Possible protective effect of rosuvastatin in chemotherapy-induced cardiotoxicity in HER2 positive breast cancer patients: a randomized controlled trial.

Cardiotoxicity is a side effect of chemotherapy in human epidermal growth factor receptor 2 (HER2) positive breast cancer patients receiving both anthracyclines and trastuzumab. We looked for a possible protective effect of rosuvastatin against chemotherapy-induced cardiotoxicity. Methods: 50 newly diagnosed HER2 positive breast cancer patients were randomly allocated into two groups: 25patients in each. Group 1(control group) received doxorubicin for 4 cycles (3 months) followed by trastuzumab adjuvant therapy. Group 2 (treatment group) received doxorubicin for 4 cycles (3 months) followed by trastuzumab adjuvant therapy and 20 mg of oral rosuvastatin 24 h before the first cycle of chemotherapy and once daily for the rest of the follow-up period (6 months). Transthoracic echocardiography was done, and blood samples were collected for patients 24 h before the initiation of therapy, after 3 months and after 6 months to assess serum levels of high sensitivity cardiac troponin I (hs-cTnI), Myeloperoxidase (MPO), Interleukin-6 (IL-6) and Alanine aminotransferase (ALT). The study was retrospectively registered in Clinical Trials.gov in April 2022. Its ID is NCT05338723. Compared to control group, Rosuvastatin-treated group had a significantly lower decline in LVEF after 3 months and after 6 months. They had significantly lower Hs-cTnI and IL-6 after 3 months and after 6 months, and significantly lower MPO after 6 months. Four patients in control group experienced cardiotoxicity while no one in rosuvastatin-treated group. Rosuvastatin attenuated cardiotoxicity, so it is a promising protective agent against chemotherapy-induced cardiotoxicity.

Rs12039395 Variant Influences the Expression of hsa-miR-181a-5p and PTEN Toward Colorectal Cancer Risk.

BACKGROUND: Single nucleotide polymorphisms (SNPs) in microRNA (miRNA) genes could alter miRNA expression levels or processing and, thus, may contribute to colorectal cancer (CRC) development. Therefore, this study aimed to examine whether the MIR181A1 genomic sequence possesses SNPs that can affect the expression of hsa-miR-181a-5p and, subsequently, impact its targets and associate with CRC risk. METHODS: The NCBI dbSNP database was searched for possible SNPs associated with MIR181A1. One SNP with a minor allele frequency > 5%, rs12039395 G > T was identified. In silico analyses determined the effect of the SNP on the secondary structure of the miRNA and predicted the hsa-miR-181a-5p target genes. The SNP was genotyped using allelic discrimination assay, the relative hsa-miR-181a-5p expression level was determined using quantitative real-time PCR, and immunohistochemical staining was used to detect target genes in 192 paraffin-embedded specimens collected from 160 CRC patients and 32 healthy subjects. RESULTS: The rs6505162 SNP conferred protection against CRC, and the G-allele presence provides may provide accessibility for the transcriptional machinery. Hsa-miR-181a-5p was significantly over-expressed in the CRC group compared to controls and in samples carrying the G-allele compared to those with T-allele. PTEN, identified as the only hsa-miR-181a-5p target implicated in CRC, was significantly diminished in the CRC group compared to controls and showed an inverse relationship with hsa-miR-181a-5p expression level as well as negatively associated with the G-allele presence in CRC. CONCLUSION: This study highlights that rs12039395 G > T may protect against CRC by influencing the expression of hsa-mir-181a-5p and its target gene, PTEN.

Celecoxib as an adjuvant to chemotherapy for patients with metastatic colorectal cancer: A randomized controlled clinical study.

