Incidence Of Regional Recurrence Research Articles

Breast-Conserving Surgery with or without Irradiation in Early Breast Cancer

BackgroundLimited level 1 evidence is available on the omission of radiotherapy after breast-conserving surgery in older women with hormone receptor–positive early breast cancer receiving adjuvant endocrine therapy.MethodsWe performed a phase 3 randomized trial of the omission of irradiation; the trial population included women 65 years of age or older who had hormone receptor–positive, node-negative, T1 or T2 primary breast cancer (with tumors ≤3 cm in the largest dimension) treated with breast-conserving surgery with clear excision margins and adjuvant endocrine therapy. Patients were randomly assigned to receive whole-breast irradiation (40 to 50 Gy) or no irradiation. The primary end point was local breast cancer recurrence. Regional recurrence, breast cancer–specific survival, distant recurrence as the first event, and overall survival were also assessed.ResultsA total of 1326 women were enrolled; 658 were randomly assigned to receive whole-breast irradiation and 668 to receive no irradiation. The median follow-up was 9.1 years. The cumulative incidence of local breast cancer recurrence within 10 years was 9.5% (95% confidence interval [CI], 6.8 to 12.3) in the no-radiotherapy group and 0.9% (95% CI, 0.1 to 1.7) in the radiotherapy group (hazard ratio, 10.4; 95% CI, 4.1 to 26.1; P<0.001). Although local recurrence was more common in the group that did not receive radiotherapy, the 10-year incidence of distant recurrence as the first event was not higher in the no-radiotherapy group than in the radiotherapy group, at 1.6% (95% CI, 0.4 to 2.8) and 3.0% (95% CI, 1.4 to 4.5), respectively. Overall survival at 10 years was almost identical in the two groups, at 80.8% (95% CI, 77.2 to 84.3) with no radiotherapy and 80.7% (95% CI, 76.9 to 84.3) with radiotherapy. The incidence of regional recurrence and breast cancer–specific survival also did not differ substantially between the two groups.ConclusionsOmission of radiotherapy was associated with an increased incidence of local recurrence but had no detrimental effect on distant recurrence as the first event or overall survival among women 65 years of age or older with low-risk, hormone receptor–positive early breast cancer. (Funded by the Chief Scientist Office of the Scottish Government and the Breast Cancer Institute, Western General Hospital, Edinburgh; ISRCTN number, ISRCTN95889329.)

Stereotactic ablative radiotherapy versus surgery in older patients with stage I lung cancer.

Surgical resection is the best option for the treatment of early-stage lung cancer. However, older patients are less likely to receive curative treatment. Therefore, we compared long-term survival rates between surgical resection and stereotactic ablative radiotherapy (SABR) for the treatment of early-stage lung cancer in older patients. From 2013 to 2016, 272 patients aged ≥75 years with clinical stage I lung cancer underwent surgical resection (n = 191) or SABR (n = 81). A propensity score-matched analysis was performed. Overall survival, cumulative incidence of cancer-related death and recurrence were compared between the 2 groups. In the matched cohort, 48 well-balanced pairs were extracted. An overall survival benefit was associated with surgery (surgery vs SABR = 65.9% vs 40.3%; P = 0.034); however, there was no significant difference in the cumulative incidence of cancer-related death (P = 0.089) or recurrence (P = 0.111) between the 2 groups. Systemic dissemination was the dominant pattern of progression in both groups. The 3-year cumulative incidence of regional recurrence was significantly higher in the SABR group compared to the surgery group (surgery vs SABR = 0% vs 11.4%, P = 0.046). Surgical resection with mediastinal lymph node dissection provides better long-term survival compared to SABR in older patients with stage I lung cancer. Surgery should be considered for older patients aged ≥75 years who are appropriate candidates for surgery. SABR remains an alternative treatment with comparable cancer-related death and recurrence for patients unsuitable for surgery.

