Outcome of neoadjuvant treatment for pancreatic cancer in elderly patients: comparative, observational cohort study.

BACKGROUND: Use of neoadjuvant therapy for elderly patients with pancreatic cancer has been debatable. With FOLFIRINOX (folinic acid, 5-fluorouracil, irinotecan, oxaliplatin) or gemcitabine plus nab-paclitaxel (GnP) showing tremendous effects in improving the overall survival of patients with borderline resectable and locally advanced pancreatic cancer, there is no definitive consensus regarding the use of this regimen in the elderly. METHODS: This study evaluated the eligibility of elderly patients with borderline resectable or locally advanced pancreatic cancer for neoadjuvant therapy. Patients registered in the database of pancreatic cancer at the University of Colorado Cancer Center, who underwent neoadjuvant treatment between January 2011 and March 2019, were separated into three age groups (less than 70, 70-74, 75 or more years) and respective treatment outcomes were compared. RESULTS: The study included 246 patients with pancreatic cancer who underwent neoadjuvant treatment, of whom 154 and 71 received chemotherapy with FOLFIRINOX and GnP respectively. Among these 225 patients, 155 were younger than 70 years, 36 were aged 70-74 years, and 34 were aged 75 years or older. Patients under 70 years old received FOLFIRINOX most frequently (124 of 155 versus 18 of 36 aged 70-74 years, and 12 of 34 aged 75 years or more; P < 0.001). Resectability was similar among the three groups (60.0, 58.3, and 55.9 per cent respectively; P = 0.919). Trends towards shorter survival were observed in the elderly (median overall survival time 23.6, 18.0, and 17.6 months for patients aged less than 70, 70-74, and 75 or more years respectively; P = 0.090). After adjusting for co-variables, age was not a significant predictive factor. CONCLUSION: The safety and efficacy of multiagent chemotherapy in patients aged 75 years or over were similar to those in younger patients. Modern multiagent regimens could be a safe and viable treatment option for clinically fit patients aged at least 75 years.

Conceptualising SEL in the Cross-Cultural Spaces of Primary Schools in Aotearoa New Zealand.

Social and emotional learning (SEL) to support students' wellbeing is even more critical within schools dealing with the COVID-19 pandemic. This article establishes why New Zealand primary schools need strategies to support the emotional wellbeing of students and why a prescriptive approach is not appropriate for the bicultural and multicultural classroom context. It draws on Maori, Indigenous, Pasifika, international psychology and decolonialisation views to propose directions for future research in this vital area of education. Seeing SEL from different world views highlights the opportunity and ethical necessity for cultural, social and emotional learning (CSEL) to create transformative spaces that support holistic wellbeing.

Total neoadjuvant therapy for rectal cancer.

While outcomes for patients with locally advanced disease have improved considerably with combined modality therapy, there is now an emphasis on developing risk-adapted treatment strategies. Moreover, the primary cause of death from locally advanced rectal cancer is related to distant progression, which now exceeds the rate of local failure. Thus, the necessity to optimally address micrometastatic disease has led to increasing interest in delivering chemotherapy in the neoadjuvant setting rather than in the postoperative setting. This review critically appraises the emerging literature on the options for sequencing of therapy, focusing on the total neoadjuvant therapy paradigm as well as emerging options for omitting components of multimodality therapy.

Outcomes of induction chemotherapy followed by chemoradiation using intensity-modulated radiation therapy for esophageal adenocarcinoma.

This study looks at toxicity and survival data when chemoradiation (CRT) is delivered using intensity-modulated radiation therapy (IMRT) after induction chemotherapy. Forty-one patients with esophageal adenocarcinoma treated with IMRT from March 2007 to May 2009 at Memorial Sloan-Kettering Cancer Center were analyzed. All patients received induction chemotherapy prior to CRT. Thirty-nine percent (n = 16) of patients underwent surgical resection less than 4 months after completing CRT. Patients were predominantly male (78%), with a median age of 68 years (range 32-85 years). The majority of acute treatment-related toxicity was hematologic or gastrointestinal, with 17% of patients having grade 3+ hematologic toxicity and 12% of patients having grade 3+ gastrointestinal toxicity. Only two patients developed grade 2-3 pneumonitis (5%) and 5 patients experienced post-operative pulmonary complications (29%). Eight patients (20%) required a treatment break. With a median follow up of 41 months for surviving patients, 2-year overall survival was 61%, and the cumulative incidences of local failure (LF) and distant metastases were 40% and 51%, respectively. This rate of LF was reduced to 13% in patients who underwent surgical resection. Surgery and younger age were significant predictors of decreased time to LF on univariate analysis. Induction chemotherapy followed by CRT using IMRT in the treatment of esophageal cancer is well tolerated and is not associated with an elevated risk of postoperative pulmonary complications. The use of IMRT may allow for integration of more intensified systemic therapy or radiation dose escalation for esophageal adenocarcinoma, ultimately improving outcomes for patients with this aggressive disease.