OBJECTIVES: To investigate the anti-tumor activity and tolerability of celecoxib as an adjuvant therapy for patients with metastatic colorectal cancer (CRC). METHODS: In this randomized controlled study, 54 patients with metastatic CRC were randomized into 2 groups; the control group (n=28) which received 6 cycles of folinic acid, fluorouracil and irinotecan (FOLFIRI) regimen (5-flourouracil, leucovorin, irinotecan), and the celecoxib group (n=26) which received 6 cycles of FOLFIRI regimen plus celecoxib 200 mg twice daily. The study duration was 3 months. Patients were assessed at baseline and at the end of intervention through the Response Evaluation Criteria in Solid Tumors objective response rate (ORR) and through evaluating the serum concentrations of vascular endothelial growth factor (VEGF), soluble factor-related apoptosis (sFAS), sFAS ligand (sFASL), and epithelial neutrophil-activating peptide -78 (ENA-78/CXCL5). Common Terminology Criteria for Adverse Events version 6.0 was used for evaluating drug-related toxicity. RESULTS: After intervention, celecoxib/FOLFIRI arm showed significant elevation in ORR as compared to FOLFIRI arm (p=0.001). As compared to FOLFIRI arm, celecoxib/FOLFIRI arm showed significantly lower VEGF (p<0.001), CXCL5 (p<0.001), and sFASL (p<0.001) serum levels and significantly higher sFAS serum level and sFAS/FASL ratio (p<0.001). Furthermore, celecoxib/FOLFIRI arm showed significantly higher progression-free survival and one-year overall survival when compared to FOLFIRI arm. CONCLUSION: Celecoxib plus chemotherapy may represent an effective and safe synergetic protocol for patients with metastatic CRC.Clinicaltrial.gov ID:NCT03645187.

Evaluation of radiation-induced cardiac toxicity in breast cancer patients treated with Trastuzumab-based chemotherapy.

PURPOSE: Patients with Her2-positive breast cancer treated with trastuzumab have higher rates of cardiotoxicity (CT). Left-breast radiation might increase the risk for CT from cardiac exposure to radiation. The goal of our study is to evaluate the contribution of radiotherapy (RT) in the development of CT in breast cancer patients receiving trastuzumab. METHODS: Two hundred and two patients were treated with RT and trastuzumab from 2000 to 2014. The RT plans for left-side disease were recalled from archives. The heart, each chamber, and left anterior descending artery (LAD) were independently contoured. New dose-volume histograms (DVH) were generated. Their serial left-ventricular ejection fractions (LVEF) were studied. CT for left and right side were compared using Fisher's exact test. The DVH data were correlated with the predefined cardiac events using actuarial Cox regression analysis. RESULTS: Compared to the right sided, the left-side cases showed statistically significant development of arrhythmia (14.2%) versus (< 1%) (p < 0.001). Cardiac ischemia was found in 10 patients in left and one patient in right side (p = 0.011). The equivalent uniform dose (EUD) to the left ventricle (LV), right ventricle (RV), and LAD was significantly associated with decrease in LVEF by > 10% (p = 0.037, p = 0.023 and p = 0.049, respectively). CONCLUSIONS: Among patients treated for left-sided lesions, there were no significant differences in EF decline. However, there was a higher rate of ischemia and arrhythmia compared to those with right-sided disease. The EUD index of LV, RV, and LAD could be considered as a parameter to describe the risk of radiation-induced CT.

Predictive factors of overall quality of life in advanced cancer patients using EORTC QLQ-C30.

OBJECTIVE: To identify which domains/symptoms from the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) were predictive of overall quality of life (QoL) in advanced cancer patients. METHODS: Four hundred and forty seven patients with brain metastases or bone metastases from seven countries were enrolled with regression analysis to determine the predictive value of the QLQ-C30 functional/symptom scores for patient reported overall QoL (question 30), overall health (question 29) and the global health status domain (questions 29 and 30). RESULTS: Worse role functioning, social functioning, fatigue and financial problems were the most significant predictive factors for worse QoL. In the bone metastases subgroup (n = 400), role functioning, fatigue and financial problems were the most significant predictors. In patients with brain metastases (n = 47), none of the EORTC domains significantly predicted worse QOL. CONCLUSION: Deterioration of certain QLQ-C30 functional/symptom scores significantly contributes to worse QoL, overall health and global health status.

