Local-regional Recurrence In Patients Research Articles

American Radium Society Appropriate Use Criteria Postmastectomy Radiation Therapy: Executive Summary of Clinical Topics

To conduct an appropriate use criteria expert panel update on clinical topics relevant to current clinical practice regarding postmastectomy radiation therapy (PMRT). An analysis of the medical literature from peer-reviewed journals was conducted from May 4, 2010 to May 4, 2022 using the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines to search the PubMed database to retrieve a comprehensive set of relevant articles. A well-established methodology (modified Delphi) was used by the expert panel to rate the appropriate use of procedures. Evidence for key questions in PMRT regarding benefit in special populations and technical considerations for delivery was examined and described. Risk factors for local-regional recurrence in patients with intermediate-risk disease that indicate benefit of PMRT include molecular subtype, age, clinical stage, and pathologic response to neoadjuvant chemotherapy. Use of hypofractionated radiation in PMRT has been examined in several recent randomized trials and is under investigation for patients with breast reconstruction. The use of bolus varies significantly by practice region and has limited evidence for routine use. Adverse effects occurred with both PMRT preimplant and postimplant exchange in 2-staged breast reconstruction. Most patients with even limited nodal involvement will likely benefit from PMRT with significant reduction in local-regional recurrence and potential survival. Patients with initial clinical stage III disease and/or any residual disease after neoadjuvant chemotherapy should be strongly considered for PMRT. Growing evidence supports the use of hypofractionated radiation for PMRT with equivalent efficacy and decreased acute side effects, but additional evidence is needed for special populations. There is limited evidence to support routine use of bolus in all patients. Timing of PMRT regarding completion of 2-staged breast reconstruction requires a discussion of increased risks with radiation postimplant exchange compared with increased risk of failure of reconstruction or surgical complications with radiation preimplant exchange.

Pattern of Recurrence in 428 Patients With Thoracic Esophageal Squamous Cell Carcinoma After Radical Surgery and Its Implication in Postoperative Radiotherapeutic Clinical Target Volume.

PurposeThis study aimed to analyze the recurrence patterns of thoracic esophageal squamous cell carcinoma (ESCC) after radical surgery, and to understand its implication in the clinical target volume (CTV) design of postoperative radiotherapy (PORT) in patients with ESCC.Methods and materialsA total of 428 recurrent ESCC patients after radical surgery between 2014 and 2018 were included in this study. Recurrence patterns, especially anastomotic and regional lymph node recurrence (LNR), were analyzed. A T-shaped CTV were proposed for PORT and were evaluated whether it could cover most of regional LNR.ResultsThese patients all experienced anastomotic and/or regional LNR. Among the 428 patients, 27 cases (6.3%) had anastomotic recurrence only, and184 cases (43.0%) had LNR only. Those sites with an LNR rate higher than 15% in upper thoracic ESCC were as follows: No.101, No.104R, No.104L, No.106recR, No.106recL, No.106pre, No.106tb, No.107, and No. 109. Those with middle thoracic ESCC were as follows: No.104R, No.104L, 106recR, No.106recL, No.106pre, No.106tb, and No.107. Lastly, individuals with lower thoracic ESCC were as follows: No.104L, 106recR, No.106recL, No. 106pre, No. 106tb, No.107, and abdominal No. 3. The proportion of LNR not included in the proposed T-shaped CTV was 12.5% (1/8), 4.7% (6/128), and 10.4% (5/48) in the upper, middle, and lower thoracic segments, respectively.ConclusionsLNR was the most common type of local-regional recurrence in patients after radical surgery. Supraclavicular, superior and middle mediastinal lymph nodes had the highest recurrence rate, the rate of LNR which was outside T-shaped PORT CTV we proposed was less than 15%.