Incidence of Regional Recurrence Outside of Radiation Fields in Patients with or without Elective Nodal Irradiation for Stage I Middle Thoracic Esophageal Cancer

The appropriate field of elective nodal irradiation (ENI) for middle thoracic (Mt) esophageal cancer is still unclear. To evaluate the efficacy of ENI for stage I Mt esophageal cancer treated with radiotherapy (RT), we researched the incidence of recurrence outside of radiation fields in patients with and without ENI. From April 2006 to December 2014, 55 patients with stage I esophageal cancer mainly located at Mt received definitive RT with or without concurrent chemotherapy in our institution. Of these, 52 patients followed up for more than six months were examined in this study (age, 51-89, median 70; male/female = 46/6; chemoradiotherapy/RT alone = 43/9). Because of the change of institutional policy, ENI became to be performed in principle from 2013. Seventeen patients (33%) received ENI to the mediastinum with or without the supraclavicular region and the upper abdomen. Remaining 35 patients received irradiation only to the range where the margin of 3-4 cm was added above and below the gross tumor volumes. The median follow-up time was 51.8 months (2.5 to 126.5 months). A total of 11 patients (21%) relapsed: 4 (8.0%) developed local, 6 (12%) developed regional and 1 (2.0%) developed loco-regional. The regional recurrence outside of radiation fields occurred in two patients with ENI (12%) and in three patients without ENI (9%) (p=0.71). For patients with ENI, sites of regional recurrences were recurrent nerve lymph nodes (#106rec) in one case and lymph nodes along the lesser curvatures (#3) in one. For patients without ENI, sites of regional recurrences were #106rec in two cases, right cardiac lymph nodes (#2) in one, lymph nodes along the celiac artery in one and left cervical lymph nodes in one. Three-year overall survival rates (OS) and progression free survival rates (PFS) for all patients were 83% and 73%, respectively. Three-year OS for patients with and without ENI were 88% and 80%, respectively (p=0.52). Three-year PFS for patients with and without ENI were 77% and 71%, respectively (p=0.32). Incidence of lymph node recurrence outside of radiation fields did not differ significantly between patient with and without ENI for stage I Mt esophageal cancer. In addition, ENI did not improve OS and PFS significantly.

Early-Stage Lung Adenocarcinoma Treated With Stereotactic Body Radiation Therapy: Prognostic Factors for Treatment Outcomes

While stereotactic body radiotherapy (SBRT) has been well-established as an effective treatment for early-stage lung cancer, follow-up studies have suggested that the incidence of regional recurrence and distant metastasis can be significant. Given that the histologic subtype of lung adenocarcinoma on either surgical or core biopsy specimens has been recognized as a prognostic factor, we sought to evaluate outcomes after SBRT for early-stage lung adenocarcinoma based on this variable. A review of institutional registries identified 51 consecutive patients (55 lesions) with stage I to IIA lung adenocarcinoma who had undergone definitive SBRT at our institution from August 2009 to August 2016. Potentially prognostic indicators including International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society (IASLC/ATS/ERS) histologic subtypes of lung adenocarcinoma, positron emission tomography (PET) parameters of maximal standardized uptake value (SUVmax), PET volume (volume at 40% of SUVmax), PET volume multiply SUVmax and TLG (total lesion glycolysis), T stage and the pattern of initial presentation (uni- versus multi-focal) as well as pre-SBRT history of malignancy were analyzed to determine if there was an association with local, nodal, regional, distant failure and overall survival rates using logistic regression models. The median follow-up for the entire cohort was 2.17 years. The failure rates of local, nodal, regional, and distant were 5.6%, 19.2%, 25.9% and 24.5%, respectively. The overall survival rate was 71.2%. The PET parameters volume, volume times maximal SUV and TLG as well as T stage (T3 above) were identified as significant predictors (p<0.05) for local control. Any pre-SBRT history of malignancy was significantly associated with higher incidence of distant metastasis. The histologic subtype of adenocarcinoma and presentation of multi-focal lesions were not associated with treatment outcomes (p>0.05, for all). We demonstrated that volume of PET and T stage were significant predictors of local control after SBRT for early-stage adenocarcinoma of the lung. A history of prior malignancy was associated with a high incidence of distant metastasis. We are unable to identify histologic subtype of adenocarcinoma and multi-focal lesions at presentation as prognostic factors.

