Uncontrolled cell proliferation is the hallmark of cancer, and tumor cells have typically acquired damage to genes that directly regulate their cell cycles. Genetic alterations affecting p16(INK4a) and cyclin D1, proteins that govern phosphorylation of the retinoblastoma protein (RB) and control exit from the G1 phase of the cell cycle, are so frequent in human cancers that inactivation of this pathway may well be necessary for tumor development. Like the tumor suppressor protein p53, components of this "RB pathway," although not essential for the cell cycle per se, may participate in checkpoint functions that regulate homeostatic tissue renewal throughout life.

http://science.sciencemag.org/content/sci/274/5293/1672.full.pdf

Cancer Cell Cycles

Objective. —To identify and quantify the major external (nongenetic) factors that contribute to death in the United States. Data Sources. —Articles published between 1977 and 1993 were identified through MEDLINE searches, reference citations, and expert consultation. Government reports and compilations of vital statistics and surveillance data were also obtained. Study Selection. —Sources selected were those that were often cited and those that indicated a quantitative assessment of the relative contributions of various factors to mortality and morbidity. Data Extraction. —Data used were those for which specific methodological assumptions were stated. A table quantifying the contributions of leading factors was constructed using actual counts, generally accepted estimates, and calculated estimates that were developed by summing various individual estimates and correcting to avoid double counting. For the factors of greatest complexity and uncertainty (diet and activity patterns and toxic agents), a conservative approach was taken by choosing the lower boundaries of the various estimates. Data Synthesis. —The most prominent contributors to mortality in the United States in 1990 were tobacco (an estimated 400000 deaths), diet and activity patterns (300 000), alcohol (100 000), microbial agents (90 000), toxic agents (60 000), firearms (35 000), sexual behavior (30 000), motor vehicles (25 000), and illicit use of drugs (20 000). Socioeconomic status and access to medical care are also important contributors, but difficult to quantify independent of the other factors cited. Because the studies reviewed used different approaches to derive estimates, the stated numbers should be viewed as first approximations. Conclusions. —Approximately half of all deaths that occurred in 1990 could be attributed to the factors identified. Although no attempt was made to further quantify the impact of these factors on morbidity and quality of life, the public health burden they impose is considerable and offers guidance for shaping health policy priorities. (JAMA. 1993;270:2207-2212)

https://jamanetwork.com/journals/JAMA/articlepdf/409171/jama_270_18_038.pdf

Actual causes of death in the United States.

Endostatin: an endogenous inhibitor of angiogenesis and tumor growth.

NOTE The report of the Committee without its annexes appears as Official Records of the General Assembly, Sixty-third Session, Supplement No. 46. The designations employed and the presentation of material in this publication do not imply the expression of any opinion whatsoever on the part of the Secretariat of the United Nations concerning the legal status of any country, territory, city or area, or of its authorities, or concerning the delimitation of its frontiers or boundaries. The country names used in this document are, in most cases, those that were in use at the time the data were collected or the text prepared. In other cases, however, the names have been updated, where this was possible and appropriate, to reflect political changes. Scientific Annexes Annex A. Medical radiation exposures Annex B. Exposures of the public and workers from various sources of radiation INTROdUCTION 1. In the course of the research and development for and the application of atomic energy and nuclear technologies, a number of radiation accidents have occurred. Some of these accidents have resulted in significant health effects and occasionally in fatal outcomes. The application of technologies that make use of radiation is increasingly widespread around the world. Millions of people have occupations related to the use of radiation, and hundreds of millions of individuals benefit from these uses. Facilities using intense radiation sources for energy production and for purposes such as radiotherapy, sterilization of products, preservation of foodstuffs and gamma radiography require special care in the design and operation of equipment to avoid radiation injury to workers or to the public. Experience has shown that such technology is generally used safely, but on occasion controls have been circumvented and serious radiation accidents have ensued. 2. Reviews of radiation exposures from accidents have been presented in previous UNSCEAR reports. The last report containing an exclusive chapter on exposures from accidents was the UNSCEAR 1993 Report [U6]. 3. This annex is aimed at providing a sound basis for conclusions regarding the number of significant radiation accidents that have occurred, the corresponding levels of radiation exposures and numbers of deaths and injuries, and the general trends for various practices. Its conclusions are to be seen in the context of the Committee's overall evaluations of the levels and effects of exposure to ionizing radiation. 4. The Committee's evaluations of public, occupational and medical diagnostic exposures are mostly concerned with chronic exposures of …

