Age-related differences in breast cancer treatment

Background: More than half of the cases of breast cancer treated in the United States occur in women over age 65. This study investigates age-related differences in breast cancer therapy. Methods: A retrospective review of all women with primary operable invasive breast cancer treated at the University of Michigan Breast Care Center over a 30-month period showed a total of 77 older patients aged 65 years (median, 71; oldest patient, 92) for whom full information was available regarding comorbidity, tumor stage and histology, and details of surgery, radiation, and chemohormonal therapy and complications. Fifty-one similar younger patients aged 55–64 years (median, 59) were identified for comparison. Patients were classified as either having received standard treatment or nonstandard treatment. Standard therapy was prospectively defined as follows: local/regional—lumpectomy and axillary lymph node dissection plus radiation therapy or modified radical mastectomy; systemic—chemotherapy and/or tamoxifen for stage II disease. A comorbidity score calculated for each patient assigned one point each for nursing home residence, nonambulatory status, recent surgery, and each medical problem requiring drug therapy. Results: When overall treatment (local/regional plus systemic) was assessed, proportionately fewer older patients (55 of 77 versus 47 of 51;p<0.01) received standard treatment. Fewer older than younger patients (62 of 77 versus 50 of 51;p<0.01) received surgical therapy that included an axillary dissection. A smaller proportion of older patients received radiation therapy following lumpectomy and axillary lymph node dissection (26 of 29 versus 19 of 19; N.S.). Overall, only 59 of 77 older patients versus 50 of 51 younger patients (p<0.001) received standard local/regional care. Similar proportions of younger and older patients (19 of 22 and 24 of 30, respectively) received standard systemic therapy for stage II breast cancer, but older patients were less likely to receive chemotherapy than younger patients (7% versus 50%;p<0.001). Treatment-related complications were not age-related but were more frequent in patients receiving standard treatment than in patients receiving nonstandard treatment (45 of 102 versus two of 26;p<0.001). Comorbidity score correlated with the use of nonstandard therapy but not with age. The scores for both older and younger patients receiving overall standard treatment were 0.8 versus 1.5 and 1.4, respectively, in patients receiving nonstandard treatment. Interestingly, explanations for decisions to deviate from standard treatment guidelines were often not identified. Comorbidity was explicitly noted in only one of four younger patients who received nonstandard treatment therapy. In 22 older patients who received nonstandard treatment, comorbidity was cited in eight cases, patient age was cited in six cases, and patient choice was cited in four cases. Follow-up (median, 34 months) did not show that disease-free or overall survival differences were related to age or to treatment (standard versus nonstandard). Conclusions: These data demonstrate age-related variations in breast cancer treatment in a multidisciplinary breast care unit. Lower complication rates and equivalent short-term outcomes in women who received nonstandard therapy suggest good clinical judgment may have played a role in these differences. Although age-related patient preferences and comorbidity are relevant, the age-related attitudes of caregivers must also be taken into account to fully explain these variations.Presented at the 46th Annual Cancer Symposium of the Society of Surgical Oncology, Los Angeles, March 18–21, 1993.     

RENAL TRANSPLANTATION – AN EARLY EXPERIENCE

Renal transplant (RT) is now a therapy of choice for end stage renal disease (ESRD). The Nephrology Unit, Asvini started functioning in Dec 90 and to date 1298 sittings of hemodialysis have been given to 45 patients. Of these, 35 were in ESRD and 11 patients underwent renal transplantation at this hospital during the period Jan 91 – Dec 93. One patient expired after 18 months of transplantation due to infection. Early experience in screening patients for RT, use of immunosuppression, management of rejection episodes and protocol are presented with special emphasis on its relevance to the Armed Forces.KEY WORDS: Transplantation, Renal Failure, Immunosuppression, Rejection     

Evaluation of merbarone (NSC 336628) in disseminated malignant melanoma

Merbarone, NSC 336628, is an investigational anticancer drug with activity against experimental animal tumors including melanoma. This paper presents results of a Phase II clinical study of merbarone in patients with biopsy proven stage IV malignant melanoma without prior chemotherapy and with no evidence of CNS involvement. Thirty-five patients with median age 58 (range 27–81), with performance status 0–2 were treated with merbarone 1000 mg/m²/day for five days by intravenous continuous infusion repeated every 3 weeks. All patients (21 males and 14 females) were evaluable for toxicity. Two patients were not evaluable for response having been removed from protocol treatment due to toxicity and received other treatment during the first course of chemotherapy. Among the evaluable patients there was one complete response in a supraclavicular lymph node lasting four months and one partial liver response lasting three months. The remaining thirty-one patients were non-reponders. Of these one had a stable disease lasting 21 months. The overall objective response rate was 6% (2/35) with a 95% confidence interval of 1%–19%. Twenty-six of the 35 patients have died. The estimated median survival of the entire group was 9 months with a 95% confidence interval of six to eleven months. Renal toxicity was dose-limiting and manifested as increasing serum creatinine (54% of patients), proteinuria (51%) and hematuria (9%). One patient experienced grade 4 creatinine increase, proteinuria and acute renal failure. Other toxicities included nausea (71%), vomiting (51%), malaise (23%), weakness (20%), alopecia (17%), diarrhea (17%), anorexia (14%), transaminase (SGOT, SGPT) increase (14%), constipation (14%), alkaline phosphatase or 5nucleotidase increase (9%), and fever (9%). Hematologictoxicity (granulocytopenia, leukopenia, and anemia) was generally mild and infrequent (29%, only one patient had grade 4 granulocytopenia). Overall 9 patients (26%) had at least one grade 3 toxicity. We conclude that merbarone at this dose and schedule has detectable but minimal activity in the treatment of metastatic malignant melanoma and given the significant renal toxicity this schedule does not merit further evaluation in this disease.     

