Adjuvant chemo-immunotherapy in stage II carcinoma of the breast

From July of 1974 to June of 1978, 131 patients with Stage II carcinoma of the breast were randomly assigned to one of three treatment arms in order to assess the efficacy of adding immunotherapy to adjuvant chemotherapy. All patients had metastases in the axillary lymph nodes, but no clinical evidence of systemic disease. Prognostic factors were relatively equally distributed among the three treatment arms. All patients received adjuvant chemotherapy consisting of cytoxan, methotrexate, and 5-fluorouracil (CMF). In addition, patients received adjuvant immunotherapy consisting of Bacille Calmette Guerin (BCG) or BCG plus a tumor cell vaccine. This vaccine was a mixture of allogeneic breast cancer cell lines grown in tissue culture. Fourteen patients receiving tumor cell vaccine developed hepatitis B, leading to the abandonment of this arm of the study. Side effects of chemotherapy were tolerable. No statistically significant difference could be demonstrated in recurrence rate or survival. However, the two groups receiving adjuvant chemo-immunotherapy had a slightly shorter time to recurrence and lower overall survival. The use of chemo-immunotherapy as administered in this study did not improve the clinical course of patients with Stage II breast cancer and was associated with significant morbidity.     

Multimodal approach in the therapy of stage III female breast cancers

One thousand thirty-seven female breast cancers were treated at the Cancer Institute (WIA), Madras, between 1965 and 1978. Five hundred twenty-one of them (ie, just over 50%) were in stage III, with extensive local disease, unsuitable for surgery ab initio. Four hundred twelve of them (group A) received radiation therapy (RT) initially and 109 (group B) a combination of radiation and chemotherapy (CT). In 68% of the former and 77% of the latter the tumours became resectable after this preliminary treatment. Radical mastectomy in group A and Patey's mastectomy in group B were performed. The material in these two groups was similar. The five-year survival NED in group A was 45%, and in group B 64.61%. Adequate surgery following RT and CT seemed essential to improve survival. The impact of added chemotherapy (CT) was mainly felt in the node-positive cases.     

Adjuvant chemotherapy for stage III colon cancer in the oldest old

BACKGROUND:

Randomized trials demonstrating the benefits of chemotherapy in patients with American Joint Committee on Cancer stage III colon cancer underrepresent persons aged ≥ 75 years. The generalizability of these studies to a growing elderly population remains unknown.

METHODS:

Using the California Cancer Registry for 1994 through 2008, the authors conducted a population‐based study of postcolectomy patients aged 50 years to 94 years with stage III (N1M0) colon adenocarcinoma. A 2‐sided chi‐square test and Cochran‐Armitage test for trend were used to compare patient and tumor characteristics associated with receipt of chemotherapy across age groups. Multivariate regression was used to assess the association between older age and receipt of chemotherapy. Kaplan‐Meier methods and Cox proportional hazards modeling were used to evaluate the association between chemotherapy and mortality, with propensity score adjustment.

RESULTS:

Approximately 44% (12,382 patients) of the study cohort was aged ≥ 75 years. Persons aged ≥ 75 years were found to be less likely to have received adjuvant chemotherapy than those aged < 75 years (30% vs 68% in patients aged 50 years‐74 years; P < .0001). On multivariate analysis, patients aged 75 years to 84 years were 13 times less likely, and those aged 85 years to 94 years were 24 times less likely, to have received chemotherapy as patients aged 50 years to 64 years. Nevertheless, age‐stratified multivariate survival analyses indicated that chemotherapy provided comparable mortality reduction across age groups.

CONCLUSIONS:

The percentage of persons aged ≥ 75 years receiving adjuvant chemotherapy remains low despite demonstrated survival benefits. These findings deserve attention within the context of a patient's life expectancy, underlying comorbidities, and performance status, as well as clinician bias. The results of the current study support the call for phase II/III studies assessing the toxicities and benefits of adjuvant chemotherapy for the treatment of stage III colon cancer in the elderly. Cancer 2013. © 2012 American Cancer Society     

