Complete pathologic response to short-course neoadjuvant alectinib in mediastinal node positive (N2) ALK rearranged lung cancer.

OBJECTIVES: Neoadjuvant therapy prior to surgical resection for locally advanced lung cancer has evolved to incorporate systemic cytotoxic chemotherapy +/- immunotherapy +/- radiotherapy. The role of neoadjuvant precision therapies remains understudied. MATERIALS AND METHODS: We report cases with major and complete pathologic responses to off-label neoadjuvant alectinib. RESULTS: A case with stage IIIA (cT1b cN2 cM0) EML4-ALK variant 3a/b lung adenocarcinoma received 6 weeks of alectinib followed by R0 left upper lobectomy with complete pathological response (ypT0 ypN0). Another case with stage IIIA (cT3 cN2 cM0) EML4-ALK variant 2 received 12 weeks of alectinib followed by R0 right middle lobectomy with a major pathologic response (ypT1a ypN0) but systemic recurrence 12 months post-operatively. CONCLUSION: Ongoing clinical trials are evaluating the role of both neoadjuvant and adjuvant ALK-directed therapy. Our cases support the completion of ongoing trials (ALINA: NCT03456076 and ALNEO: NCT05015010), and highlight the ability of second generation ALK inhibitors to induce major and complete pathologic responses in the neoadjuvant setting plus the likely role of long-term adjuvant kinase inhibitor therapy to prevent radiographic/clinical recurrence.

Patterns of care for non-small-cell lung cancer at an academic institution affiliated with a national cancer institute-designated cancer center.

PURPOSE: Evidence-based treatment guidelines for non-small-cell lung cancer (NSCLC) exist to improve the quality of care for patients with this disease. However, how often evidence-based decisions are used for care of NSCLC is poorly understood. PATIENTS AND METHODS: We examined patterns of care and rate of adherence to evidence-based guidelines for 185 new NSCLC patients seen between 2007 and 2009. Evidence-based care status was determined for 150 patients. RESULTS: Eighty-one percent of the patients were white, the mean age was 66 years, 49% were women, 11% were never smokers, 83% had Eastern Cooperative Oncology Group performance status 0 to 1, 49.7% of tumors were adenocarcinomas, 57.1% of never smokers had tumors genotyped (EGFR, ALK, KRAS), and 13.3% participated in clinical trials. The rate of evidence-based treatment adherence was 94.1% (16 of 17), 100% (21 of 21) and 100% (36 of 36) in patients with stages I, II, and III NSCLC, respectively. Stage IV disease, with adherence of 76.3% (58 of 76), was correlated with a higher rate of nonadherence when compared with stages I-III (odds ratio 16.33; 95% CI, 1.94 to 137.73). In patients with stage IV disease, the rate of evidence-based adherence was 95% (72 of 76) for first-line therapy, 95.2% (40 of 42) for second-line therapy, and only 33.3% (6 of 18) for third-line therapy (P < .001). There was no significant correlation between evidence-based adherence status and the patient's age, sex, performance status, smoking history, ethnicity, or the treating physician. CONCLUSION: These data point toward the need for improved evidence-based use of resources in the third-line setting of stage IV NSCLC.

A prospective study of the psychosocial impact of a positive Chlamydia trachomatis laboratory test.

BACKGROUND: Few data exist on potential harms of chlamydia screening. We assessed the psychosocial impact of receiving a positive Chlamydia trachomatis test result. METHODS: We prospectively studied women ≥16 years of age undergoing chlamydia testing in 2 Midwestern family planning clinics. We surveyed women at baseline and about 1 month after receiving test results, using 9 validated psychosocial scales/subscales and chlamydia-specific questions. Changes in scale scores were calculated for each woman. Mean percent changes in scores for chlamydia-positive and -negative women were compared using a t test. RESULTS: We enrolled 1807 women (response rate, 84%). Of the 1688 women with test results, 149 (8.8%) tested positive. At follow-up, chlamydia-positive women (n = 71) had a 75% increase in anxiety about sexual aspects of their life on the Multidimensional Sexual Self-Concept Questionnaire (P < 0.001), significantly greater than the 26% increase among 280 randomly selected chlamydia-negative women (P = 0.02). There were no differences for the other 8 scales/subscales, including general measures of anxiety, depression, and self-esteem. Chlamydia-positive women were more likely than chlamydia-negative women to be "concerned about chlamydia" (80% vs. 40%, P < 0.001) and to report breaking up with a main partner (33% vs. 11%, P < 0.001) at follow-up. Women testing positive reported a range of chlamydia-specific concerns. CONCLUSIONS: Chlamydia-positive women had significant increases in anxiety about sex and concern about chlamydia, but did not have marked changes in more general measures of psychosocial well-being about 1 month after diagnosis. Chlamydia diagnoses were associated with some disruption of relationships with main partners. Chlamydia-specific concerns may guide counseling messages to minimize psychosocial impact.