HIV AND TUBERCULOSIS CO-INFECTION IN A REFERRAL CHEST HOSPITAL

Serving personnel of Armed Forces admitted with tuberculosis between Apr 1996–1999 were evaluated for co-infection of tuberculosis and HIV. Sixty (1.06%) of tuberculosis patients were found to be HIV positive. Initial test was done by spot kits and subsequently confirmed by ELISA on two different samples. Majority of the cases were in sexually active age group 48 (80%). Alcohol and smoking was associated in 80% cases. Thirty six (60%) were sputum smear positive for AFB. Twenty eight (46.7%) gave history of exposure to sex workers. Family members were not available for study. Sero prevalence of HIV in association with tuberculosis is less in Armed Forces compared to civil population.KEY WORDS: HIV, Seroprevalence, Tuberculosis     

Muramyl dipeptide: Not just another brick in the wall

The robust expression of microbial pattern recognition receptors such as TLR4 and Nod2 in intestinal stem cells reflects an active communication dynamic between the host and the gut microbiota. A new study reveals that muramyl dipeptide, the bacterial cell wall peptidoglycan motif, activates Nod2 within crypt base columnar Lgr5-positive stem cells and promotes their survival. Apart from the immediate relevance to the growth of organoids for in vitro experiments, the study raises new questions about the molecular mechanisms whereby gut microbes influence intestinal physiology.     

Combined Analysis of Phase III Trials Evaluating [99mTc]Tilmanocept and Vital Blue Dye for Identification of Sentinel Lymph Nodes in Clinically Node-Negative Cutaneous Melanoma

Background

[^99mTc]Tilmanocept is a CD206 receptor-targeted radiopharmaceutical designed for sentinel lymph node (SLN) identification. Two nearly identical nonrandomized phase III trials compared [^99mTc]tilmanocept to vital blue dye.

Methods

Patients received [^99mTc]tilmanocept and blue dye. SLNs identified intraoperatively as radioactive and/or blue were excised and histologically examined. The primary end point, concordance, was the proportion of blue nodes detected by [^99mTc]tilmanocept; 90 % concordance was the prespecified minimum concordance level. Reverse concordance, the proportion of radioactive nodes detected by blue dye, was also calculated. The prospective statistical plan combined the data from both trials.

Results

Fifteen centers contributed 154 melanoma patients who were injected with both agents and were intraoperatively evaluated. Intraoperatively, 232 of 235 blue nodes were detected by [^99mTc]tilmanocept, for 98.7 % concordance (p < 0.001). [^99mTc]Tilmanocept detected 364 nodes, for 63.7 % reverse concordance (232 of 364 nodes). [^99mTc]Tilmanocept detected at least one node in more patients (n = 150) than blue dye (n = 138, p = 0.002). In 135 of 138 patients with at least one blue node, all blue nodes were radioactive. Melanoma was identified in the SLNs of 22.1 % of patients; all 45 melanoma-positive SLNs were detected by [^99mTc]tilmanocept, whereas blue dye detected only 36 (80 %) of 45 (p = 0.004). No positive SLNs were detected exclusively by blue dye. Four of 34 node-positive patients were identified only by [^99mTc]tilmanocept, so 4 (2.6 %) of 154 patients were correctly staged only by [^99mTc]tilmanocept. No serious adverse events were attributed to [^99mTc]tilmanocept.

Conclusions

[^99mTc]Tilmanocept met the prespecified concordance primary end point, identifying 98.7 % of blue nodes. It identified more SLNs in more patients, and identified more melanoma-containing nodes than blue dye.     

A Collision of Diseases: Chronic Lymphocytic Leukemia Discovered During Lymph Node Biopsy for Melanoma

Background

In the United States in 2012, there were 16,060 new cases of chronic lymphocytic leukemia (CLL). Often CLL is clinically occult and first detected during pathologic evaluation of the sentinel lymph node biopsy (SLNB). We reviewed our experience of patients with the coexisting diagnosis of melanoma and CLL.

Methods

An institutional review board-approved review was performed on patients with CLL and melanoma treated from 1995 to 2009 at Moffitt Cancer Center and compared with the incidence of melanoma and CLL in our tumor registry patients with breast, prostate, lung, and colon cancer.

Results

Fifty-two patients (44 males; median age, 71 years [range, 46–88]) were identified with concurrent diagnoses of melanoma and CLL. Twenty-two patients (42 %) had CLL on SLNB for their melanoma. Thirty-two patients (62 %) were diagnosed with melanoma before CLL. Concomitant or prior cancer diagnoses included nonmelanoma skin cancers (N = 29), prostate (N = 6), colorectal (N = 2), and Merkel cell carcinoma (N = 2). Five of 20 patients (25 %) had metastatic melanoma found at the time of SLNB. Patients with melanoma had a tenfold increase of CLL diagnosis compared with colorectal cancer patients, an eightfold increase compared to prostate cancer patients, and a fourfold increase compared with breast cancer patients.

Conclusions

We have confirmed an increased association of CLL and melanoma. This may be related to an underlying immunologic defect; however, there has been scant investigation into this phenomenon. Surgeons and pathologists should understand this occurrence and recognize that not all grossly enlarged or abnormal sentinel lymph nodes in melanoma patients represent melanoma.