Factors influencing health related quality of life in cancer patients with bone metastases.

OBJECTIVE: Health related quality of life (HRQOL) is a multidimensional concept that is especially important for cancer patients with bone metastases, as maintaining and improving HRQOL is often the main focus of treatment. This study aims to determine factors that may influence HRQOL, which may in turn influence treatment and care of patients. METHODS: Patients (n=396) completed the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) Bone Metastases module (BM22) at baseline. The EORTC QLQ-BM22 consists of four scales: painful site (PS), pain characteristics (PC), functional interference (FI), and psychosocial aspect (PA) scales. EORTC QLQ-BM22 data, together with sociodemographic and medical factors were analyzed by univariate analysis of variance (ANOVA). Items of significance were determined through backward selection, which were then put through multivariate analysis to determine further significance. RESULTS: Through ANOVA analysis, KPS>80 and breast primary histology were predictive of better HRQOL in the PS scale, while KPS>80, female gender, and breast primary histology were predictive of better HRQOL in the PC and FI scales. KPS>80 and prostate primary histology were predictive of better HRQOL in the PA scale. KPS>80 and primary cancer site were confirmed as significant predictive factors in multivariate analysis. RECOMMENDATIONS: This study identified baseline factors of gender, performance status, and primary histology as determinants of HRQOL in patients with bone metastases. Further study focusing on current treatment (chemotherapy, bisphosphonates, and radiotherapy) and spiritual well-being may identify additional factors affecting HRQOL. Understanding the influence of these factors will allow health care professionals to provide more effective palliative care.

Significance of autotaxin activity and overexpression in comparison to soluble intercellular adhesion molecule in thyroid cancer.

BACKGROUND: The objective of this study was to evaluate the role of autotaxin (ATX) activity and gene expression compared to soluble intercellular adhesion molecule-1 (sICAM-1) in thyroid carcinoma.
 PATIENTS AND METHODS: Sixty-five patients with thyroid swelling were included. There were 20 cases of simple multinodular goiter (group I), 15 cases of follicular adenoma (group II) and 30 cases of thyroid cancer (group III). Group III was further subdivided into negative and positive lymph nodes (group IIIa and IIIb; 22 and 8 cases, respectively). sICAM-1 concentration and ATX activity were measured using colorimetric enzyme-linked immunosorbent assay (ELISA), while ATX gene expression was detected by real-time polymerase chain reaction (PCR).
 RESULTS: sICAM-1 level, ATX activity and gene expression were significantly elevated in patients with thyroid carcinoma compared to other groups. The ATX activity showed significantly higher sensitivity and specificity than sICAM-1 (100% and 97.1% vs 93.3% and 88.6%, respectively). Both sICAM-1 and ATX values were significantly higher in patients with positive lymph nodes compared to those without lymph node involvement (p<0.001). Higher levels of ATX activity and gene expression were significantly correlated with larger tumor size and undifferentiated pathological subtype in thyroid carcinoma. In this respect, ATX was superior to sICAM-1.
 CONCLUSION: Our data suggest that ATX activity and gene expression are reliable diagnostic and prognostic tools in thyroid carcinoma compared to sICAM-1.

Predictive factors of overall well-being using the EORTC QLQ-C15-PAL extracted from the EORTC QLQ-C30.

