Preventive health care, 1999 update: 3. Follow-up after breast cancer

OBJECTIVE: To make recommendations to physicians who provide follow-up care for women who have been treated for early-stage breast cancer. OPTIONS: Combination of blood tests, bone scans, liver echography and chest radiography for detection of distant disease; physical examination with or without mammography for detection of contralateral breast cancer; and physical examination with or without mammography for detection of ipsilateral recurrent disease after breast-conserving therapy. OUTCOMES: Survival, disease recurrence and quality-of-life measures for distant disease, local recurrence of disease and disease in the contralateral breast. EVIDENCE: A MEDLINE search for relevant articles published between January 1966 and January 1998 with the MeSH terms "breast neoplasms" and "neoplasm recurrence" (local and distant) with limits to "human" was done. A subsequent MEDLINE search using the MeSH terms "breast neoplasms," "neoplasm recurrence," "local/diagnosis" and "mammography" was done to address issues of mammography. The literature search was reviewed by a medical librarian and 2 breast cancer specialists to ensure completeness. BENEFITS, HARMS AND COSTS: Breast cancer is the most common cancer in Canadian women and is the second leading cause of death after lung cancer. Even with early-stage breast cancer, recurrence after treatment for primary breast cancer is frequent. Traditionally, follow-up has been felt to facilitate early detection and improve survival. Randomized controlled trials (RCTs) have shown that routine screening (blood tests and diagnostic imaging) for distant disease does not alter survival or quality of life over routine physical examination. In an underpowered secondary analysis of RCT data, the detection of contralateral breast cancer did not affect survival. However, there have been no RCTs examining the role of mammography and physical examination and their effect on survival in the detection of contralateral breast cancer. The sensitivity and specificity of mammography after local excision and radiotherapy is unknown. There have been no RCTs examining the role of mammography or physical examination, or both, and their effect on survival in the detection of ipsilateral breast recurrence. VALUES: The strength of evidence was evaluated using the methods of the Canadian Task Force on Preventive Health Care. A high value was placed on interventions that changed survival. When evidence was available, high value was also placed on interventions that affected quality of life. RECOMMENDATIONS: There is good evidence not to include blood work and diagnostic imaging as part of screening for distant disease (grade E recommendation). There is no evidence to suggest that mammography decreases mortality by detecting ipsilateral disease in the conservatively treated breast; however, there is indirect evidence that it may be beneficial (grade C recommendation). There is no direct evidence to suggest that physical examination or mammography, or both, should be used to detect contralateral breast cancer; however, there is indirect evidence that it may be beneficial (grade C recommendation). VALIDATION: The findings of this analysis were reviewed through an iterative process by the members of the Canadian Task Force on Preventive Health Care.     

Hazard-Rate Analysis and Patterns of Recurrence in Early Stage Melanoma: Moving towards a Rationally Designed Surveillance Strategy

Background

While curable at early stages, few treatment options exist for advanced melanoma. Currently, no consensus exists regarding the optimal surveillance strategy for patients after resection. The objectives of this study were to identify patterns of metastatic recurrence, to determine the influence of metastatic site on survival, and to identify high-risk periods for recurrence.

Methods

A retrospective review of the Duke Melanoma Database from 1970 to 2004 was conducted that focused on patients who were initially diagnosed without metastatic disease. The time to first recurrence was computed from the date of diagnosis, and the associated hazard function was examined to determine the peak risk period of recurrence. Metastatic sites were coded by the American Joint Committee on Cancer (AJCC) system including local skin, distant skin and nodes (M1a), lung (M1b), and other distant (M1c).

Results

Of 11,615 patients initially diagnosed without metastatic disease, 4616 (40%) had at least one recurrence. Overall the risk of initial recurrence peaked at 12 months. The risk of initial recurrence at the local skin, distant skin, and nodes peaked at 8 months, and the risk at lung and other distant sites peaked at 24 months. Patients with a cutaneous or nodal recurrence had improved survival compared to other recurrence types.

Conclusions

The risk of developing recurrent melanoma peaked at one year, and the site of first recurrence had a significant impact on survival. Defining the timing and expected patterns of recurrence will be important in creating an optimized surveillance strategy for this patient population.     

