Risk Factors for Locoregional Failure in Patients With Inflammatory Breast Cancer Treated With Trimodality Therapy

PurposeTo compare patterns of local and regional failure between patients with inflammatory breast cancer (IBC) and non-IBC in patients treated with trimodality therapy.Materials and MethodsWe reviewed records of 463 patients with stage II/III breast cancer, including IBC, who completed trimodality therapy from January 1999 to December 2009.ResultsThe median follow-up was 46.3 months (range, 4-152 months). Clinical stage was 29.4% (n = 136) II, 56.4% (n = 261) non-IBC III, 14.2% (n = 66) IBC, 30.5% (n = 141) cN0/Nx, and 69.5% (n = 322) N1-N3c. All the patients received neoadjuvant therapy and mastectomy (98%, n = 456 with axillary dissection), and all had postmastectomy radiation therapy to the chest wall with or without supraclavicular nodes (82.5%, n = 382) with or without axilla (6%, n = 28). The median chest wall dose was 60.4 Gy. Patients with IBC presented with larger tumors (P < .001) and exhibited a poorer response to neoadjuvant therapy: after surgery, fewer patients with IBC were ypN0 (P = .003) and more had ≥ 4 positive nodes (P < .001). Four-year cumulative incidence of locoregional recurrence was 5.9%, with 25 locoregional events, 9 of which had a regional component. On multivariate analysis, triple-negative disease (hazard ratio [HR] 7.75, P < .0001) and residual pathologic nodes (HR 7.10, P < .001) were associated with an increased risk of locoregional recurrence, but IBC was not. However, on multivariate analysis, the 4-year cumulative incidence of regional recurrence specifically was significantly higher in IBC (HR 9.87, P = .005).ConclusionIn this cohort of patients who completed trimodality therapy, the patients with IBC were more likely to have residual disease in the axilla after neoadjuvant therapy and were at greater risk of regional recurrence. Future study should focus on optimizing regional nodal management in IBC.     

Minimal impact of postmastectomy radiation therapy on locoregional recurrence for breast cancer patients with 1 to 3 positive lymph nodes in the modern treatment era

Introduction

Given modern treatment strategies, controversy remains regarding whether postmastectomy radiation therapy (PMRT) is necessary for breast cancer patients with 1–3 positive axillary lymph nodes (ALN). Our aim was to assess the significance of PMRT in the modern treatment era for these patients.

Inflammatory breast carcinoma: outcomes with trimodality therapy for nonmetastatic disease

BACKGROUND: The objectives of this study were to summarize a single-institution experience in treating patients with inflammatory breast carcinoma (IBC) using trimodality therapy and to identify prognostic factors for outcome. METHODS: Sixty-one women underwent radiation therapy with curative intent for IBC between 1982 and 2001. All but five women received trimodality therapy. Neoadjuvant chemotherapy was given to the majority of women (n = 43 patients), although some received "up-front" surgery as first therapy (n = 18 patients). RESULTS: With a median potential observation time after diagnosis of 14 years, freedom from locoregional disease progression was 78%, freedom from distant metastasis was 45%, and the cause-specific survival rate was 47% at 5 years. Approximately 40% of the 56 patients who received trimodality therapy remained free of disease. Multivariate analysis demonstrated three factors that were found to be associated significantly with improved cause-specific survival: pathologic tumor size < 4 cm (P = 0.0001), up-front surgery (P = 0.0078), and local disease control (P = 0.0003). Factors that were found to be associated with better freedom from locoregional disease progression were pathologic tumor size (< 4 cm; P = 0.0157), age (> 55 years; P = 0.0596), and radiation dose (> or = 60 grays [Gy]; P = 0.0621). CONCLUSIONS: IBC is an aggressive disease that is treated effectively in select patients by multimodality therapy. Patient outcomes may be improved with therapies that result in better local and systemic control. Further studies are warranted to address the optimal sequence of trimodality therapy and the optimal administration of each agent.     