Extended Right Sided Colon Resection Increases the Risk of Post-Operative Complications and Does Not Reduce the Risk of Colon Cancer Local-Regional Recurrence: Nation-Wide Population-Based Study from Danish Colorectal Cancer Group Database

Background: It is controversial whether extensive resection of right-sided colon cancer (RSCC) confer oncological benefits. The aim of this study was to examine short-and long terms outcomes of extended (ERHC) surgical removal of mesocolon compared to conventional approach (CRHC). Method: This was a retrospective population-based study based on a prospectively maintained Danish Colorectal Cancer Group database. Primary outcome measure was local-regional recurrence in patients who underwent curative resection for RSCC and secondary outcome measures was 30-day post-operative complications. Distant metastasis, unplanned intraoperative adverse events (UIAEs), 30-and 90-day post-operative mortality were also investigated. Patients who had palliative or compromised resection, emergency surgery and neo-adjuvant chemo-therapy were excluded. Results: Of the 12,855 patients with RSCC retrieved, 1,151 underwent ERHC. Patients who had ERHC were younger males with a lower ASA scores, operated by colorectal surgeons, using laparoscopic approach and had a significant higher number of harvested lymph nodes.The rate of local-regional recurrence was 1.1% (136/12,855). 1.5% (249/17.174) with no difference between CRHC and ERHC (OR 1.7 CI 95% 0.63-2.18). Post-operative complications were significantly higher in ERHC even after adjusting for age, comorbidity, access to abdomen and other covariates (OR 1.26 CI 95% 1.01-1.58). No significant difference was noticed between CRHC and ERHC in the rates of distant metastasis, UIAEs and mortality. Conclusion: This large population-based registry study showed no difference in local-regional recurrence of RSCC between conventional and extended right hemicolectomy with mesenteric resection and ligation of the middle colic vessels. Extended resection was associated with higher rates of postoperative complications. Funding Statement: None. Declaration of Interests: None Ethics Approval Statement: The data retrieved from DCCG database were fully anonymized so that none of the patient in the dataset could be traced. Data management was conducted according to the national ethical guidelines. Danish Data Protection Agency (Datatilsynet) approval was obtained (RN-2018-94).

Local-regional recurrence risk after autologous fat grafting in breast cancer patients: A systematic review and meta-analysis.

This meta-analysis aims to determine whether autologous fat grafting (AFG) affects the risk of local-regional recurrence (LRR) in breast cancer patients. In pooled analyses of 11 eligible studies, AFG was not associated with increased LRR. Subgroup analyses showed that AFG did not increase the risk of LRR in patients undergoing breast-conserving surgery or mastectomy, in patients with in situ carcinomas or invasive carcinomas, or in patients undergoing postoperative radiotherapy.

Prognostic Factors of Local-Regional Recurrence in Patients with Operable Breast Cancer in Asia: A Meta-Analysis.

BACKGROUND:Cause of recurrence of breast cancer is multifactorial. Also, the occurrence of breast cancer in Asian patients has some different factors from the recurrence of breast cancer in western countries.AIM:This study aims to determine the prognostic factors of local-regional recurrence in patients with operable breast cancer in Asia.METHODS:The authors conducted a meta-analysis of published research articles published in an online database of PubMed, ProQuest and EBSCO between January 2000 and July 2018. Pooled risk ratios (RR) were calculated using fixed and random-effect models. Data were processed by using Review Manager 5.3 (RevMan 5.3).RESULTS:This study reviewed 879 articles. There were 11 studies conducted a systematic review then continued by meta-analysis of relevant data with total patients involved were 5,213 patients. The prognostic factors found of local-regional recurrence in patients with operable breast cancer were Nodal (N) stage with the highest risk ratio (RR = 6.35 [95% CI 3.78-10.67]) followed by HER2 positive (RR = 2.14 [95% CI 1.16-3.97]), stage of cancer (RR = 1.82 [95% CI 1.44-2.31]), tumor size (RR = 1.55 [95% CI 1.04-2.31]), tumor grade (RR = 1.43 [95% CI 1.23-1.65]), PR status (RR = 0.65 [95% CI 0.48-0.88]) and the least was ER status (RR = 0.60 [95% CI 0.39-0.91]). Homogeneity of variance was found in N stage, tumor size and tumor grade for recurrence of operable breast cancer.CONCLUSION:This meta-analysis confirmed the correlation of N stage, HER2, stage of cancer, tumour size, tumour grade, ER and PR status with recurrence in patients with operable breast cancer in Asia.