Ultrasound Dye-Assisted Surgery (USDAS) for Regional Recurrence in Head and Neck Cancer: A Case Report

The incidence of regional recurrence in oral squamous cell carcinoma(SCC) after the neck dissection is 32.7%. Regional failure after definite neck treatment not only relates to poor prognosis but also leads to higher complication rate in the salvage neck dissection since the diseased structure is often surrounded by scar tissue and hard to be identified. The adequate and safe neck surgery is crucial for head and neck surgeons. Ultrasound dye-assisted surgery(USDAS) offers a simplified way to localize lesions clearly during the operation. Case report and literature review. We report a 53-year-old male who suffered from the left tongue border ulcer for 2 months. Transoral wide excision was performed for pT1, moderately differentiated SCC with negative p16 staining. 3 months later, the left level I neck mass was palpated. Sono-guided fine needle aspiration was done, and cytology revealed SCC. Bilateral neck dissection of the left level I-IV and the right level I-II was accomplished. Pathology reported ypN2b disease over the left level I and III with remarkable extracapsular spread(ECS) of the former one. However, the adjuvant concurrent chemoradiotherapy(CCRT) was incompletely conducted due to the progressive submental mass 5 weeks later. The sonography delineated one 1.33cm hypoechoic lesion with irregular boundary, incomplete halo and central necrosis over the midline of level IA. Fine needle aspiration was done, and cytology report confirmed SCC. For the adequately and completely wide excision of the malignancy, USDAS was done. Methyl blue in 1ml syringe was injected in the assistance with ultrasound-guided technique into the left periphery, right periphery, upper margin, lower margin and most importantly, the base of the tumor. Wide excision of the submental tumor was consequently executed. Final pathology indicated metastastic squamous cell carcinoma of dermis and subcutis sized 1.2cm. The closest surgical margin was 0.5cm from the peripheral margin. In our case, considering the infiltrative character of dermal pathology ensnared by postoperative fibrosis, USDAS was utilized to mark the surgical boundaries. Final pathology proved adequate margins, and there was no complication. This procedure offers precise localization with avoidance in unnecessary destruction and reduces operative time significantly. Based on the anatomic complexity in head and neck region, the USDAS can be extendedly used in the future. More studies investigating exact decreasing rate of complication and standard procedures regarding injection volume and washing-out time of dye should be achieved.

Outcomes of Sentinel Lymph Node-Positive Breast Cancer Patients Treated with Mastectomy Without Axillary Therapy.

Early-stage breast cancer patients with minimal axillary disease identified by sentinel lymph node dissection (SLND) have low regional recurrence rates when treated with breast-conserving surgery and radiation therapy (XRT) and many avoid a completion axillary lymph node dissection (CLND). As the incidence of total mastectomy (TM) has increased, it has become important to characterize which TM patients with a positive SLN may not benefit from further axillary treatment. An institutional database was utilized to identify patients treated with a TM for invasive breast cancer and who had a positive SLN from 1994 to 2010. Clinicopathologic factors were analyzed. Regional recurrence rate, recurrence-free survival (RFS), and overall survival (OS) were determined. A total of 525 patients with invasive breast cancer and a positive SLN were treated with TM, including 58 patients who did not have CLND or XRT and 12 patients who did not have CLND but did receive XRT. Median follow-up was 66months. The incidence of regional recurrence was not significantly different for patients who received no further axillary treatment compared to those who underwent CLND without XRT or those treated with XRT without CLND (10years rate: 3.8 vs. 1.6 and 0% respectively). RFS and OS were not significantly different among patients who received no further axillary treatment compared to those who underwent CLND, XRT, or both. In select patients with early-stage breast cancer treated with mastectomy with a positive SLN, CLND may be avoided without adversely affecting recurrence or survival.

Abstract AL-2: William L. McGuire memorial lecture – Local therapy in the molecular era: Relevant or relic?