OBJECTIVE: The European Organization of Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 15 Palliative (EORTC QLQ-C15-PAL) was developed to assess quality of life (QOL) for the palliative cancer population to decrease patient burden. The purpose of this study was to compare predictive factors for well-being in the QLQ-C15-PAL extracted from the EORTC Quality of Life Questionnaire - Core 30 (QLQ-C30) with the QLQ-C30 itself. METHODS AND MATERIALS: Patients with advanced cancer referred for treatment of bone metastases completed the QLQ-C30. Fifteen items from the QLQ-C15-PAL were extracted from the QLQ-C30. Univariate and multivariate analyses were used to determine predictive factors of the global QOL/health score in both tools. In the multivariate analyses, a p value of <0.003 indicated statistical significance. RESULTS: Overall, predictive factors were similar when analyzing data from both tools. Predictive factors for the QLQ-C30 were role functioning (p<0.0001), fatigue (p<0.0001), nausea/vomiting (p<0.0001), and financial problems (p<0.0001) and factors for the extracted QLQ-C15-PAL were physical functioning (p<0.0001) and fatigue (p<0.0001). CONCLUSIONS: Extraction of the QLQ-C15-PAL items from the QLQ-C30 resulted in similar predictive QOL domains for all patient subgroups analyzed individually. The QLQ-C15-PAL is reflective of the QLQ-C30 domains and is recommended for future studies involving patients in a palliative setting, as this shorter questionnaire reduces patient burden and may increase accrual and compliance, while maintaining a similar breadth of coverage and achieving the same predictive ability.

Quality of life after palliative radiation therapy for patients with painful bone metastases: results of an international study validating the EORTC QLQ-BM22.

PURPOSE: Radiation therapy (RT) is an effective method of palliating painful bone metastases and can improve function and reduce analgesic requirements. In advanced cancer patients, quality of life (QOL) is the primary outcome of interest over traditional endpoints such as survival. The purpose of our study was to compare bone metastasis-specific QOL scores among patients who responded differently to palliative RT. METHODS AND MATERIALS: Patients receiving RT for bone metastases across 6 countries were prospectively enrolled from March 2010-January 2011 in a trial validating the QLQ-BM22 and completed the QLQ-BM22 and the core measure (QLQ-C30) at baseline and after 1 month. Pain scores and analgesic intake were recorded, and response to RT was determined according to the latest published guidelines. The Kruskal-Wallis nonparametric and Wilcoxon rank sum tests compared changes in QOL among response groups. A Bonferroni-adjusted P<.003 indicated statistical significance. RESULTS: Of 79 patients who received palliative RT, 59 were assessable. Partial response, pain progression, and indeterminate response were observed in 22, 8, and 29 patients, respectively; there were no patients with a complete response. Patients across all groups had similar baseline QOL scores apart from physical functioning (patients who progressed had better initial functioning). One month after RT, patients who responded had significant improvements in 3 of 4 QLQ-BM22 domains (painful site, P<.0001; painful characteristic, P<.0001; and functional interference, P<.0001) and 3 QLQ-C30 domains (physical functioning, P=.0006; role functioning, P=.0026; and pain, P<.0001). Patients with progression in pain had significantly worse functional interference (P=.0007) and pain (P=.0019). CONCLUSIONS: Patients who report pain relief after palliative RT also have better QOL with respect to bone metastasis-specific issues. The QLQ-BM22 and QLQ-C30 are able to discriminate among patients with varying responses and are recommended for use in future bone metastasis clinical trials.

An international prospective study establishing minimal clinically important differences in the EORTC QLQ-BM22 and QLQ-C30 in cancer patients with bone metastases.