sources and effects of ionizing radiation

Background Cetuximab is effective in platinum-resistant recurrent or metastatic squamous-cell carcinoma of the head and neck. We investigated the efficacy of cetuximab plus platinum-based chemotherapy as first-line treatment in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck. Methods We randomly assigned 220 of 442 eligible patients with untreated recurrent or metastatic squamous-cell carcinoma of the head and neck to receive cisplatin (at a dose of 100 mg per square meter of body-surface area on day 1) or carboplatin (at an area under the curve of 5 mg per milliliter per minute, as a 1-hour intravenous infusion on day 1) plus fluorouracil (at a dose of 1000 mg per square meter per day for 4 days) every 3 weeks for a maximum of 6 cycles and 222 patients to receive the same chemotherapy plus cetuximab (at a dose of 400 mg per square meter initially, as a 2-hour intravenous infusion, then 250 mg per square meter, as a 1-hour intravenous infusion per week) for a maximum of 6 cycles. Patients with stable disease who received chemotherapy plus cetuximab continued to receive cetuximab until disease progression or unacceptable toxic effects, whichever occurred first. Results

/pdf/platinum-based-chemotherapy-plus-cetuximab-in-head-and-neck-2c129qnqh9.pdf

Platinum-Based Chemotherapy plus Cetuximab in Head and Neck Cancer

BACKGROUND

Although the benefits of mammography are established in women age ≥ 50 years, its use in women age < 50 years is controversial. It is the purpose of this study to determine whether the better outcome in mammographically detected breast carcinoma compared with clinically detected breast carcinoma observed in women age ≥ 50 years also is observed in women age < 50 years.



METHODS

The authors analyzed 869 cases of Stage I and II breast carcinoma in women treated with breast-conserving therapy between 1984-1994. The median follow-up was 43 months (range, 3-128 months). Three hundred and eighteen patients (37%) presented with mammographic abnormalities without clinical signs of disease and 551 patients (63%) presented with clinical signs of disease. The median age of the patients was 56 years (range, 22-88 years). Three hundred and four patients (35%) were age < 50 years.



RESULTS

Mammographically detected tumors in women age < 50 years were of similar size to those in women age ≥ 50 years (median 1.1 cm vs. 1.0 cm). Axillary lymph node involvement and tumor grade were not significantly different between these two groups. However, in women age < 50 years the clinically detected tumors were found to be significantly larger, more likely to be axillary lymph node positive, and of higher grade compared with tumors in older women. Consequently, in patients with mammographically detected tumors, there was no significant difference in recurrence free survival (RFS) between women age < 50 years compared with women age ≥ 50 years (90% and 92%, respectively; P = 0.4), whereas in patients with clinically detected tumors there was a significant difference in 5-year RFS (77% vs. 87%, respectively; P = 0.02).



CONCLUSIONS

Mammography results in the diagnosis of smaller and lower grade breast carcinoma. If mammographically detected, there appears to be no difference in RFS between women age < 50 years and those women age ≥ 50 but there is a difference if the tumors are clinically detected. If left to grow to the size necessary for clinical detectability, the disease appears to be more aggressive in younger women. Cancer 1998;82:2221-2226. © 1998 American Cancer Society.

The benefits of mammography are not limited to women of ages older than 50 years.

We have recently updated the follow-up of 644 women with pathologically determined Stage I (T1N0M0) (474 patients) and Stage II (T1N1M0) (170 patients) breast carcinoma treated by modified or radical mastectomy from 1964 through 1970 at Memorial Sloan-Kettering Cancer Center. Median follow-up was 18.2 years with over 90% of surviving patients followed for 15.7 years. Recurrences occurred in 166 (26%) with 148 (23%) dead of disease and 18 (3%) alive with recurrence when last seen. A nonmammary malignant neoplasm (NMMN) was confirmed in 86 (13%) of the 644 patients. Of these, 55/86 (64%) were diagnosed after and 27 (32%) were diagnosed before the breast carcinoma. Four patients (5%) had a NMMN before and after the breast carcinoma. The most frequent sites of prior carcinoma were the cervix (n = 8), colon-rectum (n = 7), and oropharynx (n = 5), whereas the more common locations of subsequent NMMN were the ovary (n = 11), colon-rectum (n = 10), lung (n = 9), stomach (n = 6), and lymphoma-leukemia (n = 5). There was not a statistically significant difference in the frequency of subsequent NMMN when patients who received adjuvant radiation were compared with those who received adjuvant thiotepa or no adjuvant therapy. There was no excess of lymphoma or of other NMMN in the treated region or of contralateral breast carcinoma among adjuvant radiation treated patients. The overall hazard rate for subsequent NMMN was 7/1.000 women at risk per year. The risk was fairly stable over the first 15 years of follow-up but rose to 12/1,000 in the 15-20-year period. The observed frequency and time distribution of NMMN were very similar to the expected frequency determined by comparison with a population of age-matched women. Most fatal NMMN arose in the ovaries, stomach, women. Most fatal NMMN arose in the ovaries, stomach, pancreas, and lungs. There were 35 deaths due to NMMN detected subsequent to the diagnosis of breast carcinoma (15% of all cancer deaths and 64% of 55 subsequent NMMN). In this series, subsequent NMMN were as frequent as contralateral breast carcinoma, and they were responsible for seven times more deaths. Hence, an important goal of any follow-up program for breast cancer patients should be the early detection and treatment of NMMN.