Benefits of postoperative radiotherapy in multimodality treatment of resected small-cell lung cancer with lymph node metastasis

AimThe purpose of this study is to evaluate the role of postoperative radiotherapy (PORT) in resected small-cell lung cancer (SCLC).Methods: This study retrospectively analyzed 143 patients with completely resected SCLC in our institution between 1996 and 2011. The primary endpoint was overall survival (OS). The log-rank test and Cox regression model were used to evaluate the factors influencing local-regional recurrence (LRR) and OS. ResultsThe median OS for the entire population was 34 months, and the 5-year OS rate was 34.6%. In multivariate analysis, age, surgical procedure, pathology stage, adjuvant chemotherapy and distant relapse were significant factors for survival. For the whole population, PORT had no effect on OS, with a median OS of 40 months in the PORT group versus 27 months in the non-PORT group (p = 0.260). However, in patients with N1 disease, the median OS were 40 months in the PORT group versus 14 months in the non-PORT group (p = 0.032). The corresponding OS in N2 patients were 35 months versus 17 months, respectively (p = 0.040). Similarly, PORT significantly reduced the LRR in patients with positive lymph node. For patients with N1 disease, the 3-year LRR rate was 0.0% in the PORT group versus 14.3% in the non-PORT group (p = 0.037). The corresponding LLR rate in N2 patients was 4.2% versus 56.6% (p < 0.001). ConclusionPORT significantly reduced LRR and improved OS in patients with regional metastasis SCLC. We suggest supplementing PORT in the multimodality treatment of resected SCLC with lymph node metastasis.

Abstract P3-14-12: Risk factors for local regional recurrence in patients undergoing breast conserving surgery following neoadjuvant chemotherapy and validation of the MD Anderson prognostic index

Abstract Background: Breast conserving surgery (BCS) is a primary goal of neoadjuvant chemotherapy (NAC) in patients with locally advanced breast cancer, especially with recent improvements in tumor response. Patient selection for BCS following NAC may be different than classic local regional recurrence (LRR) risk factors. Here we investigate risk factors for LRR and attempt to validate the MD Anderson Prognostic Index (MDAPI) for LRR in a single institution series. Methods: Data were analyzed for 178 consecutive patients treated at one institution who underwent NAC followed by BCS and whole breast radiotherapy between the years 1999 and 2011. Using univariate and multivariate analysis, multiple clinicopathologic factors were investigated, as well as the subgroups of the MDAPI. Chi-square tests were used to compare the LRR-free survival rates between subgroups. Results: The median follow-up was 70.33 months and the 5-year LRR-free survival was 93.18%. Multivariate analysis demonstrated that clinical stage and pathologic stage were both statistically significant for LRR-free survival, while pattern of residual disease was of borderline statistical significance. The MDAPI was not significantly associated with LRR-free survival (MDAPI low 93.80%, Intermediate 88.23%, High 88.89%). Five-Year Local Regional Recurrence -Free Survival According to Clinicopathologic Factors # Patients5yr LRR-Free SurvivalPathologic Stage p = 0.03301580.0%14292.5%27692.5%3994.6%pCR38100%Clinical Stage p = 0.0291580.0%213796.3%33883.8%MDAPI Score P = 0.506Low (0 or 1)12993.80%Int (2)3488.23%High (3)988.89%*MDAPI Score Factors cN Stage P = 0.305cN0-N116593.3%cN2-N31070%LVI P = 0.453No-LVI15793.5%Yes-LVI2390.9%pT&amp;gt;2cm P = 0.158Residual Tumor Morphology P = 0.055Multifocal Resid Tumor5996.5%Solitary Mass6690.6%No Resid Tumor5394.3%*These factors make up the MDA Prognostic Index Conclusion: Overall the 5-year LRR-free survival was high at 93.18%, which compares favorably to similar neoadjuvant patient cohorts who receive mastectomy instead of BCS. Our analysis indicates clinical stage and pathologic stage are significant in predicting LRR. Of the four predictive factors utilized by the MDAPI, only multifocal residual disease showed weak predictive power (p = 0.055) in our population; however, it correlated with higher LRR-free survival, the opposite of its indication in the MDAPI. The MDAPI was not useful in our patient population; the risk groups did not significantly correlate with LRR-free survival. This may be secondary to low total number of recurrence events and also the small number of patients in the MDAPI-high group (9 patients had an MDAPI score of 3, and none had a score of 4). As further data emerge regarding biology of tumors and recurrence, it may be a combination of molecular profiling and residual cancer burden that is a better predictor for LRR. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-14-12.