Thoracic Radiation in Limited Stage Small Cell Lung Cancer: Trends in Radiation Fractionation

IntroductionThoracic radiotherapy (TRT) is standard of care for limited-stage small cell lung cancer (LS-SCLC). Although initial data supported the use of twice-daily (BID) radiation to a dose of 45 Gy, recent trials have suggested similar efficacy with daily fractionation (QD) to a dose of 60 to 70 Gy. This study evaluates trends in treatment regimen in patients treated with TRT for LS-SCLC.Materials and MethodsThe National Cancer Database (NCDB) was queried for patients with LS-SCLC treated with TRT between 2004 to 2017 grouped by RT fractionation QD vs. BID. Exclusion criteria were unknown stage, and unknown RT dose. Multivariable (MVA) analyses using logistic regression were performed to investigate factors associated with receipt of a specific fractionation schedule.ResultsA total of 17,453 patients met inclusion criteria, with 4,996 receiving BID treatment and 12,457 receiving QD treatment. The most common QD dose was 60 Gy (48.9%). Overall, QD fractionation has increased (1.3%/year). In 2004, 45 Gy BID treatment (41.4%) was the dominant fractionation. By 2017, 60 Gy QD (45.2%) increased (1.9%/y) to be the dominant fractionation, while 45 Gy BID (24.8%) decreased (-1.4%/y) to be the second most common fractionation. On MVA, factors that affect 1 treatment over the other were further stratified.ConclusionSince 2004, QD fractionation has been the preferred TRT regimen for patients with LS-SCLC compared to BID fractionation, with the proportion of patients getting QD treatment continuing to increase. The choice of treatment regimen appears to be influenced by both patient and facility characteristics.     

皮肤受侵非炎性和炎性乳腺癌的放疗结果

目的 分析现有放疗技术和剂量对皮肤受侵乳腺癌的控制作用.方法 回顾分析53例改良根治术后病理证实为乳腺浸润癌患者资料.其中炎性乳腺癌10例,非炎性乳腺癌43例.非炎性乳腺癌中临床皮肤受侵19例,病理诊断皮肤受侵24例.30例原发肿瘤最大径≤5 cm,13例>5 cm.全组33例接受术后放疗,中位剂量50 Gy,胸壁硅胶填充的6例20 Gy、21例>20 Gy,6例不详.45例行化疗.结果 随访率87%.全组5年局部区域复发率(LRR)、无瘤生存率(DFS)和总生存率(OS)分别为18%、45%和64%.非炎性乳腺癌比炎性乳腺癌有较高的5年DFS(49%:30%;χ2=4.29,P=0.038)和OS(71%:37%;χ2=5.92,P=0.015).非炎性乳腺癌中肿瘤≤5 cm比>5 cm患者有较低的5年LRR(11%:33%;χ2=3.75,P=0.053)和较高的5年OS(90%:38%;x24.44,P=0.035);临床诊断和单纯病理诊断皮肤受侵患者的局部区域复发率、DFS和OS相似.腋窝淋巴结0～3个阳性比≥4个阳性患者有较高的5年DFS(80%:29%;χ2=6.71,P=0.010)和OS(93%:52%;χ2=6.00,P=0.014).Rec+/Her2-比三阴或Her2+患者有较低的5年LRR(7%:34%;χ2=5.70,P=0.017)和较高DFS(54%:32%;χ2=8.82,P=0.003).放疗和未放疗患者的5年LRR分别为12%和30%(χ2=2.45,P=0.118).但放疗患者胸壁硅胶填充剂量>20 Gy和20 Gy患者的5年胸壁复发率为0%和50%(χ2=9.15,P=0.002).结论 皮肤受侵乳腺癌是一组异质性很强的患者,非炎性乳腺癌、原发肿瘤≤5 cm、腋窝淋巴结0～3个阳性和rec+/Her2-患者预后较好.临床诊断和病理诊断皮肤受侵患者的预后无差别.为降低胸壁复发率,胸壁放疗硅胶填充剂量应>20 Gy.     

Preoperative contralateral lung radiation dose is associated with postoperative pulmonary toxicity in patients with locally advanced non-small cell lung cancer treated with trimodality therapy

Purpose

In patients with non-small cell lung cancer (NSCLC) who undergo trimodality therapy (chemoradiation followed by surgical resection), it is unknown whether limiting preoperative radiation dose to the uninvolved lung reduces postsurgical morbidity. This study evaluated whether radiation fall-off dose parameters to the contralateral lung that is unaffected by NSCLC are associated with postoperative complications in NSCLC patients treated with trimodality therapy.