早期乳腺癌的诊断体会

目的　探讨发现早期乳腺癌的方法。方法　对 1997年至 1999年我院收治的 192例乳腺癌 ,进行回顾性研究。结果　其中早期乳癌 10例 ,占同期收治乳癌总数的 5 .2 %( 10 /192 )。其中T0癌 4例 ,肿块 <0 .5cm的微小癌 6例 ,有乳腺癌易患因素者 5例 ,有乳头溢液者 3例 ,有乳房局灶增厚者 1例 ,伴乳腺增生症者 3例 ,3例是在例行健康检查时发现的。结论　 ( 1)提高对早期乳腺癌的认识 ,“乳腺癌≠乳腺肿块” ;( 2 )普及防癌知识 ,提倡健康检查 ;( 3)重视早期乳腺癌的临床特点 ;( 4 )提倡多种诊断方法联合应用 ,取长补短 ,综合分析。     

The clinical significance of lymph node micrometastasis in stage I and stage II colorectal cancer

Aim Recent advances in immunohistochemical techniques have made it possible to identify micrometastasis using antibodies to cytokeratins (CK). The aim of the study was to determine the prevalence and prognostic significance of immunohistochemically detected micrometastasis (IHM) in patients with localised colorectal cancer (CRC) (Dukes’ A and B). A further aim was to study the prognostic role of histopathological factors such as vascular invasion. Methods The original histology of 168 consecutive patients with Dukes’ A or B tumours who had undergone curative resection was reviewed. Immunohistochemical staining was performed using CK antibodies, AE1/AE3 and MNF116 on all (n=898) lymph nodes. Survival analysis was performed on 105 cases that had been followed up until death or for at least 5 years. Results IHM were detected in 17.3% of lymph nodes analysed. Adverse outcome (death/local recurrence) was recorded in 8/49 (16%) patients with IHD-positive nodes and in 10/56 (18%) patients negative for IHM. IHM was not associated with adverse outcome on either univariate (p=0.540) or multivariate analyses (p=0.673). There was no correlation of IHM with age, gender, site, size and grade of tumour, depth of tumour invasion or perineural and vascular invasion. Vascular invasion was the only independent prognostic factor identified. Discussion We have shown that isolated CK-positive epithelioid cells are commonly found in morphologically benign pericolic lymph nodes of patients with localised (Dukes’ A or B) CRC. These cells may represent occult micrometastasis but are not clinically significant. Vascular invasion identifies patients with localised CRC likely to develop recurrences or die of disease. Presented to Royal Australasian College of Surgeons annual meeting, Adelaide (2002) and Association of Coloproctology of GB and Ireland, annual meeting, Manchester, UK (2002)     

Novel combination of serum microRNA for detecting breast cancer in the early stage

MicroRNA (miRNA), which are stably present in serum, have been reported to be potentially useful for detecting cancer. In the present study, we examined the expression profiles of serum miRNA in several large cohorts to identify novel miRNA that can be used to detect early stage breast cancer. We comprehensively evaluated the serum miRNA expression profiles using highly sensitive microarray analysis. A total of 1280 serum samples of breast cancer patients stored in the National Cancer Center Biobank were used. In addition, 2836 serum samples were obtained from non‐cancer controls, 451 from patients with other types of cancers, and 63 from patients with non‐breast benign diseases. The samples were divided into a training cohort including non‐cancer controls, other cancers and breast cancer, and a test cohort including non‐cancer controls and breast cancer. The training cohort was used to identify a combination of miRNA that could detect breast cancer, and the test cohort was used to validate that combination. miRNA expressions were compared between patients with breast cancer and non‐breast cancer, and a combination of five miRNA (miR‐1246, miR‐1307‐3p, miR‐4634, miR‐6861‐5p and miR‐6875‐5p) was found to be able to detect breast cancer. This combination had a sensitivity of 97.3%, specificity of 82.9% and accuracy of 89.7% for breast cancer in the test cohort. In addition, this combination could detect early stage breast cancer (sensitivity of 98.0% for Tis).     

