Metastatic esophageal tumors from distant primary lesions: report of three esophagectomies and study of 1835 autopsy cases

Three cases of esophagectomy for secondary esophageal carcinoma metastasized from the ovary, breast and lung are reported. Long-term survival, 14 and 4 years, after esophagectomy was achieved in two patients. The intervals between surgery for primary cancer and dysphagia onset in these two patients were 16 and 7 years, respectively. An aggressive surgical approach appears to be the therapeutic procedure of choice for metastatic esophageal carcinoma when the primary tumor growth rate is suspected to be slow. Autopsy data on 1835 cases revealed 112 (6.1%) had metastasis to the esophagus. The lung was the most common primary tumor-bearing organ and the diffusely infiltrative type was the most common esophageal tumor observed macroscopically which corresponded to the findings in our three patients. When an esophageal stricture with normal mucosa is encountered, a metastatic tumor must be taken into consideration.      

Primary endocrine therapy in locally advanced breast cancers--the Nottingham experience

Introduction There are trials comparing different neoadjuvant chemotherapy regimens for locally advanced primary breast cancer (LAPC). Few studies have evaluated alternative therapeutic approaches towards LAPC. A previous trial from our institute in LAPC patients unselected for oestrogen receptor (ER) status, comparing primary endocrine therapy versus multimodal treatment, showed no difference in breast cancer related deaths or overall survival. We report our experience of primary endocrine therapy in ER+ LAPC. Methods Between 1988 and 2007, 195 ER+, non-inflammatory LAPC patients were treated with primary endocrine agents in our institute, due to patient choice, being unfit for chemotherapy, or recruitment into the above mentioned trial. All patients had disease assessable by UICC criteria. Results Median age was 69 years. The median follow-up was 61 months. 154 patients (79%) received endocrine treatment alone. 185 patients (95%) derived clinical benefit (complete response/ partial response/ stable disease) for ≥6 months from primary endocrine therapy. Overall 5-year survival was 76% and 5-year breast cancer specific survival was 86%. Conclusion In selected group of ER+ LAPC patients, primary endocrine treatment achieves excellent survival outcome and is a viable alternative to other modalities of treatment.     

Whole-brain radiotherapy and tumor bed radiosurgery following resection of solitary brain metastases

A standard approach to solitary brain metastases is resection followed by whole-brain radiation therapy (WBRT). Despite WBRT, the tumor bed remains a common site of failure. We reviewed outcomes following adjuvant WBRT with tumor bed radiosurgery (SRS). We retrospectively identified patients having undergone neurosurgical resection of a single brain metastasis followed by adjuvant WBRT and tumor bed SRS. SRS dose selection was independent of target volume (10 Gy peripheral dose). Outcomes were calculated actuarially. Patients were censured for local control at the time of last imaging. From 2005 to 2008, 27 patients were treated with WBRT and tumor bed SRS. Median age was 58.7 years, median KPS 80%. The primary malignancy was non-small cell lung cancer in 70%. Median follow-up was 9.7 months. Following the combination of surgery, WBRT and SRS the median overall survival was 17.6 months. Actuarial 2-year local control was 94%. The SRS boost was well tolerated with one patient (4%) requiring reoperation for symptomatic radiation necrosis 16 months post treatment. Radiosurgery can be safely added to WBRT as an adjuvant treatment following resection of a single brain metastasis. In our retrospective series, this combination treatment produced a high rate of local control.     

A case of stage IV esophageal cancer successfully treated by chemoradiation

A 63-year-old man was admitted to our institution with a hard tumor on the left side of the neck. He was diagnosed as having advanced esophageal cancer (Stage IV) with a massive supraclavicular lymph node metastasis, and the lesion was thought to be unresectable. He was treated with chemotherapy (CDDP-VDS-5-FU) and radiation therapy, and all the tumors completely disappeared on endoscopic and CT examination. A stricture with scarring was detected in the esophagus at 6 months after treatment. No neoplastic tissue was detected in the lesion, and his dysphagia was relieved by dilation of the stricture. Recurrence on the left side of the neck was detected by CT at 2.5 years after chemoradiation therapy. However, the tumor has not grown over the 2-year interval since then, so it seems to be dormant. He has now survived with a good QOL for 5 years since the first hospital admission. We conclude that advanced esophageal cancer can be treated with chemoradiation therapy if the patient is in sufficiently good overall condition.     