Sexually transmitted diseases program performance measures: how are they performing?

BACKGROUND: Performance measures were developed in order to improve the performance of sexually transmitted disease (STD) prevention programs. METHODS: A consultant worked with persons from STD programs and Centers for Disease Control and Prevention to identify possible measures. Measures were pilot tested for feasibility and relevance in several programs, then implemented nationwide in 2004. Data were collated and shared with programs and presented at national meetings. Site visits, webinars, and technical assistance focused on program improvement related to the measures. Reported data were analyzed to see if national performance improved on the activities measured. RESULTS: Some measures were dropped or revised, and quality of reported data improved over time. There was little evidence that overall program performance improved. CONCLUSIONS: Performance measures are one way to monitor performance, and might contribute to program improvement, but additional efforts are needed to improve performance.

Screening and treatment to prevent sequelae in women with Chlamydia trachomatis genital infection: how much do we know?

BACKGROUND: An important question for chlamydia control programs is the extent to which finding and treating prevalent, asymptomatic Chlamydia trachomatis genital infection reduces reproductive sequelae in infected women. METHODS: We reviewed the literature to critically evaluate evidence on the effect of chlamydia screening on development of sequelae in infected women. RESULTS: Two randomized controlled trials of 1-time screening for chlamydial infection-in a Seattle-area health maintenance organization and a Danish school district-revealed that screening was associated with an approximately 50% reduction in the incidence of pelvic inflammatory disease over the following year. However, both of these trials had methodological issues that may have affected the magnitude of observed screening benefits and might limit generalizability to other populations. A large, nonrandomized cohort of chlamydia screening among US Army recruits, although limited by lack of outpatient data, did not find a benefit of similar magnitude to the randomized trials. Methodological limitations restrict valid conclusions about individual benefits of screening using data from historical cohorts and ecological studies. We identified no trials directly evaluating the effect of chlamydia screening on subclinical tubal inflammation or damage, ectopic pregnancy, or tubal factor infertility and no studies addressing the effects of >1 round of screening, the optimal frequency of screening, or the benefits of screening for repeat infections. CONCLUSIONS: Additional studies of the effectiveness of chlamydia screening would be valuable; feasible study designs may depend on the degree to which screening programs are already established. In addition, better natural history data on the timing of tubal inflammation and damage after C. trachomatis infection and development of more accurate, noninvasive tools to assess chlamydial sequelae are essential to informing chlamydia control efforts.

A public health focus on infertility prevention, detection, and management.

In 2002, 2 million American women of reproductive age were infertile. Infertility is also common among men. The Centers for Disease Control and Prevention (CDC) conducts surveillance and research on the causes of infertility, monitors the safety and efficacy of infertility treatment, and sponsors national prevention programs. A CDC-wide working group found that, despite this effort, considerable gaps and opportunities exist in surveillance, research, communication, and program and policy development. We intend to consult with other federal agencies, professional and consumer organizations, the scientific community, the health care community, industry, and other stakeholders, and participate in the development of a national public health plan for the prevention, detection, and management of infertility.

Prevalence of sexually transmitted infections among female adolescents aged 14 to 19 in the United States.

OBJECTIVE: Most young women initiate sexual activity during adolescence; risk for sexually transmitted infections (STIs) accompanies this initiation. In this study we estimated the prevalence of the most common STIs among a representative sample of female adolescents in the United States. METHODS: Data were analyzed from 838 females who were aged 14 to 19 and participating in the nationally representative National Health and Nutrition Examination Survey 2003-2004. After interview and examination, survey participants provided biological specimens for laboratory testing. The main outcome was weighted prevalence of at least 1 of 5 STIs: Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis, herpes simplex virus type 2, and human papillomavirus (HPV) (any of 23 high-risk types or type 6 or 11). RESULTS: Prevalence of any of the 5 STIs was 24.1% among all and 37.7% among sexually experienced female adolescents. HPV (23 high-risk types or type 6 or 11) was the most common STI among all female adolescents (prevalence: 18.3%), followed by C trachomatis infection (prevalence: 3.9%). Prevalence of any of the STIs was 25.6% among those whose age was the same or 1 year greater than their age at sexual initiation and 19.7% among those who reported only 1 lifetime sex partner. CONCLUSIONS: The prevalence of STIs among female adolescents is substantial, and STIs begin to be acquired soon after sexual initiation and with few sex partners. These findings support early and comprehensive sex education, routine HPV vaccination at the age of 11 to 12 years, and C trachomatis screening of sexually active female adolescents.