早期乳腺癌诊断的临床分析

目的：探讨早期乳腺癌的临床诊断方法。方法：对482例乳腺癌患者的诊治过程进行回顾性分析。结果：乳腺钼靶与彩超联合检查易发现早期乳癌。结论：乳腺普查可以发现无临床症状的早期乳癌患者。     

Usefulness of preoperative CEA levels in the assessment of colorectal cancer patient stage

In order to demonstrate a prognostic value of preoperative CEA levels, we have tried to define a correlation between CEA and histologic stage of tumor in 124 patients with colorectal carcinoma. CEA concentration has been evaluated by radioimmunologic assay and the histologic stage following Dukes' classification. The results show a 25.0% positivity rate for patients in stage A, 48.2% for stage B, 61.1% for stage C, and 85.7% for stage D. The mean CEA values are 7.8 ng/ml in the first group, 30.3 ng/ml in the second, 58.1 ng/ml in the third, and 134.3 ng/ml in the last group. Furthermore, we have tried to relate the histopathologic grade of the tumor (G) with CEA levels in 54 patients of the 124. We conclude that preoperative CEA has a prognostic value, and it is useful in the staging of colorectal cancer patients. A low concentration indicates an early stage of the tumor, while a high concentration indicates a wide spread of disease; on the other hand, there are not significant correlations with cancer grading.     

Laparoscopy significantly improves the perceived preoperative stage of gastric cancer

Background The aim of this study was to examine the accuracy of laparoscopy in staging patients with gastric cancer in comparison with preoperative computed tomography (CT) examination.Methods One hundred patients out of a consecutive series of 258 patients with gastric adenocarcinoma underwent a preoperative staging CT followed by a staging laparoscopy. The strengths of the agreement between the CT stage, the laparoscopic stage, and the final histopathological stage were determined by the weighted Kappa statistic (Kw).Results The strengths of agreement between the CT stage and the final histopathological stage were Kw = 0.336 (95% confidence interval [CI]; 0.172–0.5; P = 0.0001) for T stage and 0.378 (95% CI; 0.226–0.53; P = 0.0001) for M stage, compared with 0.455 (95% CI; 0.301–0.609; P = 0.0001) and 0.73 (95% CI; 0.596–0.864; P = 0.0001) for the laparoscopic T and M stages, respectively. Unsuspected metastases that were not detected by CT, were found in 21 patients at laparoscopy, all of whom had T3 or T4 locally advanced tumors evident on CT.Conclusions Preoperative laparoscopic staging of gastric cancer is indicated for potential surgical candidates with locally advanced disease in the absence of metastases on CT.An original article presented at The British Society of Gastroenterology, Birmingham, 2002 (Gut 2002; 50 [Suppl. II] A8).     

Survival following orchiectomy for stage D adenocarcinoma of the prostate

The survival of nonprivate and private patients following orchiectomy for stage D adenocarcinoma of the prostate was studied. While the private patients enjoyed a longer survival, their improved survival was found to be a function of an earlier presentation. Examination of the survival statistics with linear regression analysis suggested that survival following orchiectomy is a function of the age at the time of orchiectomy.     

Prognosis of segmentectomy in the treatment of stage IA non-small cell lung cancer

With improvements in detection technology, increasing numbers of patients with non-small cell lung cancer (NSCLC) are being diagnosed at an early stage. In order to treat the illness with minimal invasion and preserve lung function to the greatest possible extent, there has been an increasing tendency towards treating early-stage NSCLC by segmentectomy. However, questions remain regarding whether patients may benefit from this procedure considering the surgical and oncological outcomes. Whether adequate margin distance and lymph node dissection may be achieved is one of the most important issues associated with this procedure. The present study reviews the prognosis of segmentectomy in the treatment of stage IA NSCLC.     

Chromosomal alterations in the clonal evolution to the metastatic stage of squamous cell carcinomas of the lung