Acute effects of pelvic irradiation on the adult uterus revealed by dynamic contrast-enhanced MRI.

OBJECTIVE: Pelvic radiation therapy (RT) can influence fertility in female rectal cancer survivors. Data regarding its effects on the adult uterus are scant. This study aims to evaluate the uterus before and after RT, using dynamic contrast-enhanced MRI. METHODS: Eligible patients (n=10) received RT for rectal cancer, had an intact uterus and underwent dynamic contrast-enhanced MRI before and after RT. Seven patients were pre-menopausal. RESULTS: Patients received pelvic RT (median, 50.2 Gy) with concurrent 5-fluorouracil. Five patients were treated with intensity modulated RT (IMRT) and five with a three-field technique. The median D95 of the uterus was 30 Gy; D05 was 48 Gy; and V95 was 97%. The median cervical D95 was 45 Gy; D05, 50 Gy; and V95, 100%. Cervical dose was higher with IMRT than with three-field plans (p≤0.038). On T2 MRI, the junctional zone was visible in nine patients before and in one after RT (p=0.001). Median cervical length (2.3 vs 3.0 cm) and endometrial thickness (2.6 vs 5.9 mm) were reduced after RT (p≤0.008). In pre-menopausal patients, the volume transfer constant, K(trans), (0.069 vs 0.195, p=0.006) and the extracellular extravascular volume fraction, V(e), (0.217 vs 0.520, p=0.053) decreased. CONCLUSION: Pelvic RT significantly affected uterine anatomy and perfusion. Cervical dose was higher with IMRT than three-field plans, but no attempt was made to constrain the dose. ADVANCES IN KNOWLEDGE: Pelvic RT significantly affects the adult uterus. These findings are crucial to understand the potential consequences of RT on fertility, and they lay the groundwork for further prospective studies.

Evaluation of deformable image registration and a motion model in CT images with limited features.

Deformable image registration (DIR) is increasingly used in radiotherapy applications and provides the basis for a previously described model of patient-specific respiratory motion. We examine the accuracy of a DIR algorithm and a motion model with respiration-correlated CT (RCCT) images of software phantom with known displacement fields, physical deformable abdominal phantom with implanted fiducials in the liver and small liver structures in patient images. The motion model is derived from a principal component analysis that relates volumetric deformations with the motion of the diaphragm or fiducials in the RCCT. Patient data analysis compares DIR with rigid registration as ground truth: the mean ± standard deviation 3D discrepancy of liver structure centroid positions is 2.0 ± 2.2 mm. DIR discrepancy in the software phantom is 3.8 ± 2.0 mm in lung and 3.7 ± 1.8 mm in abdomen; discrepancies near the chest wall are larger than indicated by image feature matching. Marker's 3D discrepancy in the physical phantom is 3.6 ± 2.8 mm. The results indicate that visible features in the images are important for guiding the DIR algorithm. Motion model accuracy is comparable to DIR, indicating that two principal components are sufficient to describe DIR-derived deformation in these datasets.

Recurrence and survival after pathologic complete response to preoperative therapy followed by surgery for gastric or gastrooesophageal adenocarcinoma.