PURPOSE: Quality of life (QOL) is frequently an endpoint in clinical trials involving patients with advanced cancer. Statistical significance of minimal differences can be achieved with sufficient sample size, yet the actual clinical relevance is unknown. The purpose of this study was to establish the minimal clinically important difference (MCID) for the European Organisation for Research and Treatment of Cancer (EORTC) bone metastases module (EORTC QLQ-BM22). METHODS: Patients with bone metastases across seven countries were prospectively enrolled in a trial validating the EORTC QLQ-BM22 and completed the QLQ-BM22 and core measure (QLQ-C30) at baseline and 1-month follow-up. MCIDs were calculated for each QOL scale for both improvement and deterioration using both an anchor- (performance status) and distribution-based approach. RESULTS: A total of 93 patients completed both baseline and follow-up QOL and had recorded performance status at both intervals. Statistically significant meaningful differences were seen in seven scales. There were improvements of 30.5 (95 % confidence interval, 9.0 to 52.0), 20.1 (7.1 to 33.2), 30.5 (13.8 to 47.3) and 19.6 (5.0 to 34.3) in the pain, painful site, painful characteristic and functional interference scales, respectively, demonstrated clinical relevance. Decreases of 12.4 (0.3 to 24.6), 22.4 (11.8 to 32.9) and 13.5 (1.9 to 25.1) were required to represent clinically relevant deterioration in emotional functioning, global health status and financial issues, respectively. Minimal differences for improvement were closest to 0.5 standard deviations (SD) while for deterioration, closer to 0.3 SD on the QLQ-BM22. CONCLUSION: Identification of requirements for clinical significance can assist in determining the relevance of QOL changes after treatment and in sample size determination in future trials. Our study is limited by the small sample size. Future studies should continue to determine MCID and confirm our findings using a variety of appropriate anchors and in a larger sample.

Cytokeratin-19 fragments, nucleosomes and neuron-specific enolase as early measures of chemotherapy response in non-small cell lung cancer.

AIM: To investigate the reduction in the serum level of cytokeratin-19 fragments (CYFRA 21-1), nucleosomes and neuron-specific enolase (NSE) as early measures of the response to chemotherapy in non-small cell lung cancer (NSCLC). METHODS: Forty-two consecutive patients with locally advanced NSCLC were included. All patients received platinum-based chemotherapy. Staging investigations and quantification of CYFRA 21-1, nucleosomes and NSE (using enzyme-linked immunosorbent assay, ELISA) were performed before the start of treatment and after the second cycle of chemotherapy. According to the response to chemotherapy, patients were classified into 3 groups: (I) disease regression, (II) stable disease, and (III) progressive disease. The reduction in the levels of tumor markers was correlated with the response to chemotherapy. RESULTS: After the second cycle of chemotherapy, groups I and II had significantly decreased serum levels of CYFRA 21-1 (p<0.05). Similarly, the concentration of nucleosomes was significantly lower than the baseline levels in groups I (p=0.0008) and II (p=0.003). The reduction of both CYFRA 21-1 and nucleosome levels was not significant for patients in group III. In all groups the reduction of NSE levels in response to chemotherapy was not significant. As a marker of response to chemotherapy, CYFRA 21-1 showed the highest sensitivity (88.9%) and specificity (77.4%) compared with nucleosomes (77.8% and 58.1% respectively) and NSE (66.7% and 51.8% respectively). CONCLUSION: The reduction in the serum level of CYFRA 21-1 and nucleosomes may be used for early identification of NSCLC patients with good response to chemotherapy.

The role of chemokine CC ligand 20 in patients with liver cirrhosis and hepatocellular carcinoma.

BACKGROUND AND AIM: To evaluate the role of chemokine CC ligand 20 (CCL20) as a biomarker for hepatocellular carcinoma (HCC). PATIENTS AND METHODS: Ninety patients in four groups were enrolled in this prospective cross-sectional study: 30 with HCC (group I), 30 with liver cirrhosis (group II), 15 with hepatitis C virus infection (group III), and 15 healthy blood donors as controls. Alpha fetoprotein (AFP), CCL20 and vascular endothelial growth factor (VEGF) were measured in all groups. RESULTS: Serum levels of CCL20 were significantly different among the study groups (F=230.979, p<0.001). The highest level was found in HCC patients (57.305 ± 6.386 pg/mL) followed by patients with cirrhosis (45.999 ± 5.165 pg/mL) compared with 22.781 ± 5.986 pg/mL and 18.585 ± 3.554 pg/mL in asymptomatic patients with HCV infection and controls, respectively. In HCC patients, CCL20 significantly correlated with VEGF (r=0.559, p=0.001), AFP (r=0.814, p<0.001), Child score (r=0.748, p<0.001), and tumor size (r=0.825, p<0.001). The cutoff value of CCL20 for the detection of HCC in HCV-infected patients was 54 pg/mL with 93.1% accuracy, 89.6% negative predictive value, 92.6% positive predictive value, 83.3% sensitivity, and 93.3% specificity. In patients with cirrhosis, CCL20 significantly correlated with VEGF (r=0.455, p=0.011), AFP (r=0.975, p<0.001), and Child score (r=0.977, p<0.001). CONCLUSION: CCL20 may be used for the detection of HCC in HCV-infected patients with comparable specificity and higher sensitivity than AFP.

