using surgical clips.

BACKGROUND: Delineation of lumpectomy cavity for whole breast radiation therapy after breast conserving surgery can be challenging because of poor visualization of the cavity. The use of surgical clips on lumpectomy cavity walls has been suggested as an effective and low-cost method to improve the accuracy and consistency of lumpectomy cavity delineation. MATERIALS AND METHODS: Twenty-three eligible female breast cancer patients who were treated with lumpectomy and adjuvant radiation therapy were recruited for this study. During breast conserving surgery, four surgical clips were placed on the superior, inferior, lateral, and medial walls of the lumpectomy cavity. Patients were imaged prior and during radiation treatment. Software was developed to anonymize the image sets and digitally remove the clips from the computed tomography images. Three radiation oncologists contoured the lumpectomy cavity volume, with and without presence of clips. Contoured image sets were analyzed with regard to cavity volume, dimensions, and concordance index. Statistical analysis was performed using a paired t-test. RESULTS: The presence of clips significantly increased the average lumpectomy cavity volumes from 23.50 cc to 26.42 cc (P < 0.0001). The presence of clips also significantly increased the mean craniocaudal, anteroposterior, and mediolateral dimensions by 6.8, 2.3, and 2.9 mm, respectively (all P < 0.01). In addition, the presence of surgical clips improved the consistency in delineation in CC dimension by significantly decreasing the standard deviation (P < 0.006). CONCLUSIONS: The presence of surgical clips improves the accuracy of lumpectomy cavity delineation. However, consistency is only improved in CC dimension.

Long-term Outcomes and Late Effects of Definitive Chemoradiotherapy in Patients with Cervical Cancer in Nova Scotia.

PURPOSE:  To determine the long-term oncologic outcomes and toxicity of patients treated with definitive chemo-radiotherapy for cervical cancer.  METHODS AND MATERIALS:  The study period was January 1, 2000 to December 31, 2009. All patients diagnosed with cervical cancer who received curative-intent chemoradiotherapy were included. Patients were excluded if they resided out of the province, received surgery as an initial treatment, or were treated with palliative intent. A retrospective chart review was performed. RESULTS: Four hundred and eighty-six patients were diagnosed with cervical cancer; 190 met eligibility criteria. Median follow-up for all patients was 3.2 years (interquartile range 1.1-5.6 years). Clinical stage was FIGO IIB or higher in 139 of 190 patients (73.2%). One hundred and fifty-eight (82.7%) received concurrent cisplatin chemotherapy (mean # cycles = 4.8). The most common external beam radiotherapy (EBRT) dose/fractionation schedule was 45 Gray (Gy) in 25 fractions (149 pts, 78.0%). One hundred and thirty-six (71.2%) received low-dose-rate (LDR) brachytherapy (BT: most common dose = 35 Gy). High-dose-rate (HDR) BT was implemented in 2008; the most common HDR dose was 24 Gy in 8 fractions over five days.  Five-year overall survival (OS) and progression-free survival (PFS) were 69.4% and 61.4%, respectively. OS and PFS were significantly higher in patients who received chemotherapy vs. radiotherapy alone. For those receiving HDR-BT, there was a significantly higher OS, but not PFS. The rate of late RTOG Grade 3/4 toxicity at five years was 23.3% (gastrointestinal - 26 events, 13% of patients; genitourinary - 13 events, 8% of patients). Fourteen patients had Grade 3 radiation proctitis as the only late toxicity. EBRT dose above 45 Gy was the only factor associated with late toxicity on multivariate analysis. CONCLUSION:  Outcomes of patients treated with chemoradiotherapy for cervical cancer are in keeping with those reported in other series. Chemotherapy improved OS and PFS. External beam radiotherapy dose above 45 Gy was the only predictor of late toxicity.

Regional Nodal Irradiation in Early-Stage Breast Cancer.