Comparative genomic hybridization (CGH) was applied to squamous cell carcinomas (SCC) of the lung to define chromosomal imbalances that are associated with the metastatic phenotype. In total, 64 lung SCC from 50 patients were investigated, 25 each with or without evidence of metastasis formation. The chromosomal imbalances summarized by a CGH histogram of the 50 cases revealed deletions most frequently on chromosomes 1p21-p31, 2q34-q36, 3p, 4p, 4q, 5q, 6q14-q24, 8p, 9p, 10q, 11p12-p14, 13q13-qter, 18q12-qter and 21q21. DNA over-representations were most pronounced for chromosomes 1q11-q25, 1q32-q41, 3q, 5p, 8q22-qter, 11q13, 12p, 17q21-q22, 17q24-q25, 19, 20q and 22q. In ten cases, paired samples of primaries and at least one metastasis were analysed. The comparison revealed a considerable chromosomal instability and genetic heterogeneity; however, the CGH pattern indicated a clonal relationship in each case. The difference in histograms from the metastatic and non-metastatic tumour groups was most useful in pinpointing chromosomal imbalances associated with the metastatic phenotype, indicating that the deletions at 3p12-p14, 3p21, 4p15-p16, 6q24-qter, 8p22-p23, 10q21-qter and 21q22, as well as the over-representations at 1q21-q25, 8q, 9q34, 14q12 and 15q12-q15, occurred significantly more often in the metastatic tumour group. The comparison of the paired samples confirmed these findings in individual cases and suggested distinct genetic changes, in particular the extension of small interstitial deletions, during tumour progression. Importantly, metastasis-associated lesions were frequently detectable in the primary tumour providing a method of identifying patients at risk for tumour dissemination. Individual profiles and histograms are accessible at our web site http://amba.charite.de/cgh.     

Controversies in the management of stage III non-small-cell lung cancer

Lung cancer remains the leading cause of death in the USA and is the most common cancer both in incidence and in mortality globally (1.35 million deaths annually). Non-small-cell lung cancer accounts for >80% of all lung cancers . About 35–45% of non-small-cell lung cancer patients present with locally advanced non-metastatic stage III disease. However, confirmed stage III disease represents a very heterogeneous group ranging from borderline surgical candidate with minimal mediastinal involvement to bulky mediastinal nodes or contralateral nodal involvement with significant controversy regarding optimal management in these various situations. This article specifically addresses the role of surgery, radiotherapy and chemotherapy in multimodal approach to treat stage III patients with N2/N3 involvement and controversies surrounding these recommendations.     

Resection of the primary tumor in stage IV breast cancer

Stage IV breast cancer refers to breast cancer that has already metastasized to distant regions when initially diagnosed. Treatment for stage IV is intended to “prolong survival and palliate symptoms”. Resection of a primary tumor is considered to be “effective only at alleviating chest symptoms and providing local control” in spite of the advances of imaging examination and medication for breast cancer. Molecular target and endocrine drugs are very effective and useful to tailor-make a treatment strategy according to breast cancer subtypes. Positron emission tomography-computed tomography can detect and diagnose the very small metastases and recurrences which can potentially be cured even if they are distant metastases. Recently, many retrospective studies have reported the survival benefit of surgery for breast cancer patients with metastases and some clinical trials which confirm the surgical prognostic benefit for them have started to enrol patients. The goal of treatment has to be clearly identified: increase the patient’s survival time, provide local control or perform histology to determine the cancer’s properties. The best evidence is absolutely essential to treat patients who need surgery at the right time. We need to evaluate the treatment strategy, including primary resection for stage IV breast cancer particularly, and find new evidence by prospective analysis.     

Cost of managing women presenting with stage IV breast cancer in the United Kingdom

This study estimated lifetime cost of treatment for patients in the United Kingdom (UK) presenting with stage IV breast cancer. To determine patterns of treatment and resource use in the absence of direct observational data, a cancer physician panel was surveyed. The survey questionnaire described four predefined treatment phases: active treatment; follow-up after active treatment until disease progression; active supportive care after progression; and end-of-life care. Physicians were asked their major treatment strategies for each phase. Monthly cost and average lifetime cost per patient were calculated. Only five cancer registries in the UK document the proportion of breast cancer patients diagnosed with stage IV disease. Their data was used to estimate the incidence of metastatic breast cancer at presentation throughout the UK. This value, together with lifetime cost per patient and projected survival time, allowed approximation of the overall cost for this population of cancer patients in the UK. Annual incidence of stage IV breast cancer at presentation in the UK is approximately 2100; according to treatment practice in 2002, lifetime cost per patient is pound 12 500 and total population cost is approximately pound 26 million. The substantial economic burden associated with patients diagnosed with metastatic breast cancer should be considered when developing strategies for reducing its incidence such as increased awareness, screening and preventative measures.     