International field testing of the reliability and validity of the EORTC QLQ-BM22 module to assess health-related quality of life in patients with bone metastases.

BACKGROUND: The objective of this international field study was to test the reliability, validity, and responsiveness of the European Organization for Research and Treatment of Cancer (EORTC) QLQ-BM22 module to assess health-related quality of life (HRQOL) in patients with bone metastases. METHODS: Patients undergoing a variety of bone metastases-specific treatments were accrued. The QLQ-BM22 was administered with the QLQ-C30 at baseline and at 1 follow-up time point internationally. A debriefing questionnaire was administered to determine patient acceptability and understanding. RESULTS: Large-scale field testing of the QLQ-BM22 in addition to the QLQ-C30 took place in 7 countries: Brazil, Canada, Cyprus, Egypt, France, India, and Taiwan. A total of 400 patients participated. Multitrait scaling analyses confirmed 4 scales in the 22-item module. The scales were able to discriminate between clinically distinct patient groups, such as between those with a poor and those with a better performance status. The QLQ-BM22 was well received in all 7 countries, and the majority of patients did not recommend any significant changes from the module in its current form. CONCLUSIONS: The final QLQ-BM22 module contains 22 items and 4 scales assessing Painful Sites, Painful Characteristics, Functional Interference, and Psychosocial Aspects. Results confirmed the validity, reliability, cross-cultural applicability, and sensitivity of the 22-item EORTC QLQ-BM22. It is therefore recommended that the QLQ-BM22 be used in addition to the QLQ-C30 in clinical trials to assess HRQOL in patients with bone metastases.

Accelerated partial breast irradiation with low-dose-rate interstitial implant brachytherapy after wide local excision: 12-year outcomes from a prospective trial.

PURPOSE: To evaluate the long-term toxicity, cosmesis, and local control of accelerated partial breast irradiation with implant brachytherapy after wide local excision for Stage T1N0 breast cancer (BCa). MATERIALS AND METHODS: Between 1997 and 2001, 50 patients with Stage T1N0M0 BCa were treated in a Phase I-II protocol using low-dose-rate accelerated partial breast irradiation with implant brachytherapy after wide local excision and lymph node surgery. The total dose was escalated in three groups: 50 Gy (n = 20), 55 Gy (n = 17), and 60 Gy (n = 13). Patient- and physician-assessed breast cosmesis, patient satisfaction, toxicity, mammographic abnormalities, repeat biopsies, and disease status were prospectively evaluated at each visit. Kendall's tau (τ(ß)) and logistic regression analyses were used to correlate outcomes with dose, implant volume, patient age, and systemic therapy. RESULTS: The median follow-up period was 11.2 years (range, 4-14). The patient satisfaction rate was 67%, 67% reported good-excellent cosmesis, and 54% had moderate-severe fibrosis. Higher dose was correlated with worse cosmetic outcome (τ(ß) 0.6, p < .0001), lower patient satisfaction (τ(ß) 0.5, p < .001), and worse fibrosis (τ(ß) 0.4, p = .0024). Of the 50 patients, 35% had fat necrosis and 34% developed telangiectasias ≥1 cm(2). Grade 3-4 late skin and subcutaneous toxicities were seen in 4 patients (9%) and 6 patients (13%), respectively, and both correlated with higher dose (τ(ß) 0.3-0.5, p ≤ .01). One patient had Grade 4 skin ulceration and fat necrosis requiring surgery. Mammographic abnormalities were seen in 32% of the patients, and 30% underwent repeat biopsy, of which 73% were benign. Six patients had ipsilateral breast recurrence: five elsewhere in the breast, and one at the implant site. One patient died of metastatic BCa after recurrence. The 12-year actuarial local control, recurrence-free survival, and overall survival rate was 85% (95% confidence interval, 70-97%), 72% (95% confidence interval, 54-86%), and 87% (95% confidence interval, 73-99%), respectively. CONCLUSION: Low-dose-rate accelerated partial breast irradiation with implant brachytherapy provides acceptable local control in select early-stage BCa patients. However, treatment-related toxicity and cosmetic complications were significant with longer follow-up and at higher doses.