Estimation and prediction in a multi-state model for breast cancer

An important aim in clinical studies in oncology is to study how treatment and prognostic factors influence the course of disease of a patient. Typically in these trials, besides overall survival, also other endpoints such as locoregional recurrence or distant metastasis are of interest. Most commonly in these situations, Cox regression models are applied for each of these endpoints separately or to composite endpoints such as disease-free survival. These approaches however fail to give insight into what happens to a patient after a first event. We re-analyzed data of 2795 patients from a breast cancer trial (EORTC 10854) by applying a multi-state model, with local recurrence, distant metastasis, and both local recurrence and distant metastasis as transient states and death as absorbing state. We used an approach where the clock is reset on entry of a new state. The influence of prognostic factors on each of the transition rates is studied, as well as the influence of the time at which intermediate events occur. The estimated transition rates between the states in the model are used to obtain predictions for patients with a given history. Formulas are developed and illustrated for these prediction probabilities for the clock reset approach.     

Adjuvant tamoxifen for operable carcinoma of the breast: report of clinical trial by the Christie Hospital and Holt Radium Institute.

A large controlled clinical trial with the admission of 1005 patients was carried out using tamoxifen as adjuvant treatment for women with operable carcinoma of the breast. Results were analysed for the first 906 evaluable patients randomised up to December 1981. After mastectomy premenopausal women were randomised to receive either an irradiation menopause or tamoxifen 20 mg daily for one year. Postmenopausal women were randomised to receive either tamoxifen 20 mg daily for one year or no systemic treatment (controls). Analysis at five years suggested that for premenopausal women there was no significant difference between an irradiation menopause and tamoxifen in terms of survival, local recurrence, or distant metastases. Tamoxifen had no appreciable side effects. For postmenopausal women there was a trend in favour of tamoxifen with regard to survival and incidence of distant metastases, and the difference became statistically significant for those patients with four or more positive axillary nodes. If long term results of these studies show only an improved quality of remaining life with tamoxifen, then this drug could be an important contribution to adjuvant treatment.     

Haematogenous abdominal wall metastasis of differentiated, alpha-fetoprotein-negative hepatocellular carcinoma after previous antiandrogen therapy within a site of lipoma manifestation since childhood

Background

The guidelines established by the National Comprehensive Cancer Network do not describe mucinous histology as a clinical factor that should influence the therapeutic algorithm. However, previous studies show conflicting results regarding the prognosis of colorectal mucinous adenocarcinoma. In this study, we described the clinicopathological features of mucinous adenocarcinoma in Japan, to identify optimal therapeutic strategies.

Methods

144 patients with mucinous and 2673 with non-mucinous adenocarcinomas who underwent primary resection in two major centers in Yokohama, Japan were retrospectively evaluated for clinicopathological features and treatment factors. A multivariate analysis for overall survival followed by the comparison of overall survival using Cox proportional hazard model were performed.

Results

Patients with mucinous adenocarcinoma had larger primary lesions, higher preoperative CEA levels, a deeper depth of invasion, higher rates of nodal and distant metastasis, and more metastatic sites. A multivariate analysis for overall survival revealed a mucinous histology to be an independent prognostic factor. In the subgroup analysis stratified by stage, Patients diagnosed as StageIII and IV disease had a worse survival in mucinous adenocarcinoma than non-mucinous, while survival did not differ significantly in patients diagnosed as Stage0-II disease. In StageIII, local recurrence in rectal cases and peritoneal dissemination were more frequently observed in patients with a mucinous histology.

Conclusions

Our study indentified that mucinous adenocarcinoma was associated with a worse survival compared with non-mucinous in patients with StageIII and IV disease. In rectal StageIII disease with mucinous histology, additional therapy to control local recurrence followed by surgical resection may be a strategical alternative. Further molecular investigations considering genetic features of mucinous histology will lead to drug development and better management of peritoneal metastasis     

Recurrence patterns of pancreatic cancer treated with adjuvant intensity modulated radiotherapy