同期腋窝转移淋巴结受体检测在激素受体阴性乳腺癌中的临床意义

  目的   探讨同期腋淋巴结转移病灶雌激素受体（estrogen receptor,ER）和孕激素受体（progesterone receptor,PR）补测在激素受体阴性浸润性乳腺癌中的临床意义。   方法   观察2012年7月至2013年1月,重庆医科大学附属第一医院内分泌乳腺外科门诊随访及住院患者中补测激素受体阴性乳腺癌同期腋淋巴结转移病灶ER和PR的表达情况,所有标本（包括原发癌病灶及同期腋淋巴结转移病灶）的免疫组织化学检测均由重庆医科大学病理检测中心进行,根据检测报告,原发病灶阴性而腋淋巴结转移病灶ER和/或PR阳性者补加内分泌治疗。   结果   56例激素受体阴性乳腺癌中,同期腋淋巴结转移病灶ER阳性8例（14.3%）,PR阳性2例（3.6 %）,ER和PR均阳性3例（5.4%）,共13例（23.3%）因补查腋淋巴结转移病灶ER和/或PR变阳性而在随访中加用内分泌治疗。肿瘤原发病灶与腋转移淋巴结ER和PR均阴性43例（76.7%）,即肿瘤原发癌病灶与腋转移淋巴结ER和PR均为阴性表达的总符合率为76.7%,不一致率为23.3%。   结论   受体阴性浸润性乳腺癌原发病灶与腋淋巴结转移病灶ER和PR表达具有一定的不一致性,对原发癌病灶激素受体阴性乳腺癌患者应检查其同期腋淋巴结转移病灶受体的表达,可能筛查出原发病灶受体阴性而复发转移病灶受体阳性患者,及时加用内分泌治疗,提高该类患者的疗效,亦可解释部分激素受体阴性而内分泌治疗也有一定疗效的原因。      

Primary non-Hodgkin’s lymphoma of the breast treated nonsurgically: report of three cases

Extranodal non-Hodgkin’s lymphoma (NHL) is a rare breast disease. Here we report three cases of primary NHL of the breast. The first patient was a 29-year-old woman with a firm mass in her right breast with ipsilateral axillary lymphadenopathy. An excisional biopsy revealed NHLs. Clinical stage was IIAE. The tumor and enlarged lymph nodes had successfully been treated following the combination therapy. The second patient was a 70-year-old women with an elastic hard mass in her left breast. An excisional biopsy revealed NHLs and clinical stage was 1AE. The tumor disappeared following the combination therapy. The third patient was a 67-year-old women with a hard mass in her left breast. Core needle biopsy revealed NHLs and clinical stage was 1AE. The tumor disappeared following chemotherapy. All patients are alive with no evidence of recurrence 4–8 years after the initial treatment. Although a standard treatment has yet to be established, an initial treatment with combination therapy without surgical intervention including axillary dissection appears to be appropriate for this rare disease.     

The treatment outcome of patients undergoing breast-conserving therapy: the clinical role of postoperative radiotherapy

Background  Treatment outcome was evaluated in patients who underwent breast-conserving therapy and tangential irradiation. After verifying background factors including systemic therapy, the clinical efficacy of postoperative irradiation was investigated. Method  There were 708 study subjects, all of whom had early breast cancer treated between 1992 and 2002. The median follow-up period was 83 months. After breast-conserving surgery, in patients with negative surgical margins, only tangential irradiation at 48 Gy/24 fr was performed. In contrast, in those with positive surgical margins, 10 Gy of radiation boost to the tumor bed with electrons was administered after tangential irradiation with 50 Gy/25 fr. Treatment outcome was analyzed using the Kaplan–Meier method and Cox’s proportional hazards regression model. Results  The disease-free survival and no-recurrence rates within the ipsilateral breast after 5 years were 93.4 and 97.2%, respectively. Risk factors for recurrence within the ipsilateral breast included younger age of patient, the number of positive lymph nodes, and no endocrine therapy. However, the surgical margin was not a risk factor. Risk factors for relapse outwith the ipsilateral breast included younger age, the number of positive lymph nodes, and recurrence within the ipsilateral breast. Conclusions  From our analysis of 708 Japanese women who received breast-conserving therapy, which can be regarded as a standard method in Japan, the treatment outcome was compatible with previous reports from other countries. Presented in part at the 19th meeting of the Japanese Society for Therapeutic Radiation Oncology (JASTRO), 23–25 November 2006, Sendai, Japan.     