BACKGROUND: Most women with breast cancer who undergo breast-conserving surgery receive whole-breast irradiation. We examined whether the addition of regional nodal irradiation to whole-breast irradiation improved outcomes. METHODS: We randomly assigned women with node-positive or high-risk node-negative breast cancer who were treated with breast-conserving surgery and adjuvant systemic therapy to undergo either whole-breast irradiation plus regional nodal irradiation (including internal mammary, supraclavicular, and axillary lymph nodes) (nodal-irradiation group) or whole-breast irradiation alone (control group). The primary outcome was overall survival. Secondary outcomes were disease-free survival, isolated locoregional disease-free survival, and distant disease-free survival. RESULTS: Between March 2000 and February 2007, a total of 1832 women were assigned to the nodal-irradiation group or the control group (916 women in each group). The median follow-up was 9.5 years. At the 10-year follow-up, there was no significant between-group difference in survival, with a rate of 82.8% in the nodal-irradiation group and 81.8% in the control group (hazard ratio, 0.91; 95% confidence interval [CI], 0.72 to 1.13; P=0.38). The rates of disease-free survival were 82.0% in the nodal-irradiation group and 77.0% in the control group (hazard ratio, 0.76; 95% CI, 0.61 to 0.94; P=0.01). Patients in the nodal-irradiation group had higher rates of grade 2 or greater acute pneumonitis (1.2% vs. 0.2%, P=0.01) and lymphedema (8.4% vs. 4.5%, P=0.001). CONCLUSIONS: Among women with node-positive or high-risk node-negative breast cancer, the addition of regional nodal irradiation to whole-breast irradiation did not improve overall survival but reduced the rate of breast-cancer recurrence. (Funded by the Canadian Cancer Society Research Institute and others; MA.20 ClinicalTrials.gov number, NCT00005957.).

Polymorphisms in cinnamoyl CoA reductase (CCR) are associated with variation in microfibril angle in Eucalyptus spp.

Linkage disequilibrium (LD) mapping using natural populations results in higher resolution of marker-trait associations compared to family-based quantitative trait locus (QTL) studies. Depending on the extent of LD, it is possible to identify alleles within candidate genes associated with a trait. Analysis of a natural mutant in Arabidopsis has shown that mutations in cinnamoyl CoA reductase (CCR), a key lignin gene, affect physical properties of the secondary cell wall such as stiffness and strength. Using this gene, we tested whether LD mapping could identify alleles associated with microfibril angle (MFA), a wood quality trait affecting stiffness and strength of wood. We identified 25 common single-nucleotide polymorphism (SNP) markers in the CCR gene in Eucalyptus nitens. Using single-marker and haplotype analyses in 290 trees from a E. nitens natural population, two haplotypes significantly associated with MFA were found. These results were confirmed in two full-sib families of E. nitens and Eucalyptus globulus. In an effort to understand the functional significance of the SNP markers, we sequenced the cDNA clones and identified an alternatively spliced variant from the significant haplotype region. This study demonstrates that LD mapping can be used to identify alleles associated with wood quality traits in natural populations of trees.

Radiotherapy wait times for patients with a diagnosis of invasive cancer, 1992-2000.

PURPOSE: To study the wait times for cancer patients from the time of diagnosis to consultation with a radiation oncologist (T1), from consultation to radiotherapy (T2) and from diagnosis to radiotherapy (T3) in the context of treatment practices and measurement issues. METHODS: From 1992 to 2000, we studied 6585 Nova Scotian patients over the age of 24 years with a diagnosis of breast, lung, colorectal or prostate cancer who received radiotherapy within 1 year of diagnosis. Multivariate analyses examined associations between wait time and diagnosis year, age, sex, median household income (MHI), distance to the cancer centre and extent of disease. Univariate findings reported are median times and interquartile ranges. RESULTS: The T3 was 16 weeks for breast and colorectal cancer, 6 weeks for lung cancer and 18 weeks for prostate cancer. The greatest T1 decrease over time was for prostate cancer: 13-8 weeks (hazards ratio [HR] = 1.07, 95% confidence interval [CI] = 1.05-1.10). The T2 increased for all cancers, and the T3 increased from 5 to 7 weeks for lung cancer, from 17 to 22 weeks for prostate cancer and from 10 to 18 weeks for breast cancer, with no change for colorectal cancer. The T3 decreased by age for breast cancer (HR = 1.12, CI = 1.10-1.14) and prostate cancer (HR = 1.07, CI = 1.02-1.11), showed no consistent association with distance to a cancer centre and varied by extent of disease. Patients with localized lung disease had a longer T3 than those with distant disease, but the opposite results were noted for patients with breast cancer. The T3 was greater for regional than distant disease in lung and breast cancers. Sex and MHI had no effect. CONCLUSION: Wait times reflected clinical practice, and there were no adverse patterns related to age, sex, income or distance from a cancer centre.