BackgroundThe aim of this study was to investigate the recurrence patterns in pancreatic cancer patients treated with adjuvant intensity modulated radiotherapy (IMRT) and to correlate the sites of locoregional recurrence with radiotherapy target volumes.Materials and methodsThirty-eight patients who had undergone resection and adjuvant chemoradiation for pancreatic cancer were evaluated. Radiotherapy (RT) was started after 1–3 cycles of adjuvant chemotherapy (CHT). Clinical target volume (CTV) was contoured according to the RTOG guideline. All patients were treated with IMRT with a dose of 45–50.4 Gy. Computerized tomography (CT) images at the time of recurrence were correlated with radiotherapy plans. Locoregional recurrences were classified as in-field, out-field and marginal.ResultsMedian overall survival (OS) was 19 months. One- and 2-year OS rates were 73.6% and 37.1%, respectively. Locoregional recurrence and distant metastases were observed in 11 (28.9%) and 23 (60.5%) patients, respectively. For the 11 locoregional recurrences, 7 were in-field, 1 was marginal, and 3 were out-of-field. One patient had isolated local, 2 patients had isolated regional and 15 (57.6%) patients had only distant failures. The first presentations of failures were mostly distant (58%). On multivariate analysis, tumor size ≥ 3 cm (p = 0.011) and positive vascular invasion (p = 0.014) predicted for worse OS rate.ConclusionsThe majority of locoregional recurrences were in the radiation field among pancreatic cancer patients treated with postoperative IMRT. However, failures were predominantly distant, and improvement of systemic control may be of particular interest.     

Serum proteomic pattern for predicting recurrence of undifferentiated nasopharyngeal carcinoma after radiotherapy

Although most patients with early-stage nasopharyngeal carcinoma (NPC) can be cured by radiotherapy, there is a high recurrence rate in patients with advanced NPC. We attempted to identify proteomic patterns in sera for predicting tumor recurrence. Pretreatment sera were collected from 64 NPC patients with complete remission after radiotherapy. Serum proteins were profiled by SELDI ProteinChip technology, and correlated with local/distant recurrence. Forty proteomic features were significantly different between the patient groups with and without tumor recurrence. Univariate analyses showed that 32 of them were significantly associated with time to first recurrence. Multivariate Cox-regression analyses identified International Union Against Cancer (UICC) stage and two proteomic features with mass/charge (m/z) values of 8808 and 6626 as independent prognostic indicators for tumor recurrence. The hazard ratios were 2.0 (95% confidence interval, CI 1.3–3.2) and 0.79 (95% CI 0.64–0.96) for a double of peak intensity of proteomic feature m/z 8808 and m/z 6626, respectively. These two proteomic features were also independent prognosticators for overall survival. A decision tree was constructed to predict the tumor recurrence by using UICC stage, proteomic feature m/z 8808, and proteomic feature m/z 6626, and evaluated by Leave-One-Out crossvalidation. Kaplan-Meier analysis confirmed that the decision tree could predict both recurrencefree survival and overall survival. The positive and negative predictive values for tumor recurrence within 4 yr were 74 and 89%, respectively. A serum proteomic pattern comprising features m/z 8808 and m/z 6626 is a potential surrogate marker of disease recurrence after radiotherapy in NPC.     

Evaluation of adjuvant chemotherapy in patients with colorectal cancer in Primorsko-Goranska and Istarska County--a twenty years retrospective study

Colorectal cancer is the second most common malignant disease in developed countries, with about one million new cases worldwide every year, accompanied with high mortality rate. We examined the survival rate and recurrence (occurrence of distant metastases and/or local recurrence) of patients with colorectal cancer in Primorsko-Goranska and Istarska County who received adjuvant chemotherapy, compared to those who did not in the period since 1980. until 1999. This study involves 483 patients with colorectal cancer stages II and III of Primorsko-Goranska and Istarska County, which were underwent curative resections of colorectal cancer at the Clinical Hospital Centre Rijeka, and then treated with chemotherapy (288) or without Chemotherapy (195). We analyzed the five year survival rate and the recurrence of malignant disease in the adjuvant treatment group in comparison with not treated group with chemotherapy, depending on the stage of disease, degree of histological differentiation, patient age and location of cancer (colon or rectum). After follow-up of 60 months died 44.79% (129/288) of patients who received chemotherapy and 53.33% (104/195) of patients who did not receive chemotherapy. The relative risk of death (from any cause) in chemotherapy-treated group versus the group without chemotherapy was 0.82 (p < 0.008). Recurrence of malignant disease in the chemotherapy group was 38.54% (111/288), and in the group without chemotherapy was 46.15% (90/195). The relative risk of recurrence of malignant disease in the chemotherapy group versus the group without chemotherapy was 0.78 (p < 0.001). There was no difference in treatment efficacy regard to the localization of the tumor, but there were differences in efficiency with respect to disease stage, grade and age. Chemotherapy with 5-fluorouracil and leukovorin ameliorate the survival and reduces recurrence and distant metastases in patients with colorectal cancer stages II and III.     