Total Skin-Sparing Mastectomy in BRCA Mutation Carriers

Total skin-sparing mastectomy (TSSM) with preservation of the nipple-areolar complex skin has become increasingly accepted as an oncologically safe procedure. Oncologic outcomes after TSSM in BRCA mutation carriers have not been well-studied. We identified 53 BRCA-positive patients who underwent bilateral TSSM for prophylactic (26 patients) or therapeutic indications (27 patients) from 2001 to 2011. Cases were age-matched (for prophylactic cases) or age- and stage-matched (for therapeutic cases) with non-BRCA-positive patients. Outcomes included tumor involvement of resected nipple tissue, the development of new breast cancers in patients who underwent risk-reducing TSSM, and local-regional recurrence in patients who underwent therapeutic TSSM. Outcomes from 212 TSSM procedures in 53 cases and 53 controls were analyzed. In patients undergoing TSSM for prophylactic indications, in situ cancer was found in one (1.9 %) nipple specimen in BRCA-positive patients versus two specimens (3.8 %) in the non-BRCA-positive cohort (p = 1). At a mean follow-up of 51 months, no new cancers developed in either cohort. In patients undergoing TSSM for therapeutic indications, in situ or invasive cancer was found in zero of the nipple specimens in BRCA-positive patients versus two specimens (3.7 %) in the non-BRCA-positive cohort (p = 0.49). At a mean follow-up of 37 months, there were no local-regional recurrences in the BRCA-positive cohort and 1 (3.7 %) in the non-BRCA-positive cohort. TSSM is an oncologically safe procedure in BRCA-positive patients. In patients undergoing TSSM as a risk-reducing strategy, 4-year follow-up demonstrates no increased risk of developing new breast cancers; longer-term follow-up is ongoing.

Abstract P4-14-04: Total skin-sparing mastectomy in BRCA mutation carriers

Abstract BACKGROUND: Total skin-sparing mastectomy (TSSM) with preservation of the nipple-areolar complex skin has become increasingly accepted as an oncologically safe procedure for both prophylactic and therapeutic indications. The goal of this study was to evaluate the oncologic outcomes after TSSM in BRCA mutation carriers. METHODS: We identified 53 BRCA-positive patients who underwent bilateral TSSM for prophylactic (27 patients) or therapeutic (26 patients) indications from 2001 to 2011. Cases were age-matched (for prophylactic cases) or age- and stage-matched (for therapeutic cases) with non-BRCA-positive patients who underwent bilateral TSSM during this time period. Outcomes included tumor involvement of the resected nipple tissue, the development of new breast cancers in patients who underwent bilateral risk-reducing TSSM, and the development of any local-regional recurrence in patients who underwent therapeutic TSSM. RESULTS: Outcomes from 212 TSSM procedures in 53 cases and 53 controls were analyzed. In patients undergoing TSSM for prophylactic indications, in situ cancer was found in 1 (1.9%) of the nipple specimens in the BRCA-positive patients vs. 2 specimens (3.7%) in the non-BRCA-positive cohort (p = 1). At a mean follow-up of 56 months, no new cancers developed in the BRCA-positive or the non-BRCA-positive cohorts. In patients undergoing TSSM for therapeutic indications, in situ or invasive cancer was found in 0 of the nipple specimens in the BRCA-positive patients vs. 2 specimens (3.9%) in the non-BRCA-positive cohort (p = 0.49). At a mean follow-up of 33 months, there were no local-regional recurrences in the BRCA-positive cohort. CONCLUSIONS: TSSM is an oncologically safe procedure in BRCA-positive patients, as is evidenced by the low rates of tumor involvement of the nipple tissue and local-regional recurrence after therapeutic mastectomy. In BRCA-positive patients undergoing TSSM as a risk-reducing strategy, five-year follow-up demonstrates no increased risk for the development of new breast cancers; longer-term follow-up is anticipated to further confirm its safety. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-14-04.