Risk of treatment-related esophageal cancer among breast cancer survivors

BackgroundRadiotherapy for breast cancer may expose the esophagus to ionizing radiation, but no study has evaluated esophageal cancer risk after breast cancer associated with radiation dose or systemic therapy use.DesignNested case–control study of esophageal cancer among 289 748 ≥5-year survivors of female breast cancer from five population-based cancer registries (252 cases, 488 individually matched controls), with individualized radiation dosimetry and information abstracted from medical records.ResultsThe largest contributors to esophageal radiation exposure were supraclavicular and internal mammary chain treatments. Esophageal cancer risk increased with increasing radiation dose to the esophageal tumor location (P_trend < 0.001), with doses of ≥35 Gy associated with an odds ratio (OR) of 8.3 [95% confidence interval (CI) 2.7–28]. Patients with hormonal therapy ≤5 years preceding esophageal cancer diagnosis had lower risk (OR = 0.4, 95% CI 0.2–0.8). Based on few cases, alkylating agent chemotherapy did not appear to affect risk. Our data were consistent with a multiplicative effect of radiation and other esophageal cancer risk factors (e.g. smoking).ConclusionsEsophageal cancer is a radiation dose-related complication of radiotherapy for breast cancer, but absolute risk is low. At higher esophageal doses, the risk warrants consideration in radiotherapy risk assessment and long-term follow-up.     

What is the optimal management of dysphagia in metastatic esophageal cancer?

Background

The palliation of dysphagia in metastatic esophageal cancer remains a challenge, and the optimal approach for this difficult clinical scenario is not clear. We therefore sought to define and determine the efficacy of various treatment options used at our institution for this condition.

Methods

We reviewed a prospective database for all patients managed in an esophageal cancer referral centre over a 5-year period. All patients receiving palliation of malignant dysphagia were reviewed for demographics, palliative treatment modalities, complications, and dysphagia scores (0 = none to 4 = complete). The Wilcoxon signed rank test was used to determine significance (p < 0.05).

Results

During 2004–2009, 63 patients with inoperable esophageal cancer were treated for palliation of dysphagia. The primary treatment was radiotherapy in 79% (brachytherapy in 18 of 50; external-beam in 10 of 50; both types in 22 of 50), and stenting in 21%. Mean wait time from diagnosis to treatment was 22 days in the stent group and 54 days in the radiotherapy group (p = 0.003). Mean duration of treatment was 1 day in the stent group and 40 days in the radiotherapy group (p = 0.001). In patients treated initially by stenting, dysphagia improved within 2 weeks of treatment in 85% of patients (dysphagia score of 0 or 1). However, 20% of patients presented with recurrence of dysphagia at 10 weeks of treatment. In the radiotherapy group, the onset of palliation was slower, with only 50% of patients palliated at 2 weeks (dysphagia score of 0 or 1). However, long-term palliation was more satisfactory, with 90% of patients remaining palliated after 10 weeks of treatment.

Conclusions

In inoperable esophageal cancer at our centre, radiation treatment provided durable long-term relief, but came at a high price of a long wait time for initiation of treatment and a long lag time between initiation of treatment and relief of symptoms. On the other hand, endoluminal stenting provided more rapid and effective early relief from symptoms, but was affected by recurrence of dysphagia in the long-term. It is now time for a prospective randomized trial to assess the safety and efficacy of combined-modality treatment with both endoluminal stenting and radiation therapy compared with either treatment alone.     