BACKGROUND: To characterise recurrence patterns and survival following pathologic complete response (pCR) in patients who received preoperative therapy for localised gastric or gastrooesophageal junction (GEJ) adenocarcinoma. METHODS: A retrospective review of a prospective database identified patients with pCR after preoperative chemotherapy for gastric or preoperative chemoradiation for GEJ (Siewert II/III) adenocarcinoma. Recurrence patterns, overall survival, recurrence-free survival, and disease-specific survival were analysed. RESULTS: From 1985 to 2009, 714 patients received preoperative therapy for localised gastric/GEJ adenocarcinoma, and 609 (85%) underwent a subsequent R0 resection. There were 60 patients (8.4%) with a pCR. Median follow-up was 46 months. Recurrence at 5 years was significantly lower for pCR vs non-pCR patients (27% and 51%, respectively, P=0.01). The probability of recurrence for patients with pCR was similar to non-pCR patients with pathologic stage I or II disease. Although the overall pattern of local/regional (LR) vs distant recurrence was comparable (43% LR vs 57% distant) between pCR and non-pCR groups, there was a significantly higher incidence of central nervous system (CNS) first recurrences in pCR patients (36 vs 4%, P=0.01). CONCLUSION: Patients with gastric or GEJ adenocarcinoma who achieve a pCR following preoperative therapy still have a significant risk of recurrence and cancer-specific death following resection. One third of the recurrences in the pCR group were symptomatic CNS recurrences. Increased awareness of the risk of CNS metastases and selective brain imaging in patients who achieve a pCR following preoperative therapy for gastric/GEJ adenocarcinoma is warranted.

Multimodality treatment with intensity modulated radiation therapy for esophageal cancer.

The objective of this study is to determine the feasibility and report the outcome of patients with locally advanced esophageal cancer treated with preoperative or definitive chemoradiotherapy (CRT) using intensity-modulated radiation therapy (IMRT). Between 2003 and 2007, 30 patients with non-cervical esophageal cancer received concurrent chemotherapy and IMRT at Stanford University. Eighteen patients were planned for definitive CRT and 12 were planned for preoperative CRT. All patients had computed tomography-based treatment planning and received IMRT. The median dose delivered was 50.4 Gy. Patients planned for preoperative CRT underwent surgery 4-13 weeks (median 8.3 weeks) following completion of CRT. Median follow-up of surviving patients from start of RT was 24.2 months (range 8.2-38.3 months). The majority of tumors were adenocarcinomas (67%) and poorly differentiated (57%). Tumor location was 7% upper, 20% mid, 47% lower, and 27% gastroesophageal junction. Actuarial 2-year local-regional control (LRC) was 64%. High tumor grade was an adverse prognostic factor for LRC and overall survival (OS) (P= 0.015 and 0.012, respectively). The 2-year LRC was 83% vs. 51% for patients treated preoperatively vs. definitively (P= 0.32). The 2-year disease-free and OS were 38% and 56%, respectively. Twelve patients (40%) required feeding tube placement, and the average weight loss from baseline was 4.8%. Twelve (40%) patients experienced grade 3+ acute complications and one patient died of complications following feeding tube placement. Three patients (10%) required a treatment break. Eight patients (27%) experienced grade 3 late complications. No grade 4 complications were seen. IMRT was effective and well tolerated. Disease recurrence remains a challenge and further investigation with dose escalation to improve LRC and OS is warranted.

Tissue effects after stereotactic body radiotherapy using cyberknife for patients with abdominal malignancies.

AIMS: To report the tissue effects of treatment with single fraction stereotactic body radiotherapy (SBRT) using Cyberknife on malignant tumours of the abdomen and adjacent normal organs. MATERIALS AND METHODS: The data from four autopsies with unresectable pancreatic carcinoma and one lymph node excision from a case of recurrent neuroblastoma were reviewed for radiation-related tissue effects within the primary cancer and the normal organs within the radiation field. RESULTS: Cases of unresectable pancreatic carcinoma consistently showed radiation-induced changes in both the primary tumour and the adjacent, non-malignant colorectal tissue. An additional case of lymph nodes exposed to stereotactic radiation showed typical radiation-related changes, including lymphocyte depletion and capsular fibrosis. CONCLUSIONS: A myriad of radiation-related tissue effects are seen after SBRT with Cyberknife. The changes parallel those reported after conventionally fractionated radiotherapy and suggest that the pathophysiological mechanisms of radiation-induced normal tissue damage are similar for biologically equivalent single and fractionated doses of radiotherapy.

Preoperative versus postoperative radiotherapy for locally advanced gastroesophageal junction and proximal gastric cancers: a comparison of normal tissue radiation doses.