Dilemmas in the management of syphilis: a survey of infectious diseases experts.

We surveyed infectious diseases consultants to determine how they manage syphilis when there are insufficient data to guide management or when guidelines cannot be followed because of a lack of available definitive diagnostic tests. Most providers did not have access to dark-field microscopy. We found variation in management of syphilis, especially for patients with human immunodeficiency virus infection.

Lung dose-volume parameters and the risk of pneumonitis for patients treated with accelerated partial-breast irradiation using three-dimensional conformal radiotherapy.

PURPOSE: There are no data on how complication rates after accelerated partial-breast irradiation delivered by three-dimensional conformal radiotherapy are affected by treatment technique. We therefore examined the risk of pneumonitis in relation to lung dose-volume parameters. PATIENTS AND METHODS: Our prospective dose-escalation trial enrolled 198 treated patients from 2003 to 2007. Patients received 32 or 36 Gy in 4-Gy fractions, given twice daily: 29 (14%) were treated with pure photons; 149 (77%) with mixed photons and electrons; and 20 (10%) with protons. RESULTS: There were four cases of pneumonitis at 4, 4, 7, and 9 months after treatment. All were in the 36-Gy cohort and were treated with pure photons. The risk of pneumonitis for the two cohorts combined was: 17% (four of 24) for an ipsilateral lung volume (ILV) receiving 20 Gy or higher (ILV, 20 Gy) of 3% or higher (P = .0002 for comparison to ILV 20 Gy < 3%, Fisher's exact test); 20% (four of 20) for an ILV 10 Gy of 10% or higher (P = .0001); and 15% (four of 26) for an ILV 5 Gy of 20% or higher (P = .0002). CONCLUSION: The risk of pneumonitis appeared related to the ILV treated. This volume can be reduced by using mixed photons and electron when possible. We recommend that the ILV 20 Gy should be lower than 3%, the ILV 10 Gy lower than 10%, and the ILV 5 Gy lower than 20% when purely coplanar techniques are used.

Screening male prisoners for Chlamydia trachomatis: impact on test positivity among women from their neighborhoods who were tested in family planning clinics.

BACKGROUND: Chlamydia trachomatis screening test positivity among women in the United States has remained high, leading researchers to suggest that programs should also screen men. Men have been screened in Philadelphia prisons since 2002. Philadelphia prisons are similar to jails in other jurisdictions; in 2003 the median duration of incarceration was 17 days. We studied whether screening and treating men in prison influenced C. trachomatis infection among women living in their communities. METHODS: We divided the city into 2 areas: "high-treatment" (high percentage of men were treated for C. trachomatis detected in prison) and "low-treatment" (low percentage of men were treated for C. trachomatis detected in prison). We compared changes in test positivity among women from those areas, who were tested in family planning clinics during the 2 years before versus the 3 years after the male prison screening program began. RESULTS: In 2002 to 2004, prison screening led to treatment of 1054 infections among 23,203 men aged 20 to 24 years living in high-treatment areas and 98 infections among 21,057 men aged 20 to 24 years in low-treatment areas. Test positivity declined among 20- to 24-year-old women in both areas. In high-treatment areas, positivity decreased 9.1% per year from 1999 to 2001 and 4.9% per year from 2001 to 2004. In low-treatment areas, positivity decreased 13.2% per year from 1999 to 2001 and 7.5% per year from 2001 to 2004. CONCLUSION: C. trachomatis test positivity among 20- to 24-year-old women tested in family planning clinics continued to decrease after men were treated for C. trachomatis; however, we found no evidence that the continued decrease was due to the new prison screening program.

Epidemiology of STD disparities in African American communities.