Radiothérapie exclusive curative chez un patient atteint d’un carcinome bronchique non à petites cellules de stade IV oligométastatique : cas clinique et revue de la littérature

Metastatic non-small cell lung cancer is associated with a poor prognosis, and palliative chemotherapy is the mainstay of treatment. However, long-time survival has been observed in oligometastatic patients treated with locally ablative therapies to all sites of metastatic disease. An 80-year-old man was diagnosed with an adenocarcinoma of the lung. The right upper lobe lesion was classified cT2aN0M0 and was treated with stereotactic body radiation therapy at the dose of 60 Gy in eight fractions. A few months after, he successively presented with two brain metastases and one left adrenal metastasis, with a complete response on the primary tumor. The three secondary lesions were treated with stereotactic body radiation therapy alone. Thirty months after the diagnosis and 12 months after metastases’ apparition, primary and brain lesion kept controlled (complete response). Oligometastatic non-small cell lung cancer management is not clear. Locally ablative therapies such as stereotactic body radiation therapy, surgery and radiofrequency are efficient and should be considered. A phase III study should evaluate radical treatment strategies in such patients.     

Strategy of radiation therapy for bone metastases and MSCC in breast cancer patients

Bone metastasis is a common event in advanced cancers such as prostate, breast, lung, and renal cancers. Radiation therapy has been widely used for bone metastasis. However, it remains a challenging therapy because no radiation therapeutic guidelines, including radiation dose, radiation field, and fractionation, for patients with bone metastasis have been established. Many randomized controlled trials for bone metastasis have been carried out. They showed no significant difference in pain relief with a short course of radiation therapy such as 8 Gy/1 Fr and 20 Gy/5 Fr or with a long course of radiation therapy such as 30 Gy/10 Fr, 37.5 Gy/15 Fr, and 40 Gy/20 Fr. Toxicity rates with short and long courses were also the same. Recurrence rate at 2 years, however, was significantly higher in patients irradiated with a short course than in patients irradiated with a long course. Those trials also showed that response rate is affected by patient’s age, performance state, tumor type, pathological state, number of metastatic tumors, and span from diagnosis of cancer to development of metastatic tumor. Breast cancer has a better prognosis than most other cancers. Recently, there have been significant advances in cancer therapy techniques and improvement in clinical results. Bone metastasis can cause extreme pain and motor deficits. Quality of life for patients with bone metastasis is drastically worsened. Patients with bad prognosis should be treated with radiation therapy when analgesia is the main aim of treatment. Survival of patients with oligometastasis or predominantly bone metastasis is expected to be better than that of patients with visceral metastasis. For patients with vertebral or weight-bearing long bone metastasis, long-course therapy is recommended. Many patients who are expected to have a good prognosis should be treated with a long course of radiation.     

结直肠癌肝转移的新辅助治疗进展

目前,新辅助治疗已逐步应用到结直肠癌肝转移的治疗模式中.临床研究表明,新辅助化疗、新辅助放疗和新辅助放化疗可提高结直肠癌肝转移的手术切除率和根治性,对中下段直肠癌可术前降期、提高手术切除率、保肛率和降低复发率.新辅助治疗在结直肠癌肝转移综合治疗中具有较大的临床应用价值.     

Serum CD44 levels and overall survival in patients with HER2-positive breast cancer

CD44 is an adhesion molecule involved in tumor cell invasion and metastasis. The function of CD44 in breast cancer is not understood completely, or is its role as a predictive or prognostic factor. In this study, we tested for the hypothesis that the concentration of soluble CD44 (sCD44) in serum is correlated with clinicopathological factors, especially HER2, and survival in patients with breast cancer. We retrospectively identified 110 patients with breast cancer who had been treated at The University of Texas MD Anderson Cancer Center (MDACC) from September 2001 to May 2004. Sera were collected before definitive surgery in patients with stage I or II breast cancer, before initiation of neoadjuvant chemotherapy (if indicated) for patients with stage I–III breast cancer, and before initiation of systemic therapy in patients with stage IV breast cancer. sCD44 levels were determined using an enzyme-linked immunosorbent assay. The median age at diagnosis was 51 years (range, 28.6–87.1 years). sCD44 concentration was correlated with tumor stage (P = 0.0308). sCD44 serum concentration did not predict pathological response in patients treated with neoadjuvant chemotherapy. Among patients with distant metastases, sCD44 levels were significantly higher in patients with liver involvement than in patients with metastases at other sites. The overall survival rate did not differ between patients with high sCD44 concentration and patients with low sCD44 concentration. However, sCD44 concentration was a significant predictor of overall survival for patients with HER2-positive breast cancer, while no difference in overall survival rates was observed in patients with HER2-negative breast cancer. To the best of our knowledge, this is the first study to show an association between circulating sCD44 levels and survival in HER2-positive breast cancer patients. Our results suggest a role for sCD44 as a prognostic marker. Furthermore, sCD44 level may offer a new clinical therapeutic target in HER2-positive breast cancer.     