Pulsed reduced dose-rate radiotherapy: a novel locoregional retreatment strategy for breast cancer recurrence in the previously irradiated chest wall,axilla, or supraclavicular region

Purpose Reirradiation of breast cancer locoregional recurrence (LRR) in the setting of prior post-mastectomy radiation poses a significant clinical challenge due to the high risk for severe toxicity. In an attempt to reduce these toxicities, we have developed pulsed reduced dose-rate radiotherapy (PRDR), a reirradiation technique in which a series of 0.2 Gy pulses separated by 3-min time intervals is delivered, creating an apparent dose rate of 0.0667 Gy/min. Here we describe our early experience with PRDR. Patients and methods We reirradiated 17 patients with LRR breast cancer to the chest wall, axilla, or supraclavicular region using PRDR. The median prior radiation dose was 60 Gy. We delivered a median PRDR dose of 54 Gy (range 40–66 Gy) in 1.8–2.0 Gy per fraction. Eight patients received concomitant low dose capecitabine for radiosensitization. The median treatment volume was 2,084 cm³ (range 843–7,881 cm³). Results At a median follow-up of 18 months (range 4–75 months) only 2 patients have had tumor failure in the treatment region. Estimated 2-year local control rate is 92%. Treatment was well tolerated with 4 patients experiencing grade 3 acute skin toxicity. Despite a median cumulative dose of 110 Gy (range 80–236 Gy), there has been only one grade 3 and one grade 4 late toxicity. Conclusions With a median follow-up of 18 months, PRDR appears to be an effective method to reirradiate large volumes of previously irradiated tissue in selected patients with locoregional chest wall, axilla, and supraclavicular recurrences. Presented in part at the 2007 ASCO/ASTRO/ASBS Breast Cancer Symposium, San Francisco, CA, USA, September 7–8, 2007.     

Toxicity and early clinical outcomes in cervical cancer following extended field helical tomotherapy to para-aortic lymph nodes

PurposeTo evaluate toxicity and early disease outcome among patients treated for cervical cancer with extended-field helical tomotherapy to the para-aortic nodes.Patients and methodsThirty-eight patients (International Federation of Gynecology and Obstetrics [FIGO] stage IB2–IVA) from four institutions received extended-field helical tomotherapy and were retrospectively evaluated. All had nodal disease. Para-aortic lymph nodes were involved in 31 patients. Patients were assessed for toxicity using version 4 of the National Cancer Institute's common terminology criteria for adverse events. Survival curves were plotted using Kaplan-Meier estimates.ResultsAll patients underwent radiation to the tumor region (median dose: 45 Gy; range: 44–66 Gy), pelvic lymph nodes and para-aortic lymph nodes (median dose: 45 Gy; range: 44–60 Gy). The median dose to positive lymph nodes was 55 Gy (range: 45–65 Gy). All received platinum-based chemotherapy (31 concurrently). The median follow-up was 15 months. Acute toxicity events observed included one patient with grade 5 febrile neutropenia, 11 patients (29%) with grade 3 hematologic complications. Grades 3–4 gastrointestinal and genitourinary toxicities occurred in six (16%) and four (11%) patients, respectively. Three patients had grade 3 pelvic pain (8%). The 6- and 18-month overall survival rates were 94.7 and 63.9%, respectively. The 18-month locoregional control, disease-free survival, and late grade 3 toxicity rates were 60.2, 43.3 and 7.3%, respectively.ConclusionExtended-field helical tomotherapy was associated with low rates of acute gastrointestinal and genitourinary toxicities with early survival and locoregional control similar to other published series.     

Concomitant boost technique using accelerated superfractionated radiation therapy for advanced squamous cell carcinoma of the head and neck.

Of 142 patients irradiated for American Joint Committee on Cancer Stage III or IV head and neck carcinoma, 100 patients were eligible for analysis with a minimum follow-up of 12 months. In one group, 50 patients were treated with conventional once-a-day (QD) fractionation to doses in excess of 6600 cGy. The other 50 patients were treated prospectively with accelerated superfractionated radiation therapy using a concomitant boost twice-a-day schedule (BID). Patients received conventional fractionation (180 cGy/fraction) combined with a boost field of 160 cGy/fraction BID after a 4-hour to 6-hour interval 3 days per week during part of their treatment course. After 3 years, locoregional tumor control was 62% in the BID group versus 33% in the QD group (P = 0.003). Disease-free survival was 60% and 30%, respectively, for the BID and QD groups (P = 0.002), and adjusted survival was 66% and 38%, respectively, for the BID and QD groups (P = 0.03). Overall survival approached statistical significance in favor of the BID group (P = 0.06). Complete tumor responses were observed in 63% of patients treated in the BID group 1 to 3 months after completion of radiation therapy. Of these, 84% remain free of local recurrence. Of the 19 patients with persistent disease 1 to 3 months after treatment, 47% remain locally controlled. Superfractionated accelerated radiation therapy produced superior local control and disease-free and adjusted survival rates relative to a group of patients treated QD.     