紫杉醇脂质体联合顺铂同步放疗对老年宫颈癌有较好疗效

本研究将178例具有危险因素的老年宫颈癌术后患者随机分为研究组和对照组各89例,对照组给予紫杉醇联合顺铂同步放化疗方案,研究组给予紫杉醇脂质体联合顺铂同步放化疗方案,观察2组患者治疗期间的毒副反应及1年、2年、3年生存率、局部复发率和远处转移率,以期探讨老年宫颈癌患者术后不同化疗方案联合同步放疗的有效性和安全性。研究结果表明:研究组骨髓抑制、消化道反应、肝肾功能异常、脱发发生率低于对照组(p<0.05);研究组1年、2年、3年生存率与对照组相比较均无统计学差异(p>0.05);研究组与对照组1年、2年、3年局部复发率和远处转移率相比较差异均无统计学意义(p>0.05)。本研究初步结论认为,老年宫颈癌患者术后采用紫杉醇脂质体联合顺铂同步放化疗方案更为安全有效,采用紫杉醇脂质体代替紫杉醇注射液值得在临床推广应用。     

Treatment of Early Breast Cancer: A Report after Ten Years of a Clinical Trial

A controlled clinical trial has been carried out to compare radical mastectomy with wide excision (extended tylectomy) in the treatment of early breast cancer. Only patients aged 50 and over were included and 370 entered the trial during a period of 10 years. Postoperative radiotherapy was given in each case. In patients with clinically involved axillary nodes there was a significantly higher incidence of local and distant recurrence in those having a wide excision, and the survival of these patients was significantly less than those who had a radical mastectomy. In patients with clinically uninvolved nodes, although there was a significantly higher incidence of local recurrence in those having a wide excision, there was no increased incidence of distant recurrence and the survival rate was similar to those having a radical mastectomy.     

Postoperative Serum Levels of sCD26 for Surveillance in Colorectal Cancer Patients

One of the main aims of the follow-up after curative resection of colorectal cancer is the early detection and treatment of tumor recurrence. We previously demonstrated decreased preoperative soluble CD26 (sCD26) levels in serum from colorectal cancer patients. We extended now the study to investigate if sCD26 levels in postoperative serum serve as marker of recurrence of the disease during surveillance. Soluble sCD26 was measured in pre- and postoperative serum samples of 43 patients with primary colorectal cancer. Carcinoembryonic antigen, carbohydrate antigen 19.9 and 72.4 levels were also measured during surveillance. The average follow-up period was 41.8±20.8 months. sCD26 levels during follow-up showed well-defined patterns in patients without disease (n = 28), and in patients with tumor persistence (n = 2), local recurrence (n = 3) or distant metastasis (n = 10). Disease-free patients showed stable levels between 460–850 ng/mL during follow-up, while high (over 850 ng/mL) and unstable sCD26 levels were found before recurrence was diagnosed. The mean maximum/minimum sCD26 ratios during surveillance were 1.52, 2.12 and 2.63 for patients with no recurrence, local recurrence and metastasis, respectively (p = 0.005). From the cut-off obtained from a receiver operator characteristics (ROC) curve built with the maximum/minimum sCD26 ratios and the upper and lower cut-offs of sCD26, we were able to discriminate patients with and without recurrent disease. We propose that the measurement of serum sCD26 during the follow-up of patients diagnosed of colorectal cancer could be valuable for the early detection of local and distant recurrence. A large, randomized, prospective trial should be performed to confirm our findings.     