Locoregional relapse occurs in over half of gastric cancer patients who undergo potentially curative resection. Adjuvant chemoradiation reduces locoregional relapse, but often requires irradiating large fields and is limited by poor patient tolerance. This study explores the potential dosimetric benefit in reducing the radiation dose to normal structures by treating gastroesophageal (GE) junction/proximal gastric cancers with preoperative rather than adjuvant radiotherapy. Five cases of GE junction/proximal gastric cancer patients treated postoperatively with curative intent were selected. The actual target contours were then modified to reflect hypothetical target volumes which would have been used had the patients been treated preoperatively. Hypothetical preoperative treatment plans were generated for each patient based on these modified contours. The hypothetical preoperative treatment plans were then compared to the actual postoperative plans with respect to dose-volume parameters including lung mean dose, lung V20, heart V20 and V30, and mean doses to abdominal structures. Target volumes were smaller with preoperative treatment, with an average reduction of 23%. Comparative dose-volume histogram (DVH) analysis showed the resultant composite lung doses were reduced in the preoperative plans by 50-79%. In all patients, the proportion of lungs receiving at least 20 Gy (V20) was substantially reduced using preoperative treatment (1.9% vs. 9.7% in the 3-D conformal patient; mean of 3.1% vs. 17.6% in the intensity modulated radiation therapy patients). Likewise, the volume of heart receiving at least 30 Gy was dramatically reduced in all preoperative plans (15.8% vs. 35.4%). Doses to the kidneys, liver and spinal cord were comparable in both approaches. Preoperative treatment of GE junction and proximal gastric cancer patients offers the potential to decrease the radiation dose received by normal thoracic structures.

Relationship between pattern of enhancement and local control of brain metastases after radiosurgery.

PURPOSE: A desired goal in the radiosurgery (RS) of brain metastases is improved local control. Our earlier retrospective review identified pattern of enhancement on day-of-treatment imaging as a prognostic indicator for freedom from progression (FFP) after RS in 219 brain metastases. The current study was performed to corroborate this preliminary finding. METHODS AND MATERIALS: Records and imaging studies of patients treated with RS from 1991 to 1997 were reviewed. Each metastasis was categorized as homogeneously-, heterogeneously-, or ring-enhancing. Kaplan-Meier FFP was calculated from the date of RS to the first imaging showing tumor progression. Univariate and multivariate analyses were performed using Cox proportional hazard models stratified by primary site and type of RS (alone, as a boost, or for recurrence). RESULTS: Of 682 lesions in 258 patients, 518 lesions in 193 patients were evaluable. Pattern of enhancement was homogeneous in 59%, heterogeneous in 32%, and ring-like in 8% of lesions. One-year FFP probabilities for homogeneously-, heterogeneously-, and ring-enhancing lesions were 90% (95% confidence interval, 84-93%), 76% (64-84%), and 57% (35-74%), respectively. The p-value for pattern of enhancement from the stratified multivariate analysis was 0.019 adjusting for RS dose and treatment period (1991-1994 vs. 1995-1997). Similar results were achieved adjusting for tumor volume instead of RS dose. CONCLUSION: Pattern of enhancement is confirmed as a significant prognostic factor for FFP of brain metastases treated with RS, independent of dose and volume. A possible explanation is radioresistance of hypoxic tumor cells associated with necrotic regions, suggesting future investigations with radiosensitizers, hypoxic cell sensitizers, or strategies to improve tumor oxygenation.

Case-control study of seropositivity for cysticercosis in Cuenca, Ecuador.