A Prospective Multi-Institutional Phase I/II Trial of Step-Wise Dose-per-Fraction Escalation in Low and Intermediate Risk Prostate Cancer

PurposeThis phase I/II, multi-institutional trial explored the tolerance and efficacy of stepwiseincreasing hypofractionation (HPFX) radiation therapy regimens for fraction sizes up to 4.3 Gy in localized prostate cancer.Methods and MaterialsThree escalating dose-per-fraction schedules were designed to yield similar predicted tumor control while maintaining equivalent predicted late toxicity. HPFX levels I, II, and III were carried out sequentially and delivered schedules of 64.7 Gy/22 fx/2.94 Gy, 58.08 Gy/16 fx/3.63 Gy, and 51.6 Gy/12 fx/4.3 Gy, respectively with next level escalations contingent upon acceptable gastrointestinal (GI) toxicity. The primary endpoints were biochemical control and toxicity.ResultsA total of 347 patients were recruited by 5 institutions with 101, 111, and 135 patients treated on HPFX levels I, II, and III with median follow-ups of 100, 85.5, and 61.7 months, respectively (83.2 months combined). The National Comprehensive Cancer Network low- or intermediate-risk group distribution was 46% and 54%, respectively. Sixteen percent of patients, primarily intermediate risk, received 6 months of androgen deprivation therapy. The 8-year nadir + 2 actuarial biochemical control rates for HPFX levels I, II, and III were 91.1% ± 3.0%, 92.7% ± 2.7%, and 88.5% ± 4.6%, respectively (Kaplan-Meier log rank, 0.903). Among clinical covariates, only Gleason score reached near significance in multivariate analysis (P = .054). Twenty-six patients failed biochemically (crude incidence of 7.5%), and there were 5 cause-specific deaths. GI and genitourinary toxicities were acceptable and similar across the 3 HPFX levels. The combined actuarial cumulative incidence of grade 2+ GI and genitourinary toxicities at 7 years were 16.3% ± 2.1% and 22.1% ± 2.4%, respectively.ConclusionsHPFX employing fraction sizes extending into the 3.6 to 4.3 Gy/fraction range can be delivered with excellent oncologic outcomes. Such schedules, positioned between moderate and ultra-HPFX, may provide additional options for patients wishing to avoid prolonged treatment schedules associated with conventionally fractionated radiation therapy for prostate cancer.     

Advanced head and neck carcinoma in women: treatment outcomes may not improve with accelerated hyperfractionated radiotherapy.

BACKGROUND: The authors undertook a retrospective study on local tumor control, survival, and complications of conventional irradiation compared with accelerated hyperfractionated irradiation in women with selected head and neck tumor sites. METHODS: One hundred eight consecutive women who were treated with radiation alone for cure during 1974-1998 were analyzed. Patients were excluded who had T1 tumors of the vocal cord and those who were treated with brachytherapy implants. Fifty-nine patients were treated with conventional fractionation once daily (QD) during 1974-1998 with a median dose of 2.1 grays (Gy) per fraction up to a total median dose of 69 Gy in a median overall time of 54 days. Forty-nine patients were treated with accelerated hyperfractionation twice daily (BID) during 1987-1998 at a median dose of 1.6 Gy per fraction BID, with an interfraction interval of 4-6 hours, for a total median dose of 66 Gy in 35 days. Patients were not randomized into the QD group or the BID group. RESULTS: The 7-year actuarial local control (LC) rates for T1-T2 tumors in QD-treated and BID-treated patients were 79% and 87%, respectively (P = not significant [NS]). For T3-T4 tumors, the LC rates at 7 years were 59% and 56% for the QD and BID groups, respectively (P = NS). A Cox regression analysis for LC showed that the significant variables were T classification and overall time. Schedule (QD or BID), total dose, dose per fraction, and patient age were not significant variables. For the QD and BID groups, the 7-year actuarial cause specific survival rates for patients with Stage I-II disease were 100% and 65%, respectively (P = 0.004), and, for patients with Stages III-IVA,IVB disease, the rates were 39% and 56%, respectively (P = NS), respectively. Acute morbidity was higher with the BID schedule: In the BID group, 8% of patients required tube or parenteral feeding, and 0% of patients in the QD group required such feeding (P = 0.04). The 5-year actuarial probability of Grade 3-5 late effects (according to the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer grading system) was 4% for the BID group and 0% for the QD group (P = NS). CONCLUSIONS: This study suggests that accelerated hyperfractionated irradiation for women with advanced carcinoma of the head and neck does not provide significantly better local tumor control or cause specific disease free survival compared with conventional fractionation. Women with these malignancies appear to have a better prognosis compared with men.     