Impact of smoking on patients with stage III colon cancer

BACKGROUND:

Cigarette smoking has been shown to increase the risk of developing colorectal cancer, particularly smoking early in life. Little is known about the impact of tobacco use on colon cancer recurrence among colon cancer survivors.

METHODS:

The authors prospectively collected lifetime smoking history from stage III colon cancer patients enrolled in a phase 3 trial via self‐report questionnaires during and 6 months after completion of adjuvant chemotherapy. Smoking status was defined as never, current, or past. Lifetime pack‐years were defined as number of lifetime packs of cigarettes. Patients were followed for recurrence or death.

RESULTS:

Data on smoking history were captured on 1045 patients with stage III colon cancer receiving adjuvant therapy (46% never smokers; 44% past; 10% current). The adjusted hazard ratio (HR) for disease‐free survival (DFS) was 0.99 (95% confidence interval [CI], 0.70‐1.41), 1.17 (95% CI 0.89‐1.55), and 1.22 (95% CI 0.92‐1.61) for lifetime pack‐years 0‐10, 10‐20, and 20+, respectively, compared with never smoking (P = .16). In a preplanned exploratory analysis of smoking intensity early in life, the adjusted HR for 12+ pack‐years before age 30 years for DFS was 1.37 (95% CI, 1.02‐1.84) compared with never smoking (P = .04). The adjusted HR for DFS was 1.18 (95% CI, 0.92‐1.50) for past smokers and 1.10 (95% CI, 0.73‐1.64) for current smokers, compared with never smokers.

CONCLUSIONS:

Total tobacco usage early in life may be an important, independent prognostic factor of cancer recurrences and mortality in patients with stage III colon cancer. Cancer 2010. © 2010 American Cancer Society.     

早期乳腺癌放射治疗进展

放射治疗在早期乳腺癌的综合治疗中具有重要地位。在早期浸润性乳腺癌乳房保留治疗已成熟的基础上，近年的临床研究着眼于对乳房保留治疗的标准模式的挑战，包括全乳照射后瘤床加量的意义，是否有低危复发患者可以接受单纯手术以及部分乳腺照射的可行性等。对于局部复发高危患者进行乳房切除术后胸壁和区域淋巴结的放射治疗可以降低2／3的局部和区域的复发率，但是目前仍然只有少数研究证实术后放疗提高了生存率，尤其关于中等复发危险的患者术后放疗是否有价值尚存在较多争议。本文将对上述进展和争议作一综述。     

Conservative surgery followed by radical radiotherapy in the management of stage I carcinoma of the breast

Since October 1976, the treatment policy in our Radiotherapy Center for Stage I carcinoma of the breast has been excision of the tumor mass, when it was cosmetically suitable, followed by irradiation to the breast and periphereal lymphatics. Eighty-three patients were admitted between October 1976 and March 1980. They underwent local excision of the tumor and then received 5000 rad in 5 weeks to the breast, supraclavicular, axillary and internal mammary chain lymph nodes. Each field was treated every day. A boost was then given to the scar, bringing the dose up to 6500 rad, calculated at maximum tumor depth, depending upon the size of the tumor prior to surgery. Cosmetic results were quite good, and the local control rate at 54 months is 98 %. The survival with no evidence of disease (NED) at 54 months (actuarial) is 83 %. There have been 10 failures: 8 distant, 1 local (in axilla, controlled by surgery, actually NED), and 1 local and distant (scar and brain). Both local failures were found within 12 months after treatment, and 8/ 10 of the failures within 24 months. Twenty-one out of 83 patients have had complications (25.3% ); of these, 28.8% were surgical and the remainder resulted from radiotherapy after surgery, either from radiotherapy alone or from combination of treatments. Of the total of 21 complications, 18 were mild and 3 were serious. Of those 3 serious complications (3.6 %), 2 were a result of radiotherapy, and one because an ill-advised axillary dissection prior to radiotherapy gave a negative axilla and a serious arm edema and painful shoulder. This was the worst complication in the total of 83 patients. These results compare favorably with the results achieved in the same Hospital with radical surgery as far as local tumor control and survival with no evidence of disease (NED) is concerned. The results also compare with the great majority of surgical series reported in the literature, allowing us to conclude that patients treated with radiation have nothing to lose and much to gain by preserving the breast.