Surgical Margins and the Risk of Local-Regional Recurrence After Mastectomy Without Radiation Therapy

Although positive surgical margins are generally associated with a higher risk of local-regional recurrence (LRR) for most solid tumors, their significance after mastectomy remains unclear. We sought to clarify the influence of the mastectomy margin on the risk of LRR. The retrospective cohort consisted of 397 women who underwent mastectomy and no radiation for newly diagnosed invasive breast cancer from 1998-2005. Time to isolated LRR and time to distant metastasis (DM) were evaluated by use of cumulative-incidence analysis and competing-risks regression analysis. DM was considered a competing event for analysis of isolated LRR. The median follow-up was 6.7 years (range, 0.5-12.8 years). The superficial margin was positive in 41 patients (10%) and close (≤2 mm) in 56 (14%). The deep margin was positive in 23 patients (6%) and close in 34 (9%). The 5-year LRR and DM rates for all patients were 2.4% (95% confidence interval, 0.9-4.0) and 3.5% (95% confidence interval, 1.6-5.3) respectively. Fourteen patients had an LRR. Margin status was significantly associated with time to isolated LRR (P=.04); patients with positive margins had a 5-year LRR of 6.2%, whereas patients with close margins and negative margins had 5-year LRRs of 1.5% and 1.9%, respectively. On univariate analysis, positive margins, positive nodes, lymphovascular invasion, grade 3 histology, and triple-negative subtype were associated with significantly higher rates of LRR. When these factors were included in a multivariate analysis, only positive margins and triple-negative subtype were associated with the risk of LRR. Patients with positive mastectomy margins had a significantly higher rate of LRR than those with a close or negative margin. However, the absolute risk of LRR in patients with a positive surgical margin in this series was low, and therefore the benefit of postmastectomy radiation in this population with otherwise favorable features is likely to be small.

Impact of Partially Untreated Breast Target Volume on the Local Regional Recurrence in Patients with Early-stage Left Breast Cancer

Impact of Partially Untreated Breast Target Volume on the Local Regional Recurrence in Patients with Early-stage Left Breast Cancer

Surgical margins and the risk of local-regional recurrence (LRR) following mastectomy for early-stage breast cancer.

95 Background: We sought to clarify the influence of a positive or close superficial or deep mastectomy margin on the risk of LRR. Methods: We reviewed the charts of 561 consecutive women who underwent mastectomy without radiation for newly diagnosed in situ or invasive breast cancer between 1998 and 2005. The study cohort consists of 167 of these women who had a positive or close (≤2 mm) superficial or deep surgical margin. LRR as the site of first recurrence (+/− simultaneous distant disease) and distant metastasis (DM) rates were calculated using the Kaplan-Meier method. The median age was 50 years. Forty-five (27%) had ductal carcinoma in situ (DCIS) only. Of the 122 women with invasive disease, 79% had T1, 18% T2, and 3% T3 tumors, and 25% had positive axillary nodes (range, 1-4; 68% 1 positive node). Twenty-nine (24%) of those with invasive disease had lymphovascular invasion. The superficial margin was positive in 61 (37%) and close in 69 (41%). The deep margin was positive in 28 (17%) and close in 51 (31%). Results: The median follow-up was 6.3 years (range, 1-12.4). The 5-year LRR rate was 5% (95% CI 2-10%) and the DM rate was 3% (95% CI 1-8%). Twelve patients had a LRR; this included the chest wall in 9 and the axilla in 4. Five of the 12 had positive nodes. Four of 92 (4%) with close margins had a LRR vs. 8/75 (11%) with positive margins (log-rank p=0.15). Of the 45 with pure DCIS, 1 (2%) had a LRR. Of those with invasive disease, LRR occurred in 1/28 (4%) who had invasive disease at (positive) or near (close) the superficial margin, 3/38 (8%) with DCIS at or near the superficial margin, 0/12 with invasive disease at or near the deep margin, and 1/12 (8%) with DCIS at or near the deep margin. Both margins were positive or close in 32/122 patients with invasive disease; 6 of these (19%) had a LRR. Conclusions: The risk of LRR in patients with a positive or close surgical margin after mastectomy is generally low. The benefit of post-mastectomy radiation in this population with otherwise favorable features is likely to be small. While there may be a higher risk of LRR in patients with disease at or close to both margins (likely representing extent of disease), numbers in these categories are small and these results should be interpreted with caution.