Locoregional recurrence risk factors in breast cancer patients with positive axillary lymph nodes and the impact of postmastectomy radiotherapy

Background

Locoregional recurrence (LRR) after mastectomy reduces the patient’s quality of life and survival. There is a consensus that postmastectomy radiotherapy (PMRT) helps establish locoregional control and reduces LRR in patients with ≥4 metastatic nodes. However, in patients with 1–3 metastatic nodes, the incidence of LRR and the role of PMRT have been the subject of substantial controversy. This study assessed the risk factors for LRR and the efficacy of PMRT in Japanese breast cancer patients with metastatic nodes.

Methods

This study analyzed 789 cases of invasive breast carcinoma with metastatic nodes from 1998 to 2008. We divided the study population into 4 groups: 1–3 positive nodes with/without chemotherapy and ≥4 positive nodes with/without chemotherapy. Risk factors for LRR were identified and the relationship between LRR and PMRT was analyzed.

Results

During the median follow-up of 59.6 months, 61 (7.7%) patients experienced LRR. In patients who received chemotherapy, independent LRR risk factors were high nuclear grade, severe lymphatic invasion, vascular invasion, and progesterone receptor-negative status in patients with 1–3 positive nodes, and severe lymphatic invasion and estrogen receptor-negative status in patients with ≥4 nodes. Although patients treated with PMRT had good outcomes, there was no significant difference, and PMRT did not significantly improve the outcome of the patients with all risk factors.

Conclusions

With systemic therapy and adequate dissection, PMRT by itself was of limited value in establishing locoregional control. The indication for PMRT in patients with 1–3 positive nodes remains controversial.     

Implications of constructed biologic subtype and its relationship to locoregional recurrence following mastectomy

Introduction

We examined the prognostic value of biologic subtype on locoregional recurrence (LRR) after mastectomy in a cohort of low risk women who did not receive adjuvant radiation therapy.

Methods

A total of 819 patients with invasive breast cancer underwent mastectomy from January 2000 through December 2005. No patient received preoperative chemotherapy. Estrogen receptor (ER) receptor, progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) status were used to construct the following 4 subtypes: i) ER+ or PR+ and HER2- (HR+/HER2-), ii) ER+ or PR+ and HER2+ (HR+/HER2+), iii) ER- and PR- and HER2+ (HR-/HER2+)and iv) ER- and PR- and HER2- (HR-/HER2-). LRR-free survival was estimated by the Kaplan-Meier method. Cox proportional hazard models were used to evaluate the association between time-to-event outcomes and patient prognostic factors.

Results

At a median follow-up of 58 months, five-year cumulative incidence of LRR for the entire cohort was 2.5%. Subtype specific LRR rates were 1% for HR+/HER2-, 6.5% in HR+/HER2+, 2% for HR-/HER2+ and 10.9% for HR-/HER2- (P < 0.01). In HER-2+ patients (irrespective of ER/PR status), trastuzumab therapy was not associated with LRR-free survival. On multivariate analysis, one to three positive lymph nodes (HR 4.75 (confidence interval (CI) 1.75 to 12.88, P < 0.01), ?? 4 positive lymph nodes (HR23.4 (CI 4.64 to 117.94, P < 0.01), HR+/HER2+ (HR 4.26 (CI 1.05 to 17.33), P = 0.04), and HR-/HER2- phenotype (HR 13.87 (CI 4.96 to 38.80), P < 0.01) were associated with shorter LRR-free survival whereas age > 50 at diagnosis (HR 0.31 (CI 0.12 to 0.80), P = 0.02) was associated with improved LRR-free survival. Among the HR-/HER2- subtypes, five-year LRR incidence was 23.4% in patients with positive lymph nodes compared to 7.8% for lymph node negative patients (P = 0.01), although this association did not reach significance when the analysis was limited to HR-/HER2- women with only one to three positive lymph nodes (15.6% versus 7.8%, P = 0.11).