Abstract Surgery has always been driven by disease burden; initially, to determine operability, and recently, to select patients for BCT. Systemic therapy also initially relied on disease burden (axillary nodes, tumor size), but gene profiles and molecular targets now predominate in selecting systemic therapy. Reliance on disease burden as a determinant of the intensity of local therapy is problematic as advanced imaging modalities and molecular pathology allow detection of increasingly smaller tumors. The application of management strategies proven beneficial for macroscopic tumor to subclinical disease has the potential for overtreatment as evidenced by increased mastectomy rates in patients undergoing preoperative MRI, and use of ALND and chemotherapy for sentinel node micrometastases. It is an appropriate time to ask how recognition of molecular subtypes and improvements in systemic therapy can be leveraged to improve local therapy outcomes and decrease the burden of therapy. Recognition that systemic therapy results in a major decrease in the rate of IBTR was the major impetus for SSO and ASTRO to commission a systemic review on margins for BCT in stage I and II breast cancer as the evidence base for a consensus conference. We concluded that evidence that margins more widely clear than no ink on tumor significantly improve local control was lacking and the routine practice of obtaining more widely clear margins is not indicated. Adoption of this approach has the potential to spare many women unnecessary surgery. The morbidity of ALND can also be avoided in many patients. The ACOSOG Z0011 trial showed no benefit to ALND for patients with 1 or 2 sentinel node metastases receiving WBRT and systemic therapy. There were many criticisms of this study, but 3 other prospective randomized trials (NSABP B04, NSABP B32, IBCSG 2013) demonstrate that residual axillary nodal disease does not translate to regional recurrence or a decrease in survival in a 1:1 ratio, and that systemic therapy greatly reduces the incidence of regional recurrence. In a prospective study of the applicability of Z0011 findings to an unselected population of women meeting study eligibility criteria, we found that only 16% of 287 consecutive patients had metastases in ≥3 sentinel nodes or matted nodes identified intraoperatively, sparing 84% ALND. These examples represent initial steps in reducing the morbidity of local therapy. Moving forward, it is appropriate to ask whether patients with favorable molecular profiles (luminal A), require the same local therapy as those with other molecular subtypes. More controversially, the success of HER2 blockade in improving survival raises the question of whether effective targeted therapy could allow a reduction in local therapy intensity. A major barrier to progress is the belief of many clinicians and patients that bigger surgery is better surgery. The full realization of multidisciplinary care will occur when improvements in outcomes with one modality result in studies examining the elimination of other treatments which may no longer be beneficial to patients. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr AL-2.

Elective neck dissection vs observation in transorally treated early head and neck carcinomas with cN0 neck

Conclusion: This study showed that elective neck dissection (ND) resulted in reduced regional recurrences in a selected group of surgically treated patients with pT1-2 carcinomas but did not show any benefit for disease-specific survival (DSS). Furthermore, the importance of pN classification was also verified for this patient group. Objectives: The aim of this study was to determine whether the use of elective ND in patients with early head and neck carcinomas and cN0 neck that have undergone a transoral removal of the primary tumor can reduce the incidence of regional recurrence and improve survival. Methods: Between 1980 and 2010, 224 patients that underwent transoral resection of a pT1-2 carcinoma and had a cN0 neck were included in the study; 101 patients received an elective ND and 123 did not. Results: The group that underwent elective ND showed a tendency toward better regional control (RC) (96.0% vs 90.3%, p = 0.07) but similar DSS (85.7% vs 85.4%, p = 0.984). Cases with pN0 classification had a better overall survival (74.6% vs 46.9%, p = 0.07), DSS (88.4% vs 53.6%, p = 0.44), and RC (98.6% vs 62.5%, p < 0.001) compared with pN+ patients.

Analysis of regional recurrence after negative sentinel lymph node biopsy for head and neck melanoma

The head and neck have a rich lymphatic drainage and complex anatomy, which complicate sentinel lymph node (SLN) biopsy for melanoma. The incidence of regional recurrence after a negative SLN biopsy has been shown to be higher than that at other sites. Compounding factors in this scenario were analyzed to determine their impact on both SLN status and survival. A retrospective review of a prospective database of 315 patients who underwent SLN biopsy for head and neck melanoma from 1994 to 2009 was performed. A false-negative SLN biopsy was defined as a regional recurrence in a previously mapped nodal basin. In all, 267 patients (84.8%) were SLN negative (SLN-) and 48 patients (15.2%) were SLN positive (SLN+). The false-negative SLN biopsy occurred in 17 patients (6.4%). The mean follow-up was 37.6 months (3-152 months). The false-negative SLN and SLN+ patients were similar with respect to patient age and sex and primary melanoma tumor thickness and ulceration. The site of the primary melanoma and the lymphatic drainage patterns did not influence the false-negative biopsy rate. The mean survival was SLN- 119.3 months (95% confidence interval [CI], 106.1-132.5, p < .001), SLN+ 73.4 months (95% CI, 52.3-94.4), and the false-negative SLN 70.7 months (95% CI, 54.2-87.1). The risk of a false-negative SLN biopsy in head and neck melanoma is independent of primary site and lymphatic drainage pattern. Patients with head and neck melanoma who have a regional recurrence after a negative SLN biopsy do not have a worse survival than that of patients who are initially SLN positive.