Breast conservation therapy for patients with locally advanced breast cancer.

Neoadjuvant chemotherapy achieves high response rates in patients with breast cancer and has been used to reduce tumor size and allow for breast conservation in individuals who initially required mastectomy. The goals of this approach are to achieve optimal locoregional control together with acceptable cosmesis. In the setting of locally advanced disease, breast preservation appears to be feasible for appropriately selected patients whose tumors show adequate downstaging in response to induction chemotherapy. Nevertheless, further prospective randomized trials are warranted to better evaluate the results of this approach as compared with mastectomy.

Clinical outcome of breast cancer occurring after treatment for Hodgkin's lymphoma: case-control analysis.

BACKGROUND: To evaluate diagnosis, management and outcome of breast cancer (BC) occurring after irradiation for Hodgkin's lymphoma (HL). METHODS: 39 cases of BC in 28 HL survivors were retrospectively reviewed. 21 patients were included in a case-control analysis. RESULTS: The median age at diagnosis of HL and BC was 25.3 and 45.3 years, respectively. The median interval to develop BC was 16.1 years. Eleven women (39.2%) had bilateral disease. Mode of detection of the index breast cancers was by mammographic screening in 17 patients (60.7%), palpable lump in 8 patients (28.6%), clinical examination in two patients (7.1%), and unknown in one patient (3.6%). Case-control analysis showed that histological features and prognosis of BC after HL were similar to those of primary BC, however, for BC after HL, mastectomy was the predominant surgery (P = .001) and adjuvant radiotherapy and anthracycline-based chemotherapy were less frequently used as compared to primary BC (P < .001 and .003, respectively). CONCLUSION: The previous history of HL does not appear to be a poor prognostic factor for BC occurring thereafter.

Lung dose-volume parameters and the risk of pneumonitis for patients treated with accelerated partial-breast irradiation using three-dimensional conformal radiotherapy.

PURPOSE: There are no data on how complication rates after accelerated partial-breast irradiation delivered by three-dimensional conformal radiotherapy are affected by treatment technique. We therefore examined the risk of pneumonitis in relation to lung dose-volume parameters. PATIENTS AND METHODS: Our prospective dose-escalation trial enrolled 198 treated patients from 2003 to 2007. Patients received 32 or 36 Gy in 4-Gy fractions, given twice daily: 29 (14%) were treated with pure photons; 149 (77%) with mixed photons and electrons; and 20 (10%) with protons. RESULTS: There were four cases of pneumonitis at 4, 4, 7, and 9 months after treatment. All were in the 36-Gy cohort and were treated with pure photons. The risk of pneumonitis for the two cohorts combined was: 17% (four of 24) for an ipsilateral lung volume (ILV) receiving 20 Gy or higher (ILV, 20 Gy) of 3% or higher (P = .0002 for comparison to ILV 20 Gy < 3%, Fisher's exact test); 20% (four of 20) for an ILV 10 Gy of 10% or higher (P = .0001); and 15% (four of 26) for an ILV 5 Gy of 20% or higher (P = .0002). CONCLUSION: The risk of pneumonitis appeared related to the ILV treated. This volume can be reduced by using mixed photons and electron when possible. We recommend that the ILV 20 Gy should be lower than 3%, the ILV 10 Gy lower than 10%, and the ILV 5 Gy lower than 20% when purely coplanar techniques are used.

