Posttraumatic stress-related psychological functioning in adult survivors of childhood cancer

Purpose

The majority of research examining posttraumatic stress symptoms/disorder (PTSS/PTSD) among adult survivors of childhood cancer has been oriented to cancer, assuming that cancer has been the most traumatic experience in their lives. Whether that assumption is valid, and how it might impact assessment of PTSS, is unknown.

Methods

Survivors in the St. Jude Lifetime Cohort study completed an assessment of PTSS without cancer orientation, global psychological functioning, perceived stress, and cancer-related anxiety.

Results

Participants (n = 2969; M_age = 32.5 ± 8.5 years, 24.1 years since diagnosis, 49.1% female) obtained a mean score on the PTSD Checklist of 27.7, which is comparable to a normative population. Using established cutoffs, 11.8% obtained scores in the at-risk range. Multivariable modeling indicated that psychological factors [global distress (p < 0.0001), perceived stress (p = 0.001), cancer-related anxiety (p < 0.0001)] and demographic variables [female gender (p < 0.0001), survivors with less than a college education (p = 0.002)] were risk factors for increased PTSS. Only 14.5% identified a cancer-related traumatic event, and there was no difference in PTSS scores between those who identified cancer vs. non-cancer events as most stressful (28.4 ± 12.6 vs. 28.5 ± 12.7, p = 0.93).

Conclusion

One in eight adult long-term survivors of childhood cancer had PTSS above the cutoff, though subgroups (e.g., females and those with lower education) report more distress symptoms. Most adult survivors do not identify cancer as their most stressful event.

Implications for cancer survivors

Screening for distress in survivorship clinics should not assume that distress is directly related to the survivor’s cancer experience.

     

Prognostic significance of cell proliferation in human neuroblastoma: comparison with other prognostic factors

Peripheral neuroblastic tumors (PNT), are heterogeneous neoplasms that include neuroblastoma (NB), ganglioneuroblastoma (GNB) and ganglioneuroma (GN) and present great biological heterogeneity. There are few reports analyzing PCNA and Ki-67 expression in PNT; however, controversy exists concerning the specificity of PCNA as a real proliferative marker. The objective of our study was to determine which of these cellular proliferation markers is more specific on cellular cycle and could contribute with more information on the cell cycle. We found that PCNA was expressed in NB unfavourable cases, with MYCN amplification and high mitosis-karyorrhexis-index (MKI). Whereas, Ki-67 showed statistical significance regarding cases unfavourable with intermediate and high MKI, aneuploid and stages 3 and 4. Survival showed that patients with tumor not expressing Ki-67 (MIB1) lived longer than those without PCNA (88.93 vs 74.05%). We conclude that Ki-67 expression permits reliable detection of the cellular proliferation neuroblastoma fraction and provides useful prognostic information when associated with other biological factors.     

Time to death in breast cancer patients as an indicator of treatment response

Purpose

Determine the efficacy and safety of first-line ribociclib plus letrozole in elderly patients with HR+, HER2? advanced breast cancer.

Methods

668 postmenopausal women with HR+, HER2? advanced breast cancer and no prior systemic therapy for advanced disease were enrolled in the Phase III MONALEESA-2 trial (NCT01958021); 295 patients were aged ≥ 65 years. Patients were randomized to ribociclib (600 mg/day; 3-weeks-on/1-week-off) plus letrozole (2.5 mg/day) or placebo plus letrozole until disease progression, unacceptable toxicity, death, or treatment discontinuation. The primary endpoint was PFS, which was evaluated in elderly (≥ 65 years) and younger (< 65 years) patients. Secondary endpoints included response rates and safety.

Results

Ribociclib plus letrozole significantly improved PFS vs placebo plus letrozole in elderly (hazard ratio: 0.608; 95% CI 0.394–0.937) and younger patients (hazard ratio: 0.523; 95% CI 0.378–0.723). Overall response rates were numerically higher in the ribociclib vs placebo arm, regardless of age. Ribociclib plus letrozole was well tolerated in elderly patients, with the safety profile similar to the overall study population. Nausea, vomiting, alopecia, and diarrhea were > 10% more frequent in the ribociclib plus letrozole vs placebo plus letrozole arm in both subgroups; most events were grade 1/2. In elderly patients, grade 1/2 anemia and fatigue were > 10% more frequent in the ribociclib plus letrozole vs placebo plus letrozole arm and discontinuation rates were similar in both arms.

Conclusions

Addition of ribociclib to letrozole is a valid therapeutic option for elderly patients with HR+, HER2? advanced breast cancer in the first-line setting.

     

Tonsil T cell immunity to human papillomavirus in the absence of detectable virus in healthy adults

BACKGROUND: Human papillomavirus (HPV) is known to infect the epithelium of the upper aerodigestive tract; however, major questions regarding prevalence and persistence of infection, and their relation to local immune response, remain unanswered. OBJECTIVES: To evaluate the tonsil T cell immune response to HPV and compare this to the frequency of detectable virus at this site. STUDY DESIGN: A cross-sectional study of cancer-free adults undergoing routine tonsillectomy. METHODS: Mucosal immune responses to recombinant HPV16 L2E6E7 and HPV6 L2E7 antigens were measured by tonsillar T-lymphocyte proliferation assay in 13 subjects. HPV deoxyribonucleic acid (DNA) was assessed by PCR and reverse line-blot hybridization in an expanded population of 44 subjects. RESULTS: Proliferative T-cell responses to HPV16 and HPV6 were identified in all patients. The presence of a CD45RO+ T cell population responsive to HPV6 L2E7 was confirmed in three of six subjects tested. There were no CD45RO+ responses to HPV16 L2E6E7 and no evidence of current or latent HPV infection of the tonsil. CONCLUSIONS: T cell memory to human papillomavirus can be identified in tonsil tissue from an adult population in the absence of concurrent HPV infection. How novel HPV vaccines might augment this preexisting cell-mediated immunity is an essential area for investigation.     

Radioquimioterapia complementaria a cirugía radical en el adenocarcinoma de recto

A retrospective analysis of the results with radio-chemotherapy in rectal carcinoma B2-3 and C is presented. A total of 120 patients received postoperative treatment with chemotherapy (5-fluorouracil plus folinic acid) 6 courses, 2 courses concurrent with radiotherapy. The acute and chronic toxicity, local and distance control, disease free survival (DFS) and overall survival (OS) were evaluated. With a mean follow up of 23 months, the actuarial OS and DFS at 4 years were 83% and 72%, with 20 relapses (6 locoregional and 14 distant failure). Acute intestinal toxicity (degree III–IV), 28%; haematological, 18,3%. 16% of the patients presented chronic toxicity, bowel obstruction in six cases. Significant difference was found in the relapse rate, related to the onset of chemoradiotherapy, 2nd course versus 3rd course: 12% versus 29% (p=0.1) but without decrease overall survival. This scheme of postoperative radiochemotherapy in the rectal carcinoma produces a high local control, DFS and OS.     

Genetic and biochemical studies in Argentinean patients with variegate porphyria

Background  

A partial deficiency in Protoporphyrinogen oxidase (PPOX) produces the mixed disorder Variegate Porphyria (VP), the second acute porphyria more frequent in Argentina. Identification of patients with an overt VP is absolutely important because treatment depends on an accurate diagnosis but more critical is the identification of asymptomatic relatives to avoid acute attacks which may progress to death.