Monitoring response, prediction methodology, staging, and imaging in prostate cancer

The predictive values of various tests and examinations are assessed as they relate to prostate cancer progression and treatment. The usefulness of post-treatment biopsy specimens is greatest 2 years after radiation therapy completion. Gleason grading is not reliable in the setting of hormonal ablation therapy. For patients with extracapsular extension, the survival curves separate depending on whether positive or negative surgical margins are obtained. Prostate-specific antigen doubling time is increasingly used as an indicator of disease recurrence after local therapy and prostate cancer-specific survival.     

The role of oral acyclovir in the management of genital herpes simplex.

Oral acyclovir is an antiviral nucleoside analogue that has recently been released in Canada for use in selected patients with genital infections by the herpes simplex virus. First episodes of genital herpes should be treated with oral acyclovir as soon as the diagnosis is considered. Most people with recurrent genital herpes do not require systemic drug therapy. Selected patients with severe or long-lasting recurrences, recurrences associated with long prodromal periods (greater than 12 to 24 hours) or systemic complications such as erythema multiforme and eczema herpeticum may receive measurable benefit from treatment at the onset of symptoms. In most patients frequently recurrent disease can be suppressed with long-term therapy. Since long-term safety beyond 1 year has not been established, suppressive therapy should be stopped at least once per year to reassess the recurrence pattern. Acyclovir has not been adequately tested for safety in pregnancy and should not be prescribed for pregnant women unless the potential benefits outweigh the risks. Careful attention to disease severity, accurate diagnosis and exclusion of other causes of genital lesions will ensure that the drug is used only when beneficial.     

Breast cancer recurrence after immediate reconstruction: patterns and significance

Local recurrence of cancer after mastectomy and immediate breast reconstruction is generally regarded as a poor prognostic indicator. This study was conducted to identify specific patterns of local recurrence following reconstruction and to determine their biological significance. The records of all patients who had undergone immediate breast reconstruction at The University of Texas M. D. Anderson Cancer Center between June 1, 1988, and December 31, 1998, were reviewed. The records of patients who had local tumor recurrence were then carefully analyzed. During this 10-year period, a local recurrence of cancer was found to have developed in 39 of 1694 patients (2.3 percent). Most recurrences were in the skin or subcutaneous tissue (n = 28; 72 percent), and the remainder were in the "chest wall" (n = 11; 28 percent), as defined by skeletal or muscular involvement. Transverse rectus abdominis myocutaneous flaps were used most often in both groups, but latissimus dorsi myocutaneous flaps and implant techniques were also used in some patients. Patients with subcutaneous tissue recurrence had an overall survival rate of 61 percent at follow-up of 80.8 months, compared with patients with chest wall recurrence, whose survival rate was 45 percent at similar follow-up. Metastases were less likely to develop in patients with subcutaneous tissue recurrence than in those with chest wall recurrence (57 percent versus 91 percent; p = 0.044); the former group also had a greater chance of remaining disease-free after treatment of the recurrence (39 percent versus 9 percent), respectively. Metastasis-free survival was higher in patients with subcutaneous tissue recurrence than with chest wall recurrence (2-year and 5-year survival: 52 and 42 percent versus 24 and 24 percent; p = 0.04). In both groups, the time to detection of the recurrence was similar (subcutaneous tissue recurrence, 27.1 months, versus chest wall recurrence, 29.5 months). Distant disease did not develop in one patient only in the chest wall recurrence group; this patient remained disease-free at 70 months. From these results, it was concluded that (1) not all local recurrences are the same: patients with subcutaneous tissue recurrence have better survival rates, a decreased incidence of metastases, and a greater chance of remaining disease-free than do those with chest wall recurrence; (2) immediate breast reconstruction (although potentially, it can conceal chest wall recurrence) does not seem to delay the detection of chest wall recurrence; and (3) even if a chest wall recurrence develops, it is highly associated with metastatic disease, and the survival rate is not likely to have been influenced by earlier detection. These data support the continued use of immediate breast reconstruction without fear of concealing a recurrence or influencing the oncologic outcome.     