Chest wall radiotherapy: middle ground for treatment of patients with one to three positive lymph nodes after mastectomy.

PURPOSE: To evaluate the outcomes for patients with Stage II breast cancer and one to three positive lymph nodes after mastectomy who were treated with observation or adjuvant radiotherapy to the chest wall (CW) with or without the regional lymphatics. METHODS AND MATERIALS: We retrospectively analyzed 238 patients with Stage II breast cancer (one to three positive lymph nodes) treated with mastectomy at the Massachusetts General Hospital between 1990 and 2004. The estimates of locoregional recurrence (LRR), disease-free survival (DFS), and overall survival were analyzed according to the delivery of radiotherapy and multiple prognostic factors. RESULTS: LRR and DFS were significantly improved by postmastectomy radiotherapy (PMRT), with a 5- and 10-year LRR rate without PMRT of 6% and 11%, respectively and, with PMRT, of 0% at both 5 and 10 years (p = .02). The 5- and 10-year DFS rate without PMRT was 85% and 75%, respectively, and, with PMRT, was 93% at both 5 and 10 years (p = .03). A similar benefit was found for patients treated with RT to the CW alone. The LRR, DFS, and overall survival rate for patients treated to the CW only was 0%, 96%, and 95% at 10 years, respectively. CONCLUSION: Our data suggest that adjuvant PMRT to the CW alone provides excellent disease control for patients with breast cancer <5 cm with one to three positive lymph nodes.

Breast cancer after treatment of Hodgkin's lymphoma: risk factors that really matter.

PURPOSE: To evaluate the risk of breast cancer (BC) and the contributing risk factors in women after supradiaphragmatic irradiation (SDI) for Hodgkin's lymphoma (HL). SUBJECTS AND METHODS: Medical records of 248 women 60 years of age or less who received SDI for stage I/II HL between 1964 and 2001 at Massachusetts General Hospital were retrospectively reviewed. RESULTS: The median age at SDI was 26 years (range, 5.7-59.3). The median follow-up was 15.2 years (range, 0.1-41.3). In 36 patients, BC developed (bilaterally in 11 patients) at a median interval of 18.4 years (range, 4.3-33.8) after SDI. Based on data from the National Cancer Institute Surveillance, Epidemiology, and End Results program, the standardized morbidity ratio (SMR) for the first BC after SDI was 9.78 (95% confidence interval [CI], 4.64-18.11, p < 0.0001). The SMR of patients who received radiation before age of 30 years was 19.05 (95% CI, 12.33-28.13) compared with 4.64 (95% CI, 2.31-8.30) for patients aged 30 years or more at the time of treatment (p < 0.00003). Risk for BC was significantly higher 15 years or more after SDI compared with the risk during the first 15 years (p = 0.0026). None of HL characteristics or treatment details was associated with higher risk of BC after adjusting for age and calendar time. CONCLUSIONS: Age at irradiation and time since therapy appear to be the only significant risk factors for development of BC after treatment of HL. The risk is significantly higher 15 years or more after radiation and for women treated before age 30 years. Long-term surveillance strategies are indicated for women at risk.

Breast cancer after treatment of Hodgkin's lymphoma: general review.

The improved survival rates among patients with Hodgkin's lymphoma over the past few decades have come with increased incidence of second malignancies. One of the major concerns among female survivors is the significantly elevated risk of breast cancer that appears with extended follow-up. In this review, we include the published literature regarding the risk of breast cancer after irradiation for Hodgkin's lymphoma. We also present the possible long-term surveillance strategies and the optimal time to start screening these women. This could potentially help in early detection of secondary breast cancers and consequently improve outcomes. Furthermore, because of prior radiotherapy, the management of the breast cancer among this unique population has been controversial. We discuss the characteristics of breast cancer that occurs after Hodgkin's lymphoma and also treatment options that could be implemented.