Does the revised TNM staging system for lung cancer better estimate actuarial rates of local/regional recurrence after surgery?

7072 Background: The International Association for the Study of Lung Cancer (IASLC) recently recommended changes to the TNM classification of lung cancers. For early-stage disease, increasing tumor size and nodal status are of primary prognostic relevance for overall survival. However, the ability of the old and the new staging system to predict the risk of local/regional recurrence (LRR) has not been evaluated. Therefore, we examined whether the proposed changes in AJCC 7 would refine the risk of LRR in patients who undergo surgery for early-stage NSCLC. Methods: The medical records and pertinent radiographs for all patients who underwent surgery for early-stage (N0-N1) NSCLC at Duke between 1995 and 2005 were reviewed. Patients undergoing suboptimal surgery (sublobar resections, positive margins), or those who received any preoperative therapy or postoperative radiation therapy were excluded. Disease recurrence at the surgical margin, ipsilateral hilum, and/or mediastinum was considered a LRR. Stage was assigned based on both AJCC 6 and AJCC 7. Actuarial rates of LRR were estimated using the Kaplan-Meier method. Results: Of 975 patients who underwent surgery during the time interval, 741 were eligible for this analysis. Surgery consisted of lobectomy in 91% (n=672) and pneumonectomy in 9% (n=69) of patients. 82% (n=605) of patients were pathologic N0 (pN0) and 18% (n=136) were pN1. Adjuvant chemotherapy was administered to 7% (n=52). Median follow-up was 35 months. Conversion from AJCC 6 to AJCC 7 resulted in 25% stage migration (upstaging in 15%; downstaging in 10%). For all patients, the 5-year actuarial risk of LRR was 20% (95% CI 17%-24%). 5-year rates of LRR for stage IA, IB, IIA, and IIB disease using AJCC 6 were 12%, 26%, 40%, and 27%, respectively. Using AJCC 7, corresponding rates were 12%, 21%, 34%, and 38%, respectively. Conclusions: The risk of LRR increases monotonically with stage in the new AJCC 7 system, but not for the older AJCC 6 system. Thus, the newer staging system is better in predicting the risk of LRR. This information will be valuable when designing future studies of postoperative RT. No significant financial relationships to disclose.

1022 POSTER Patterns of local-regional recurrence in patients with head and neck cancer treated by parotid-sparing IMRT

1022 POSTER Patterns of local-regional recurrence in patients with head and neck cancer treated by parotid-sparing IMRT

In reply to Dr. Monsour

In reply to Dr. Monsour

Risk factors for local-regional recurrence following preoperative radiation therapy and surgery for head and neck cancer (stage II-IVB).

To discover possible risk factors for local-regional recurrence (LRR) following preoperative radiation therapy and curative surgery for head and neck squamous cell carcinoma (SCC) (stage II-IVB). Clinical records from 1987 to 1999 of 161 patients with head and neck SCC (oral cavity, 80 patients; larynx, 50; hypopharynx, 19; oropharynx, 12) who underwent preoperative radiation therapy and surgery were retrospectively reviewed. One hundred thirty-two (82%) of the patients had stage III or IV cancer. The median radiation dose was 38 Gy. The 5-year overall survival rate and LRR rate were 58% and 35%, respectively. At multivariate analysis, oral cavity cancer (P =.020), clinical T stage (P =.016), clinical N stage (P =.017), and status of surgical margins (P =.008) emerged as variables that were significantly associated with LRR. The analysis of only those patients with lymph node involvement showed that oral cavity cancer (P =.008), advanced N-stage cancer (P =.045), and long interval between the start of preoperative radiation therapy and surgery (> or =7 weeks) (P =.019) emerged as variables that were significantly associated with LRR. Oral cavity cancer, advanced T or N stage of disease, and unsatisfactory margins were risk factors for LRR. A long interval (> or =7 weeks) was a risk factor for LRR in patients with lymph node involvement.