Copy number alterations and allelic ratio in relation to recurrence of rectal cancer

Background

In rectal cancer, total mesorectal excision surgery combined with preoperative (chemo)radiotherapy reduces local recurrence rates but does not improve overall patient survival, a result that may be due to the harmful side effects and/or co-morbidity of preoperative treatment. New biomarkers are needed to facilitate identification of rectal cancer patients at high risk for local recurrent disease. This would allow for preoperative (chemo)radiotherapy to be restricted to high-risk patients, thereby reducing overtreatment and allowing personalized treatment protocols. We analyzed genome-wide DNA copy number (CN) and allelic alterations in 112 tumors from preoperatively untreated rectal cancer patients. Sixty-six patients with local and/or distant recurrent disease were compared to matched controls without recurrence. Results were validated in a second cohort of tumors from 95 matched rectal cancer patients. Additionally, we performed a meta-analysis that included 42 studies reporting on CN alterations in colorectal cancer and compared results to our own data.

Results

The genomic profiles in our study were comparable to other rectal cancer studies. Results of the meta-analysis supported the hypothesis that colon cancer and rectal cancer may be distinct disease entities. In our discovery patient study cohort, allelic retention of chromosome 7 was significantly associated with local recurrent disease. Data from the validation cohort were supportive, albeit not statistically significant, of this finding.

Conclusions

We showed that retention of heterozygosity on chromosome 7 may be associated with local recurrence in rectal cancer. Further research is warranted to elucidate the mechanisms and effect of retention of chromosome 7 on the development of local recurrent disease in rectal cancer.

Electronic supplementary material

The online version of this article (doi:10.1186/s12864-015-1550-0) contains supplementary material, which is available to authorized users.     

Prognostic factors for recurrence and survival in axillary node-negative breast cancer

The question of which node-negative breast cancer patients should be treated with adjuvant systemic therapy is a debatable topic. Our approach in San Antonio is to examine the risk profile for an individual patient and attempt to classify the patient into a good risk group or a high risk group in terms of disease recurrence. Features such as small tumor size (less than 2 cm), diploid tumors with low proliferative rate, and nuclear grade I, all indicate a good prognosis with a disease-free survival of approx. 90% at 5 yr. Examination of the cost vs benefits in this category of patients suggest that routine treatment with systemic adjuvant therapy is not appropriate.     

Prognostic significance of plasminogen activator inhibitor-1 in breast cancer, with special emphasis on locoregional recurrence-free survival

The independent prognostic value of protease uPA and its inhibitor PAI-1 for survival in breast cancer patients is firmly established. However, there is very little data on the prognostic value of serine proteases and their inhibitors for locoregional recurrence in breast cancer. The prognostic value of PAI-1 for local control in a group of 766 patients treated at our institute with either breast conserving treatment or modified radical mastectomy was evaluated. The locoregional recurrence-free survival (LRFS) of patients with PAI-1 values above the median value was significantly worse than that of patients with PAI-1 values below the median value (log-rank; p=0.0078). In multivariate analysis PAI-1 levels proved to be of independent statistical significance for LRFS (p=0.0401, relative risk 2.28, 95% confidence interval 1.04-5.02). The independent prognostic value of PAI-1 for metastasis-free survival and overall survival was also confirmed. In addition, our data suggest that PAI-1 antigen levels in tumor tissue might be of prognostic value for survival after locoregional recurrence (log-rank; p=0.0618). According to our findings, PAI-1 levels could be used as a biological marker that could facilitate the identifation of patients with a higher risk of local relapse already at the time of primary treatment. These patients should then be offered more aggressive treatment.     

Survival after intratumoral interleukin-2 treatment of 72 melanoma patients and response upon the first chemotherapy during follow-up