Conclusions

Constructed subtype is a prognostic factor for LRR after mastectomy among low risk women not receiving adjuvant radiation therapy, although rates of LRR remain low across subtypes. Patients with node positive, HR-/HER2- type tumors were more likely to experience LRR following mastectomy alone. Prospective studies to further investigate the potential benefit of adjuvant radiation therapy in these women are warranted.     

Is post-mastectomy radiation therapy contributive in pN0-1mi breast cancer patients? Results of a French multi-centric cohort

AimTo assess the value of post-mastectomy radiation therapy (PMRT) to breast cancer (BC) patients with no or minimal lymph node (LN) involvement.Materials and methodsWe retrospectively analysed a French multi-centric cohort of 4283 patients treated by mastectomy and axillary dissection, with or without PMRT, between 1980 and 2013. Practices were analysed for three treatment periods (1980–1999, 2000–2005 and 2006–2013). The impact of PMRT on loco-regional recurrence (LRR), disease-free survival (DFS), BC-specific survival and overall survival was assessed in pN0-1mi patients using multivariate analyses (logistic regression and Cox model). It was subsequently assessed based on the number of clinicopathological recurrence-risk factors, generating a prognostic index (French-PMRT index), to isolate a pN0-1mi patients subgroup that might derive a benefit from PMRT. We tested the accuracy of the Cambridge-PMRT (c-PMRT) index to discriminate between patients with significantly different outcomes and the value of PMRT in each c-PMRT prognostic group.ResultsMore than half of the pN0-1mi patients of our cohort underwent PMRT, which almost significantly improved LRR-free survival and DFS. Matching pN0-1mi patients based on the number of clinicopathologic recurrence-risk factors identified a higher risk subpopulation (≥3 recurrence-risk factors), but PMRT did not improve patient outcomes. Although the c-PMRT index had the potential to predict patient outcomes, its use did not help in making the decision of whether or not to use PMRT.ConclusionWe failed to isolate a subgroup of early BC patients without LN involvement suitable for PMRT, despite studying a large cohort.     

Locoregional recurrence risk factors and the impact of postmastectomy radiotherapy on patients with tumors 5 cm or larger

Background

Locoregional recurrence (LRR) after mastectomy reduces the patient’s quality of life and survival. There is a consensus that postmastectomy radiotherapy (PMRT) helps achieve locoregional control and reduces LRR. However, in patients with large tumors, the question of which variables affect the likelihood of LRR and the role of PMRT have been subjects of substantial controversy. This study investigated what the risk factors are for LRR and the efficacy of PMRT in this patient population.

Methods

This retrospective study examined 589 cases of invasive breast carcinoma with tumors 5 cm or larger from 1998 to 2008. We divided the study population into 3 groups: patients with negative nodes, 1–3 positive nodes, and ≥4 positive nodes. The relationship between various clinicopathological variables and LRR was examined, and the relationship between LRR and PMRT was estimated.

Results

During the median follow-up of 44.2 months, 38 (6.5 %) patients experienced LRR. In the multivariate analysis, independent risk factors for LRR included pectoral invasion in patients with 1–3 positive nodes, severity of lymphatic invasion, estrogen receptor-negative status, and a nodal ratio of positive/excised nodes >0.50 in patients with ≥4 positive nodes. In patients without positive nodes, none of the examined variables were significantly associated with LRR. Although patients treated with PMRT had good outcomes, there was no significant difference.

Conclusions

With systemic therapy and adequate lymph node dissection, PMRT by itself was of limited value in establishing locoregional control. Due to the very low incidence of LRR observed, PMRT was not necessary for patients with large tumors without lymph node metastasis. Further examination and consensus about the indications for PMRT in patients with 1–3 metastatic nodes are needed.     