The prevalence of neurocysticercosis has been well documented in rural communities in Latin America using the enzyme-linked inmmunoelectrotransfer blot (EITB) assay. We studied the prevalence of neurocysticercosis in an urban, upper-middle class population in Cuenca, Ecuador. Family members of 34 index cases with parenchymal neurocysticercosis on a computed tomography (CT) scan and family members of 14 patients who had normal CT scans after a trauma or migraine were enrolled in the study. Serum was obtained from 226 individuals, 173 (72%) from the case families and 67 (28%) from the control families. Twelve percent of the case family members and 4% of the control family members were seropositive by the EITB assay. This was a statistically significant difference (P < 0.05) when age and education were held constant by logistic regression. Seropositivity was not related to age. No neurologic symptom proved predictive of serostatus and the only demographic variable that correlated with seropositivity was increased crowding. Positive serology in index cases did correlate with CT findings as follows: 86% of patients with active lesions, 67% with transitional lesions, and only 41% of patients with inactive lesions were positive by the EITB assay. Eighteen percent of family members with a positive EITB test result had parenchymal lesions on a subsequent CT scan. This study demonstrates a high rate of seropositivity of cysticercosis among urban, middle to upper-middle class individuals in a region endemic for Taenia solium. Household contacts of patients with neurocysticercosis had a three-fold higher risk of positive serology for cysticercosis, in comparison with controls.

Compliance with recommended follow-up after percutaneous breast core biopsy.

OBJECTIVE: The purpose of this study was to use information from an established patient tracking system to evaluate patient outcome and assess patient compliance with recommended follow-up after percutaneous breast core biopsy. MATERIALS AND METHODS: All breast core biopsies performed from January 1994 through February 14, 1996, that used stereotaxic or sonographic guidance were reviewed. Clinical, imaging, and pathologic findings were correlated with patient outcomes established by recommended surgical and nonsurgical follow-up. RESULTS: Of 160 core biopsies in 153 women, 30 biopsies were performed on the basis of clinical complaints. One hundred thirty lesions were detected by mammography or sonography or both. Of the 70 lesions recommended for surgical excision, 52 (74%) had documented surgical outcomes. Mammographic surveillance was recommended for 90 lesions, of which 10 (11%) had resolved at the time of this study, 49 (54%) were on track toward 3-year lesion stability, 21 (23%) were being followed up elsewhere, four (4%) were lost to physicians, and six (7%) were lost to follow-up for other reasons. CONCLUSION: Known compliance with follow-up recommendations among these 153 patients who underwent breast core biopsy was higher for patients receiving surgical recommendation (74%) than for patients receiving imaging surveillance recommendation (54%). Problems tracking patients were caused both by loss of patients to follow-up and by incomplete reporting from referring physicians.

Pregnancy, abortion, and birth rates among US adolescents--1980, 1985, and 1990.

OBJECTIVE: To analyze pregnancy, abortion, and birth rates among US adolescent girls in 1980, 1985, and 1990. DESIGN: Retrospective analysis of trends in data on pregnancies, abortions, and births. POPULATION: US adolescent girls aged 13 to 19 years. MAIN OUTCOME MEASURES: Pregnancy, abortion, and birth rates (with and without adjustment for sexual experience) among teenaged girls aged 15 to 19 years and girls under 15 years. RESULTS: Although pregnancy rates among all teenaged girls 15 to 19 years old remained fairly stable from 1980 to 1985, they increased by 9% during the last half of the decade, totaling 95.9 pregnancies per 1000 teenaged girls 15 to 19 years old by 1990. Because rates of sexual experience increased even faster, pregnancy rates among sexually experienced teens aged 15 to 19 actually declined between 1980 and 1990 by approximately 8%. Abortion rates among these teens remained stable during the 1980s, with 35.8 and 36.0 abortions per 1000 in 1980 and 1990, respectively. As with overall pregnancy rates, abortion rates among these sexually experienced teenaged girls declined during the 1980s. Between 1980 and 1985, birth rates among teenaged girls aged 15 to 19 years declined by 4%, but they increased by 18% during the latter half of the decade, totaling 59.9 births per 1000 in 1990. Among these sexually experienced teenagers, birth rates also declined between 1980 and 1985 and then increased over the next 5 years. In 1990, pregnancies and abortions among girls younger than 15 years accounted for only 3% of all adolescent pregnancies and abortions. However, the number of births among these younger adolescents increased by 15% over the decade. In that age group, trends in pregnancy, abortion and birth rates over the decade were similar to those for older teens. However, during the late 1980s, the abortion rate declined and the pregnancy rate remained stable, resulting in a 26% increase in the birth rate. CONCLUSIONS: Despite efforts to reduce adolescent pregnancy in the United States, pregnancy and birth rates for that group continue to be the highest among developed countries. Considering that 95% of adolescent pregnancies are unintended, increased efforts to prevent these pregnancies are warranted.