Is dissection of level IV absolutely necessary in elective lateral neck dissection for clinically N0 laryngeal carcinoma?

A prospective study of 73 previous untreated consecutive patients with clinically N0 laryngeal squamous cell carcinoma (SCC) from January 1997 to October 2002 was undertaken to determine whether level IV lymph nodes can be saved in elective lateral neck dissection (LND) performed as a treatment for the N0 neck. The incidence of pathological metastases to level IV lymph nodes was evaluated, as were the incidence of regional recurrence after elective LND, and postoperative complications such as chylous leakage and phrenic nerve paralysis. A total of 142 LNDs were enrolled in this prospective study. The mean number of harvested lymph nodes by level was as follows; 13.1 in level II, 7.1 in level III, and 9.2 in level IV. Pathologic examination revealed nodal involvement in 25 neck specimens (17.6%, 25 of 142). Five necks had lymph nodes which were positive for microscopic metastasis in level IV (3.5%, 5 of 142). These necks were all ipsilateral (6.8%, 5 of 73) and none of the 69 contralateral neck specimens had level IV lymph node metastasis (0%, 0 of 69). With regard to T stage, 3.3% (1 of 30) of ipsilateral necks of T2 tumors exhibited occult metastasis in level IV lymph nodes, 5.9% (2 of 34) for T3 tumors, and 33.3% (2 of 6) for T4 tumors. There were no cases of T1 (n = 3). Separate skip metastasis in level IV lymph nodes was observed in two necks (1.4%, 2 of 142). Four cases of regional recurrence (5.5%, 4 of 73) were observed. Postoperative chylous leakage and phrenic nerve paralysis occurred in four cases (5.5%, 4 of 73) and two cases (2.7%, 2 of 73), respectively. The results of the present study demonstrate the rare incidence of level IV occult lymph node metastasis, as well as infrequent nodal recurrence after elective LND in the treatment of clinically N0 laryngeal SCC. Therefore, dissection of level IV lymph node pads, especially in the ipsilateral neck of early T staged tumors or the contralateral neck, may be unnecessary for the treatment of laryngeal SCC patients with a clinically N0 neck.

Selective neck dissection in the management of the clinically node-negative neck.

To evaluate the efficacy of the selective neck dissection (SND) in the management of the clinically node-negative neck. Case histories were evaluated retrospectively. The results of 300 neck dissections performed on 210 patients were studied. The primary sites were oral cavity (91), oropharynx (30), hypopharynx (16), and larynx (73). Seventy-one necks (23%) were node positive on pathological examination. The number of positive nodes varied from 1 to 9 per side. Of necks with positive nodes, 17 (24%) had extracapsular spread. The median follow-up was 41 months. Recurrent disease developed in the dissected neck of 11 patients (4%). Two recurrences developed outside the dissected field. The incidence of regional recurrences was similar in patients in whom nodes were negative on histological examination (3%) when compared with patients with positive nodes without extracapsular spread (4%). In contrast, regional recurrence developed in 18% of necks with extracapsular spread. This observation was statistically significant. Patients having more than two metastatic lymph nodes had a higher incidence of recurrent disease than the patients with carcinoma limited to one or two nodes. Recurrence rate in the pathologically node positive (pN+) necks was comparable to recurrence in those pathologically node negative (pNO) necks in the patients who did not have irradiation. SND is effective for controlling neck disease and serves to detect patients who require adjuvant therapy.

Squamoid features and expression of involucrin in primary breast carcinoma associated with high histological grade, tumour cell necrosis and recurrence sites.