Patterns of local-regional recurrence following parotid-sparing conformal and segmental intensity-modulated radiotherapy for head and neck cancer

Purpose: To analyze the patterns of local-regional recurrence in patients with head and neck cancer treated with parotid-sparing conformal and segmental intensity-modulated radiotherapy (IMRT). Methods and Materials: Fifty-eight patients with head and neck cancer were treated with bilateral neck radiation (RT) using conformal or segmental IMRT techniques, while sparing a substantial portion of one parotid gland. The targets for CT-based RT planning included the gross tumor volume (GTV) (primary tumor and lymph node metastases) and the clinical target volume (CTV) (postoperative tumor bed, expansions of the GTVs and lymph node groups at risk of subclinical disease). Lymph node targets at risk of subclinical disease included the bilateral jugulodigastric and lower jugular lymph nodes, bilateral retropharyngeal lymph nodes at risk, and high jugular nodes at the base of skull in the side of the neck at highest risk (containing clinical neck metastases and/or ipsilateral to the primary tumor). The CTVs were expanded by 5 mm to yield planning target volumes (PTVs). Planning goals included coverage of all PTVs (with a minimum of 95% of the prescribed dose) and sparing of a substantial portion of the parotid gland in the side of the neck at less risk. The median RT doses to the gross tumor, the operative bed, and the subclinical disease PTVs were 70.4 Gy, 61.2 Gy, and 50.4 Gy respectively. All recurrences were defined on CT scans obtained at the time of recurrence, transferred to the pretreatment CT dataset used for RT planning, and analyzed using dose–volume histograms. The recurrences were classified as 1) “in-field,” in which 95% or more of the recurrence volume (V recur) was within the 95% isodose; 2) “marginal,” in which 20% to 95% of V recur was within the 95% isodose; or 3) “outside,” in which less than 20% of V recur was within the 95% isodose. Results: With a median follow-up of 27 months (range 6 to 60 months), 10 regional recurrences, 5 local recurrences (including one noninvasive recurrence) and 1 stomal recurrence were seen in 12 patients, for a 2-year actuarial local-regional control rate of 79% (95% confidence interval 68–90%). Ten patients (80%) relapsed in-field (in areas of previous gross tumor in nine patients), and two patients developed marginal recurrences in the side of the neck at highest risk (one in the high retropharyngeal nodes/base of skull and one in the submandibular nodes). Four regional recurrences extended superior to the jugulodigastric node, in the high jugular and retropharyngeal nodes near the base of skull of the side of the neck at highest risk. Three of these were in-field, in areas that had received the dose intended for subclinical disease. No recurrences were seen in the nodes superior to the jugulodigastric nodes in the side of the neck at less risk, where RT was partially spared. Conclusions: The majority of local-regional recurrences after conformal and segmental IMRT were “in-field,” in areas judged to be at high risk at the time of RT planning, including the GTV, the operative bed, and the first echelon nodes. These findings motivate studies of dose escalation to the highest risk regions.

Long-term follow-up of axillary node-positive breast cancer patients receiving adjuvant tamoxifen alone: patterns of recurrence