The influence of travel time on breast cancer characteristics, receipt of primary therapy, and surveillance mammography

Travel time has been shown to influence some aspects of cancer characteristics at diagnosis and care for women with breast cancer, but important gaps remain in our understanding of its impact. We examined the influence of travel time to the nearest radiology facility on breast cancer characteristics, treatment, and surveillance for women with early-stage invasive breast cancer. We included 1,012 women with invasive breast cancer (stages I and II) who had access to care within an integrated health care delivery system in western Washington State. The travel times to the nearest radiology facility were calculated for all the U.S. Census blocks within the study area and assigned to women based on residence at diagnosis. We collected cancer characteristics, primary and adjuvant therapies, and surveillance mammography for at least 2.5 years post diagnosis and used multivariable analyses to test the associations of travel time. The majority of women (68.6%) lived within 20 min of the nearest radiology facility, had stage I disease (72.7%), received breast conserving therapy (68.7%), and had annual surveillance mammography the first 2 years after treatment (73.7%). The travel time was not significantly associated with the stage or surveillance mammography after adjusting for covariates. Primary therapy was significantly related to travel time, with greater travel time (>30 min vs. ≤ 10 min) associated with a higher likelihood of mastectomy compared to breast conserving surgery (RR = 1.53; 95% CI, 1.16–2.01). The travel time was not associated with the stage at diagnosis or surveillance mammography receipt. The travel time does seem to influence the type of primary therapy among women with breast cancer, suggesting that women may prefer low frequency services, such as mastectomy, if geographic access to a radiology facility is limited.     

Early gastric cancer combined with multiple metachronous osteosclerotic bone and bone marrow metastases that responded to chemoradiotherapy

We report a 75-year-old woman who suffered multiple metachronous osteosclerotic bone metastases 4 years after a distal gastrectomy for early gastric cancer (EGC). The primary tumor was a poorly differentiated adenocarcinoma, which had invaded the submucosal layer, and only one lymph node metastasis was noted. To the best of our knowledge, cases of EGC combined with metachronous osteosclerotic multiple bone and bone marrow metastases that respond to chemoradiotherapy are very rare. In this case, the multiple bone metastases were diagnosed 4 years after surgery. The patient’s metastatic tumor was successfully treated using S-1, paclitaxel, and camptothecin, with subsequent irradiation. The patient survived for 24 months after the treatment, without having any major symptoms.     

首发腋窝淋巴结转移瘤26例临床分析

 目的　分析首发腋窝淋巴结转移瘤的临床特征。方法　分析 2 6例以腋窝肿块为首发的恶性转移瘤患者的发病情况、肿块特征、诊断、治疗效果等。结果　以腋窝肿块为首发的恶性转移瘤患者中 (不包括淋巴瘤 ) ,最常见的分别是乳腺癌、黑色素瘤、肺癌 ,肿块大小不等、质硬、或与皮肤粘连 ,如果无广泛转移 ,采取切除原发瘤及转移瘤的以手术治疗为主的综合治疗。结论　腋窝淋巴结转移瘤以乳腺癌、黑色素瘤、肺癌多见 ,应采取综合治疗 ,预后较差     

Second cancers in patients with male breast cancer: a literature review

Purpose  The risk of second malignancies among female breast cancer patients has been studied for decades. In contrast, very little is known about second primary tumors in men. Risk factors for breast cancer in men, including genetic, hormonal and environmental factors, provide parallels to the etiology of breast cancer in women. This review considers the literature related to the risk of developing a second cancer in patients with male breast cancer. Materials and methods  A systematic review of the literature between 1966 and 2007 was conducted and acceptable articles used for analysis. All retrieved articles were screened to identify any papers that had been missed. Studies were included if they discussed the risk of subsequent malignancy in patients with male breast cancer. Results  Patients with history of male breast cancer have an increased risk of a second ipsilateral, or contralateral breast cancer (standardized incidence ratio 30–110). The risk of subsequent contralateral breast cancer was highest in men under 50 years of age at the time of the diagnosis of the initial cancer. The data on non-breast second primary cancers is diverse. One study has suggested an increased incidence of cancers of the small intestine, prostate, rectum and pancreas, and of non-melanoma skin cancer and myeloid leukaemia. Other investigators did not find an increase in the overall risk of subsequent cancer development in men diagnosed initially with primary breast cancer. Although sarcoma, lung and esophageal cancers are well recognized complications of radiation therapy for female breast cancer, there is no evidence for the association of these cancers following radiation therapy in male breast cancer. Conclusions  Although the incidence of second primary cancer in patients with primary male breast cancer requires further study, male breast cancer survivors should probably undergo periodic screening for the early detection of second breast cancers and other adverse health effects.     