Nonmammary malignant neoplasms in patients with stage I (T1N0M0) and stage II (T1N1M0) breast carcinoma. A long-term follow-up study.

The prevailing view is that a physician can simultaneously husband economic resources to control health care costs and fulfill a doctor's traditional responsibility to put the patient first. I disagree.

The patient and the public good.

PURPOSE Patients with localized prostate cancer and their doctors face complex trade-offs when deciding on treatment. In this study, we modify the "number needed to treat" method to compare radical prostatectomy with radiotherapy. METHODS A MEDLINE search was performed to identify all studies of radical protatectomy or radiotherapy for prostate cancer. Number needed to treat formulas were modified to account for not only survival but also for complications and their utilities. RESULTS The unadjusted number needed to treat value for overall survival was 6 favoring prostatectomy (six patients have to undergo prostatectomy to have one more 10-year survivor than if they had undergone radiotherapy). Radiotherapy patients were 4 years older than prostatectomy patients. Because overall survival is strongly linked to patients' age and overall health, the numbers needed to treat for disease-specific and distant metastasis-free survival were analyzed to minimize patient selection bias. The unadjusted number needed to treat values for disease-specific and distant metastasis-free survival were 14 and 18, respectively. When number needed to treat is adjusted for complications and utilities, its value for overall survival is 14, disease-specific survival is -25, and distant metastasis free survival is -22, these last two favoring radiotherapy. CONCLUSIONS Utility-adjusted numbers needed to treat for prostatectomy and radiotherapy are greatly influenced by the likelihood of complications and the utility loss ascribed to them. When literature-reported values are used, radiotherapy is superior, but the differences in outcomes are small. With prostate-specific antigen screening and refined treatment methods, these values will change, and the modified number needed to treat can be used to evaluate, report and compare results. The consequences of treatment in terms of both survival and quality of life determine patient choice and physician recommendations.

An evidence-based analysis of the management of localized prostate cancer.

One hundred sixteen patients with stage III carcinoma of the breast were treated by primary radiation therapy. The 5-year actuarial survival and relapsefree survival were 25% and 22%, respectively. The 5-year actuarial probability of local tumor control for the entire group was 64%. In patients undergoing an excisional biopsy and an interstitial implant of the primary tumor area, local control was 100%. In patients who had either an excisional biopsy or an implant, the 5-year actuarial probability of local control was 77% and 76%, respectively. In contrast, in patients having neither an excisional biopsy nor an implant, local control was only 41%. In patients receiving a total dose of greater than 6000 rad, from external beam treatment or from external beam plus an interstitial implant, the local control was 78% compared to 39% in patients receiving a total dose of less than 6000 rad. Forty-one patients received some form of adjuvant therapy. Both local control and relapse-free survival were improved in patients receiving chemotherapy as the sole adjuvant and in patients receiving chemotherapy combined with an endocrine ablative procedure. However, patients treated with only an endocrine ablative procedure had no improvement in survival nor in local control. These results indicate that primary radiation therapy can provide local control in a high proportion of patients with stage III carcinoma of the breast and suggest that chemotherapy is effective in improving both local control and survival in these patients. Cancer 43:985–993, 1979.

Samuel Hellman

Papers

The benefits of mammography are not limited to women of ages older than 50 years.

Nonmammary malignant neoplasms in patients with stage I (T1N0M0) and stage II (T1N1M0) breast carcinoma. A long-term follow-up study.

The patient and the public good.

An evidence-based analysis of the management of localized prostate cancer.

Results of treating stage III carcinoma of the breast by primary radiation therapy