Purpose: To determine the patterns, incidence and risk factors for local-regional recurrence in patients with Stage II and III breast cancer treated with adjuvant tamoxifen alone, without adjuvant radiation. Material and Methods: The records of patients referred to the London Regional Cancer Centre with a diagnosis of breast cancer between 1980–1989 were reviewed. During this time period, it was the policy of the institution to omit local-regional radiation to patients receiving adjuvant systemic therapy. One hundred and fifty axillary node-positive Stage II and III breast cancer patients received adjuvant tamoxifen alone without postoperative local-regional radiation; these patients form the basis of this report. Results: Median follow-up was 67 months for the entire patient group and 85 months for the living patients. During this time, 42% of patients developed a recurrence, 22% first recurred in local-regional sites. The total incidence of local-regional recurrence (including those patients who first relapsed with systemic metastases) was 30%. Of the segmental mastectomy patients, 13% had recurrences in the intact breast. Of the modified radical mastectomy patients, 10% developed chest wall recurrences. Five percent of recurrences were first in the axilla and 6% in the supraclavicular nodes. Five-year actuarial survival for the entire patient group was 79% and disease-free survival was 60%, with a median disease-free survival time of 87 months. Five-year local-regional relapse-free survival was 76%. Five-year local-regional relapse-free survival was < 76% for those patients with 4 or more positive axillary nodes, regardless of tumor size. On univariable analysis, positive resection margins, number of positive axillary nodes, menopausal status, and negative estrogen and progesterone receptors were significant for isolated local-regional recurrence. On multivariable analysis, only positive resection margins and negative receptors remained significant. In terms of regional recurrence specifically, negative estrogen and progesterone-receptor status and positive resection margins were, again, prognostically significant. Conclusions: Postmenopausal women receiving adjuvant tamoxifen who have positive resection margins, ≥ 4 positive axillary nodes and/or negative estrogen and progesterone receptors, are at higher risk of local and regional recurrence and should, therefore, receive local-regional radiation.

The role of mastectomy in patients with stage I-II breast cancer presenting with gross multifocal or multicentric disease or diffuse microcalcifications

Purpose: Women with Stage I–II invasive breast cancer who present with gross multicentric disease or diffuse microcalcifications have a significant risk of breast recurrence when treated with conservative surgery and radiation. The purpose of this report is to present the results of mastectomy in this group of patients. Methods and Materials: Between 1982 and 1989, 88 patients with clinical Stage I–II breast cancer who presented with clinical and mammographic evidence of gross multicentric disease or diffuse microcalcifications underwent modified radical mastectomy. Median followup was 4 years for the 57 patients with gross multicentric disease and 5.6 years for 31 patients with diffuse microcalcifications. At the time of mastectomy, 42% of patients were found to have positive axillary nodes. Following mastectomy, 15 patients received post mastectomy radiation and 35 patients received adjuvant systemic chemotherapy. Results: When compared to a group of 1295 patients with unifocal, Stage I–II breast cancer, treated with conservative surgery and radiation during the same time period, patients with gross multicentric disease and diffuse microcalcifications had a significantly higher incidence of ≥ 4 positive nodes, patients with gross multicentric disease had a lower incidence of positive resection margins following mastectomy and patients with diffuse microcalcifications were younger. The 5-year actuarial risk of an isolated local-regional recurrence was 8% for patients with gross multicentric disease or diffuse microcalcifications and 7% for patients with unifocial disease. Patients with gross multicentric disease or diffuse microcalcifications and ≥ 4 positive axillary nodes who did not receive post mastectomy radiation had an increased risk for local regional recurrence. There were no significant differences in the 5-year actuarial overall or relapse-free survival (88% and 73% gross multicentric disease, 97% and 86% diffuse microcalcifications and 90% and 79% unifocal disease), freedom from distant metastasis (76% gross multicentric disease, 90% diffuse microcalcifications, 86% unifocal disease) or incidence of contralateral breast cancer (10% gross multicentric disease, 13% diffuse microcalcifications, 8% unifocal disease) among the three groups. Conclusion: The present study demonstrates no increased risk of local-regional recurrence in patients with gross multicentric disease or diffuse microcalcifications undergoing mastectomy in contrast to the increased risk of breast recurrence in patients with gross multicentric disease undergoing conservative surgery and radiation. Indications for post mastectomy radiation include ? 4 positive nodes or close or positive surgical margins. Despite a significantly higher incidence of ≥ 4 positive nodes, patients with gross multicentric disease and diffuse microcalcifications have a 5-year actuarial overall and relapse-free survival comparable to a group of patients with unifocal disease treated with conservative surgery and radiation.