Improved results with accelerated hyperfractionated radiotherapy of advanced head and neck cancer

A retrospective study on local tumor control, survival, and complications of conventional irradiation vs. accelerated hyperfractionated irradiation in patients with selected head and neck cancer sites was undertaken. A total of 1,007 consecutive patients treated with radiation alone for cure from 1974-1997 were analyzed. Excluded were female patients, patients with T1 stage of the vocal cord, and patients also treated with brachytherapy implants. There were 637 patients treated with conventional fractionation once daily (QD) in 1974-1997, at a median 2.1 Gy/fraction, to a total median dose of 71.4 Gy in a median overall time of 54 days. As was common before the mid-1980s, 39% and 22% of patients had overall times exceeding 8 and 9 weeks, respectively; 370 patients were treated with accelerated hyperfractionation twice daily (BID) from 1987-1997, at a median of 1.6 Gy/fraction, with an interfraction interval of 4-6 h, to a total median dose of 68 Gy in 40 days. Both schedules were well-balanced with respect to their pretreatment characteristics. Patients were not randomized into QD or BID. The 10-year actuarial probability of local control was 37% vs. 56% for QD and BID, respectively (P < 0.001), which reflects an increase of 19% or a 51% reduction in the local failure rate. Multivariate analysis revealed that T-stage, QD or BID schedule, and overall treatment time were significant independent factors for achieving local tumor control. The 10-year actuarial probability of cause-specific disease-free survival was 25% and 30% for QD and BID, respectively (P = 0.012). Acute morbidity was slightly higher with the BID schedule: patients requiring tube or parenteral feeding were 2.4% for BID and 0.5% for QD (P = 0.01). The 10-year actuarial probability of RTOG/EORTC Grades 3-5 late effects was 13% for both QD and BID. The lack of increase in late complications was most probably due to the lower total dose and dose per fraction in the BID schedule. This study has shown that accelerated hyperfractionated irradiation using two doses of 1.6 Gy each treatment day for less than 6 weeks in advanced head and neck cancer in male patients provides significantly better local tumor control and cause-specific disease-free survival, without increased late morbidity, than conventional fractionation delivered at the previously relaxed overall times of 7 weeks, but sometimes exceeding 8 or 9 weeks. Int. J. Cancer (Radiat. Oncol. Invest.) 90, 80-91, 2000.     

Effect and Safety of Radiation Therapy Boost to Extramesorectal Lymph Nodes in Rectal Cancer

PurposeIn rectal cancer, the presence of extramesorectal/lateral pelvic lymph node (LPN) is associated with higher risk of locoregional and distant recurrences. LPNs are not typically resected during a standard total mesorectal excision (TME) procedure, and the optimal management for these patients is controversial. We assessed the safety and efficacy of adding a radiation therapy boost to clinically positive LPN during neoadjuvant chemoradiation therapy for rectal cancer.Methods and MaterialsWe analyzed nonmetastatic, lymph node positive rectal adenocarcinoma patients treated with neoadjuvant chemoradiation therapy followed by TME between May 2011 and February 2018. Patients without LPN involvement received external beam radiation therapy (45 Gy in 25 fractions) to the primary tumor and regional draining lymph node basins followed by a boost (5.4 Gy in 3 fractions) to gross disease. Patients with clinically positive LPN that would not be removed during TME received an additional boost (up to a total dose between 54.0 and 59.4 Gy) to the involved LPNs. We compared locoregional control, overall survival, progression-free survival, and treatment-related toxicity between these 2 groups.ResultsFifty-three patients were included in this analysis with median follow-up of 30.6 months for the LPN– group (n = 41) and 19.9 months for the LPN+ group (n = 12). There was no difference in 3-year overall survival (90.04% vs 83.33%, P = .890) and progression-free survival (80.12% vs 80.21%, P = .529) between the 2 groups. We did not observe any LPN recurrences. There were no differences in rates of acute grade 3+ or chronic toxicities.ConclusionsDespite the well-documented negative prognostic effect of LPN metastasis, we observed promising outcomes for LPN+ patients treated with an additional radiation boost. Our results suggest that radiation therapy boost to clinically involved, unresected LPN is an effective treatment approach with limited toxicity. Additional studies are needed to optimize treatment strategies for this unique patient subset.     

Locoregional recurrence rates and prognostic factors for failure in node-negative patients treated with mastectomy: implications for postmastectomy radiation