Although breast carcinomas are considered to originate from glandular epithelial cells, some exhibit 'squamoid features', comprising stratification with a gradient in the nuclear-cytoplasmic ratio within individual cancer cell nests on microscopy. In parallel with a histological review of squamoid features, we immunohistochemically investigated the expression of involucrin, a marker of terminal squamous differentiation, in 223 breast carcinomas with one to three regional nodal metastases but no distant metastases and analysed their association with other clinicopathological parameters to explore their clinical and biological implications. Squamoid features and involucrin expression, detected in 22% and 27% of cases respectively, correlated with each other and were associated with high-grade atypia, a solid-nest pattern, cancer cell necrosis on histology and negative oestrogen receptor status. The incidence of regional recurrences was higher in patients with involucrin expression, whereas bone metastases were less frequent in groups with squamoid features or with diffuse (> or = 10%) involucrin expression. Both squamoid features and involucrin expression, which were considered to be derived either from differentiation into keratinocytes or from some kind of cellular degeneration caused by high turnover rate, are suggested to influence the biological behaviour of breast cancer cells in vivo, and they may be effective in predicting the most likely recurrence sites.

Skin-sparing mastectomy with immediate breast reconstruction: the M. D. Anderson Cancer Center experience.

Skin-sparing mastectomy with immediate reconstruction has become popular with patients because, compared with delayed reconstruction, it improves the cosmetic result, reduces cost and anesthetic risk, and in one stage completes most of the surgical treatment that the patient will ever require for treatment of her breast cancer. In the past, reconstruction was often delayed because of an unwarranted fear of locoregional recurrence or because the patient, having to live for some time with a flat chest wall, would be more appreciative of her reconstruction. This concept is now considered unacceptable, and many women regard this attitude as evidence of a lack of concern for the psychological impact of mastectomy. Provided that the breast skin is not involved with or close to the tumor, we prefer to perform the mastectomy with removal of only the nipple-areolar complex and the tumor biopsy scar. The mastectomy is otherwise the same as a standard modified radical mastectomy with removal of all breast tissue and a level I-II axillary node dissection. Our preference is to use the transverse rectus abdominis myocutaneous flap with a microvascular anastomosis because it provides a better blood supply, reduces abdominal wall muscle sacrifice, and eliminates the bulge from tunneling required by a pedicled flap. Using the skin-sparing technique with immediate reconstruction in 545 patients with early-stage breast cancer, our overall incidence of regional recurrence was 2.6%. Of 95 patients who were followed for > four years, the recurrence rate was 4.2%. Regional recurrence after skin-sparing mastectomy is a function of the biology of the tumor and the stage of the disease and is not affected by the use of immediate reconstruction or skin-preservation mastectomy.

Pulmonary function tests after mantle field irradiation vs. low dose whole lung and mantle field irradiation

In the past, a high incidence of regional recurrence (79%) has been seen in patients with a large mediastinal mass (MT ratio ', .35) following treatment with regular mantle field irradiation. Therefore, since 1975 the mantle field portal utilized in Hodgkin's disease patients with a large mediastinal mass and/or hilar disease has been modified to include low dose (1200-2000 rads) whole lung irradiation. The new approach has resulted in much less regional recurrence (1 out of 15), with minimal follow up time of 24 months (median 53 months). Many questions and concerns arose regarding the changes in lung function after whole lung irradiation compared with the changes in lung function after regular mantle field irradiation alone. The preliminary results of serial pulmonary function tests in two groups of Hodgkin's disease patients will be used to supply some answers to these questions. Group I includes those patients without a large mediastinal mass, and who received regular mantle field irradiation. Group II includes those patients with a large mediastinal mass and/or hilar disease, and who received low dose whole lung irradiation as part of the mantle field. . Serial pulmonary function tests were obtained on seven patients in Group I and on ten patients in Group II. Most of the patients participated in control studies prior to radiotherapy and at two months, six months, twelve months, etc. after treatment with radiotherapy. Each of the control studies consisted of spirometry, lung volumes and arterial blood gases. Changes of lung volumes and mechanics will be compared in preand posttreatment status, and between Groups I and II. The Roentgenographic changes in the lung will also be evaluated by serial chest x-rays.