Systemic high-dose interleukin-2 (IL-2) treatment achieves long-term survival in a subset of advanced patients with melanoma. As we reported previously, intratumoral IL-2 induced complete local responses in more than 60% of melanoma patients. This study aimed to analyze the long-term outcome of 72 patients treated in two prior trials. Melanoma patients (49 stage III, 23 stage IV) with injectable metastases received intratumoral IL-2 injections thrice weekly at individually escalated doses (median duration, 6.5 weeks; median total IL-2 dose, 72 MIU; median number of injected metastases, 10). The observed 2-year overall survival rates were 95.5% for stage III patients with cutaneous metastases only (stage IIIB), 72% for those with combined cutaneous and lymph node involvement (stage IIIC), 66.7% for stage IV patients with disease limited to distant soft-tissue metastases (stage IV M1a), and 9.1% for those with visceral metastases (stage IV M1b and stage IV M1c). Thirty patients who reported recurrence of unresectable distant metastases subsequently received chemotherapy in the further course of disease and showed an overall response rate of 36.7% (16.7% complete responses, 20% partial responses). A high total dose of IL-2 and a dacarbazine/temozolomide-based chemotherapy regimen were variables correlated with a clinical response. In conclusion, patients with cutaneous metastasis without lymph node involvement in stage III and with soft-tissue metastasis without visceral involvement in stage IV showed unexpected favorable survival rates after intratumoral treatment with IL-2. Furthermore, the intratumoral IL-2 treatment seemed to be associated with increased complete and partial responses in subsequent chemotherapies.     

Radiofrequency ablation as locoregional therapy for unresectable hepatic malignancies: initial results in 24 patients with 5-years follow-up

Radiofrequency ablation (RFA) is one treatment modality for unresectable liver metastases. Patients with hepatic malignancies (n = 24) underwent elective RFA. All tumors were ablated with a curative intent, with a margin of 1 cm, in a single session of RFA. The median diameter of tumor was 3.1 cm (range 1.7-6.9 cm). Studied patients were not candidates for resection due to multifocal hepatic disease, extrahepatic disease, proximity to major vascular structures or presence of cirrhosis with functional hepatic reserve inadequate to tolerate major hepatic resection. Complete tumor necrosis was achieved in 87.5% and tumor recurred in 3 patients (12.5%) with lesions larger than 5 cm. Distant intrahepatic recurrence was diagnosed in another 4 (16.7%). Distant metastases were found in 7 (29.2%) patients. Four of these 7 patients had also distant intrahepatic recurrence of disease. Two and 5-years survival rates were 41.7% (10 patients) and 8.3% (2 patients) respectively. RFA is safe and effective option for patients with unresectable hepatic malignancies smaller than 5 cm without distant metastatic disease. RF ablation resulted in complete tumor necrosis in 87.5% with 2 and 5-years survival rates much higher than with chemotherapy alone or only supportive therapy, when survival is measured in weeks or months. If RFA is unavailable, percutaneous ethanol injection therapy can be done but with inferior survival rates.     

Using SCC Antigen and CRP Levels as Prognostic Biomarkers in Recurrent Oral Cavity Squamous Cell Carcinoma

Squamous cell carcinoma antigen (SCC-Ag) and C-reactive protein (CRP) levels have been successfully used to stratify risk groups in primary oral squamous cell carcinoma (OSCC) patients; however, related biomarkers have rarely been investigated in recurrent OSCC. The purpose of the present study was to analyze the relationships of SCC-Ag and CRP levels at the time of recurrence with clinical factors and prognosis. We retrospectively recruited patients with recurrence in a cohort of 534 OSCC patients between March 2001 and July 2013. One hundred patients had recurrence. The serum SCC-Ag and CRP levels were measured at the time of cancer diagnosis, 3 to 6 months after treatment with clinical disease-free, and at the time of recurrence. The SCC-Ag levels were significantly lowered after treatment (paired t-test: p = 0.001) and re-elevated at the time of recurrence (paired t-test: p = 0.027). An SCC-Ag level ≥2.0 ng/ml and a CRP level ≥5.0 mg/L at the time of recurrence were significantly associated with recurrent tumor status (P<0.001), recurrent nodal metastasis (χ² trend test: P = 0.020), distant metastasis (P<0.001), and overall survival (P<0.001). Moreover, the influence of both elevated SCC-Ag and CRP levels on overall survival (P<0.001, H.R. [95% CI]: 5.406 [2.210–13.222]) still existed after adjusting for the recurrent tumor stage and patient age. The present study demonstrates that concurrent high levels of both SCC-Ag and CRP at the diagnosis of recurrence acts as a predictor of recurrent tumor status, recurrent advanced tumor stage, distant metastasis, and survival after the diagnosis of recurrence. This study expands the applicability of these two markers in the risk stratification in recurrent OSCC.