PURPOSE: Postmastectomy radiation therapy (PMRT) reduces locoregional recurrence (LRR) of breast cancer. Survival appears improved in patients at higher risk for LRR. This study addresses whether subsets of node-negative patients with sufficiently high risk of LRR might benefit from PMRT. METHODS: Retrospective analysis of a cohort of 877 cases of node-negative breast cancer treated with mastectomy, without adjuvant radiation, from 1980 to 2000. RESULTS: Median follow-up was 100 months. Ten-year cumulative incidence of LRR as first event was 6.0%. Size greater than 2 cm, margin less than 2 mm, premenopausal status, and lymphovascular invasion (LVI) were independently significant prognostic factors. Ten-year LRR was 1.2% for those with 0 risk factors, 10.0% for those with 1 risk factor, 17.9% for those with 2 risk factors, and 40.6% for those with 3 risk factors. The chest wall was the site of failure in 80% of patients. CONCLUSION: Postmastectomy radiation therapy has not been recommended for node-negative patients because the LRR rate is low in that population overall. This study suggests, however, that node-negative patients with multiple risk factors, including close margins, T2 or larger tumors, premenopausal status, and LVI, are at higher risk for LRR and might benefit from PMRT. Because the chest wall is the most common site of failure, treating the chest wall alone in these patients to minimize toxicity is reasonable.     

EZH2 expression correlates with locoregional recurrence after radiation in inflammatory breast cancer

Background

Enhancer of zeste homolog 2 (EZH2), a member of the polycomb group proteins, has been shown to promote cancer progression and breast cancer stem cell (CSC) expansion. Breast CSCs are associated with resistance to radiation in inflammatory breast cancer (IBC), a rare but aggressive variant of breast cancer. In this retrospective study, we examined the clinical role of EZH2 in locoregional recurrence (LRR) of IBC patients treated with radiation.

Patients and methods

62 IBC patients who received radiation (7 pre-operative, 55 post-operative) and had adequate follow up to assess LRR were the subject of this study. Positive EZH2 status was defined as nuclear immunohistochemical staining in at least 10% of invasive cancer cells. Association of EZH2 expression with clinicopathologic features were evaluated using the Chi-square statistic and actuarial LRR free survival (LRFS) was determined using the Kaplan-Meier method.

Results

The median follow-up for this cohort was 33.7 months, and the 5-year overall LRFS rate was 69%. Of the 62 patients, 16 (25.8%) had LRR, and 15 out of 16 LRR occurred in EZH2 expressing cases. Univariate analysis indicated that patients who had EZH2-positive IBC had a significantly lower 5-year locoregional free survival (LRFS) rate than patients who had EZH2-negative IBC (93.3% vs. 59.1%; P = 0.01). Positive EZH2 expression was associated significantly with negative ER status (97.1% in ER- vs 48.1% in ER+; P < 0.0001) and triple-negative receptor status (P = 0.0001) and all triple-negative tumors were EZH2-positive. In multivariate analysis, only triple negative status remained an independent predictor of worse LRFS (hazard ratio 5.64, 95% CI 2.19 – 14.49, P < 0.0001).

Conclusions

EZH2 correlates with locoregional recurrence in IBC patients who received radiation treatment. EZH2 expression status may be used in addition to receptor status to identify a subset of patients with IBC who recur locally in spite of radiation and may benefit from enrollment in clinical trials testing radiosensitizers.     

De-escalating Locoregional Therapy for Axillary Micrometastases in Breast Cancer: How Much is Too Much?

BackgroundThe applicability of modern prospective data on adjuvant radiotherapy (RT) fields in patients with micrometastases is limited because many trials occurred prior to routine measurement of nodal metastasis size and modern sentinel lymph node evaluation techniques. We aimed to determine prognostic factors for patients with micrometastases and evaluate the impact of adjuvant RT on disease outcomes.Patients and MethodsPatients diagnosed with pathologic T1-T3 N1mi breast cancers between 2004-2015 were identified. Cox proportional hazards methods were used to determine characteristics predictive of locoregional recurrence (LRR). Tumor and treatment-specific factors were further evaluated using log-rank statistics to compare rates of LRR-free survival.ResultsThis analysis included 156 patients. On multivariable analysis, grade 3 histology (HR 10.84, 95% CI 2.72-43.21) and adjuvant RT (HR 0.22, 95% CI 0.06-0.81) were independent predictors of LRR. Among patients with grade 1-2 histology, 5-year LRR-free survival was 98.8% in patients who received adjuvant RT versus 100% in patients who did not receive adjuvant RT (P = .82). Among patients with grade 3 histology, 5-year LRR-free survival was 90.1% in patients who received adjuvant RT versus 53.0% in patients who did not receive adjuvant RT (P = .025), and 100% in patients receiving comprehensive nodal irradiation versus 76.7% in patients receiving whole breast irradiation or no RT (P = .045).ConclusionPatients with grade 3 micrometastases are at substantial risk for LRR. Adjuvant RT, including comprehensive nodal irradiation, should be strongly considered in these women.