This article reviews the epidemiology of sexually transmitted disease (STD) disparities for African American communities in the United States. Data are reviewed from a variety of sources such as national case reporting and population-based studies. Data clearly show a disproportionately higher burden of STDs in African American communities compared with white communities. Although disparities exist for both viral and bacterial STDs, disparities are greatest for bacterial STDs such as gonorrhea, chlamydia, and syphilis. Gonorrhea rates among African Americans are highest for adolescents and young adults, and disparities are greatest for adolescent men. Although disparities for men who have sex with men (MSM) are not as great as for heterosexual populations, STD rates for both white and African American MSM populations are high, so efforts to address disparities must also include African American MSM. Individual risk behavior and sociodemographic characteristics of African Americans do not seem to account fully for increased STD rates for African Americans. Population-level determinants such as sexual networks seem to play an important role in STD disparities. An understanding of the epidemiology of STD disparities is critical for identifying appropriate strategies and tailoring strategies for African American communities. Active efforts are needed to reduce not only the physical consequences of STDs, such as infertility, ectopic pregnancy, chronic pelvic pain, newborn disease, and increased risk of HIV infection, but also the social consequences of STDs such as economic burden, shame, and stigma.

Emerging antimicrobial resistance in Neisseria gonorrhoeae: urgent need to strengthen prevention strategies.

Prevention and control of gonorrhea is an important public health concern due to the high burden of disease, the recent increase in reported infection rates, and the reproductive and economic consequences of infection. Effective antibiotic treatment is one essential component of an integrated approach to gonorrhea control. Over the past 60 years, however, development of resistance in Neisseria gonorrhoeae to multiple antimicrobial classes challenges this component of gonorrhea control. An integrated, comprehensive prevention strategy should include enhancement of national and international surveillance systems to monitor antimicrobial resistance and new strategies to maximize the benefit and prolong the utility of antimicrobials, including combination regimens, implementation of screening recommendations for individuals at high risk for infection, and the assurance of prompt and effective treatment for infected persons and their sexual partners. Progress in controlling the epidemic and avoiding a resurgence as treatment options wane will require careful attention to all components of a comprehensive prevention strategy.

Organ deformation and dose coverage in robotic respiratory-tracking radiotherapy.

PURPOSE: Respiratory motion presents a significant challenge in stereotactic body radiosurgery. Respiratory tracking that follows the translational movement of the internal fiducials minimizes the uncertainties in dose delivery. However, the effect of deformation, defined as any changes in the body and organs relative to the center of fiducials, remains unanswered. This study investigated this problem and a possible solution. METHODS AND MATERIALS: Dose delivery using a robotic respiratory-tracking system was studied with clinical data. Each treatment plan was designed with the computed tomography scan in the end-expiration phase. The planned beams were applied to the computed tomography scan in end-inspiration following the shift of the fiducials. The dose coverage was compared with the initial plan, and the uncertainty due to the deformation was estimated. A necessary margin from the clinical target volume to the planning target volume was determined to account for this and other sources of uncertainty. RESULTS: We studied 12 lung and 5 upper abdomen lesions. Our results demonstrated that for lung patients with properly implanted fiducials a 3-mm margin is required to compensate for the deformation and a 5-mm margin is required to compensate for all uncertainties. Our results for the upper abdomen tumors were still preliminary but indicated a similar result, although a larger margin might be required. CONCLUSION: The effect of body deformation was studied. We found that adequate dose coverage for lung tumors can be ensured with proper fiducial placement and a 5-mm planning target volume margin. This approach is more practical and effective than a recent proposal to combine four-dimensional planning with respiratory tracking.

Incidence of neonatal herpes simplex virus infections in two managed care organizations: implications for surveillance.

OBJECTIVES: To estimate the incidence of neonatal herpes simplex virus (HSV) infections and to assess the utility of surveillance methods for neonatal herpes in 2 managed care populations. METHODS: We identified potential cases using 15 discharge International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9) codes for neonatal HSV and other diseases clinically consistent with this diagnosis. We also searched laboratory databases for positive HSV tests and investigated deaths during the neonatal period. We performed medical chart review using a standardized form. Two pediatric infectious disease specialists reviewed the forms of infants who had a positive HSV test or received a herpes-related diagnosis and made a determination as confirmed, probable, or not a case. RESULTS: Among 270,703 infants born from 1997 to 2002, we identified 737 potential cases and completed medical chart abstraction for 699 (95%). Final review identified 35 confirmed or probable cases of neonatal HSV, and the incidence was 12.9 per 100,000 live births. Only 24 (69%) of the 35 cases were confirmed by laboratory testing. Among the 24 confirmed cases, 22 (92%) received an ICD-9 code of 054.xx or 771.2. Among the 60 infants that received an ICD-9 code of 054.xx or 771.2, only 31 (52%) were confirmed or probable cases of neonatal HSV after final review. CONCLUSIONS: About 30% of neonatal HSV cases were not laboratory confirmed. The use of ICD-9 codes of 054.xx and 771.2 was a sensitive but not specific method to identify cases of neonatal herpes.