A case of HER-2-positive advanced inflammatory breast cancer with invasive micropapillary component showing a clinically complete response to concurrent trastuzumab and paclitaxel treatment

We report a case of HER-2-positive advanced inflammatory breast cancer with invasive micropapillary component showing a complete response to trastuzumab and paclitaxel treatment. A 37-year-old woman was referred to our hospital for right breast swelling with broad skin redness and right axillary tumor. Ipsilateral infraclavicular and contralateral axillary lymph nodes swelling were also recognized. The histopathological findings of core-needle biopsy specimens from primary breast tumor and ipsilateral axillary lymph node were invasive ductal carcinoma with a micropapillary component. Immunohistochemical examination gave a negative result for estrogen receptor (ER)/progesterone receptor (PgR), and overexpression of HER-2 (Hercep Test 3+). Advanced inflammatory breast cancer with an invasive micropapillary component was diagnosed (T4d N3 M1 (LYM), stage IV). The patient was treated with combination chemotherapy using weekly paclitaxel and trastuzumab. After administration of three courses, the breast swelling, skin redness, and lymph node swelling disappeared completely. She maintained complete remission of disease for 12 months and was judged to have a clinically complete response by the RECIST criteria. Invasive micropapillary carcinoma is known to be an aggressive histological type associated with a high incidence of lymph node metastasis and poor prognosis. This is the first reported case of advanced inflammatory breast cancer with an invasive micropapillary component showing a clinically complete response to trastuzumab-containing treatment. This report suggests trastuzumab-containing chemotherapy is a promising therapy for HER-2-positive advanced invasive micropapillary carcinoma.     

Patterns of recurrence of early breast cancer according to estrogen receptor status: a therapeutic target for a quarter of a century

The current therapeutic strategy in breast cancer is to identify a target, such as estrogen receptor (ER) status, for tailoring treatments. We investigated the patterns of recurrence with respect to ER status for patients treated in two randomized trials with 25 years’ median follow-up. In the ER-negative subpopulations most breast cancer events occurred within the first 5–7 years after randomization, while in the ER-positive subpopulations breast cancer events were spread through 10 years. In the ER-positive subpopulation, 1 year endocrine treatment alone significantly prolonged disease-free survival (DFS) with no additional benefit observed by adding 1 year of chemotherapy. In the small ER-negative subpopulation chemo-endocrine therapy had a significantly better DFS than endocrine alone or no treatment. Despite small numbers of patients, “old-fashioned” treatments, and competing causes of treatment failure, the value of ER status as a target for response to adjuvant treatment is evident through prolonged follow-up.     

A case of esophageal cancer with intramural metastasis demonstrates a good clinical course after induction chemotherapy followed by chemoradiation

A 63-year-old man with dysphagia visited our hospital in February 2007. Esophagogastroduodenoscopy and computed tomography revealed that he suffered from advanced esophageal cancer with intramural metastasis at clinical stage III (T3N1). The patient underwent induction chemotherapy because he had great difficulty deciding which treatment would be more beneficial for him use dash surgery or chemoradiation. The reason for his in decision was that esophageal cancer with intramural metastasis is known to have a poor prognosis after surgery, and although chemoradiation is the more attractive therapy that avoids invasive surgery, it is very difficult to predict a response. Currently, he has survived for more than 3 years with no recurrence, after chemoradiation that followed a good response to induction chemotherapy. This result suggested that induction chemotherapy followed by chemoradiation can be one of the useful strategies for patients who have esophageal cancer with a negative prognosis factor for surgery, such as intramural metastasis.