ABSTRACT
Background: Recent data have demonstrated that in locally advanced rectal cancer (LARC), a total neoadjuvant therapy (TNT) approach improves compliance with chemotherapy and increases rates of tumor response compared to neoadjuvant chemoradiation (CRT) alone. They further indicate that the optimal sequencing of TNT involves consolidation (rather than induction) chemotherapy to optimize complete response rates. Data, largely from retrospective studies, have also shown that patients with clinical complete response (cCR) after neoadjuvant therapy may be managed safely with the watch and wait approach (WW) instead of preemptive total mesorectal resection (TME). However, the optimal consolidation chemotherapy regimen to achieve cCR has not been established, and a randomized clinical trial has not robustly evaluated cCR as a primary endpoint. Collaborating with a multidisciplinary oncology team and patient groups, we designed this NCI-sponsored study of chemotherapy intensification to address these issues and to drive up cCR rates, to provide opportunity for organ preservation, improve quality of life for patients and improve survival outcomes. Methods: In this NCI-sponsored multi-group randomized, seamless phase II/III trial (1:1), up to 760 patients with LARC, T4N0, any T with node positive disease (any T, N+) or T3N0 requiring abdominoperineal resection or coloanal anastomosis and distal margin within 12 cm of anal verge will be enrolled. Stratification factors include tumor stage (T4 vs T1-3), nodal stage (N+ vs N0) and distance from anal verge (0-4; 4-8; 8-12 cm). Patients will be randomized to receive neoadjuvant long course chemoradiation (LCRT) followed by consolidation doublet (mFOLFOX6 or CAPOX) or triplet chemotherapy (mFOLFIRINOX) for 3-4 months. LCRT in both arms involves 4500 cGy in 25 fractions over 5 weeks + 900 cGy boost in 5 fractions with a fluoropyrimidine (capecitabine preferred). Patients will undergo assessment 8-12 (+/- 4) weeks post-TNT completion. The primary endpoint for the phase II portion will compare cCR between treatment arms. A total number of 296 evaluable patients (148 per arm) will provide statistical power of 90.5% to detect an 17% increase in cCR rate, at a one-sided alpha=0.048. The primary endpoint for the phase III portion will compare disease-free survival (DFS) between treatment arms. A total of 285 DFS events will provide 85% power to detect an effect size of hazard ratio 0.70 at a one-sided alpha of 0.025, requiring enrollment of 760 patients (380 per arm). Secondary objectives include time-to event outcomes (overall survival, organ preservation time and time to distant metastasis) and adverse effects. Biospecimens including archival tumor tissue, plasma and buffy coat in EDTA tubes, and serial rectal MRIs will be collected for exploratory correlative research. This study, activated in late 2022, is open across the NCTN and has a current accrual of 312. Support: U10CA180821, U10CA180882, U24 CA196171; https://acknowledgments.alliancefound.org . Discussion: Building off of data from modern day rectal cancer trials and patient input from national advocacy groups, we have designed the current trial studying chemotherapy intensification via a consolidation chemotherapy approach with the intent to enhance cCR and DFS rates, increase organ preservation rates, and improve quality of life for patients with rectal cancer. Trial Registration: Clinicaltrials.gov ID: NCT05610163 ; Support includes U10CA180868 (NRG) and U10CA180888 (SWOG).
ABSTRACT
BACKGROUND: Extent of peritoneal metastases (PM) is among the most powerful prognostic factors for survival after cytoreductive surgery (CRS). This study aimed to compare the Peritoneal Cancer Index (PCI) and the Dutch region count as tools for staging PM of colorectal cancer. The Dutch region count is a simpler classification that distinguishes seven rather than 13 abdominal regions. Presence or absence of PM is recorded. METHODS: This was a retrospective cohort study in two tertiary referral centres in the Netherlands. Consecutive patients with colorectal PM who were intentionally treated with CRS and subsequent hyperthermic intraperitoneal chemotherapy in 2016 and 2017 were included. The PCI and Dutch region count were both recorded during laparotomy. Correlation between scoring tools was calculated using Spearman's rank correlation coefficient. Diagnostic values were calculated for different cut-off values of the PCI, alongside the Dutch region count. The correlation of both scores was determined for the exploration and validation cohorts separately. RESULTS: In the exploration and validation cohorts, 73 and 85 patients respectively were included. Spearman's correlation coefficients of 0·897 and 0·961 were observed for continuous scores of the Dutch region count and PCI in the exploration and validation group respectively. A cut-off value of 20 for the PCI score and 5 for the Dutch region count showed 91·9 and 94·5 per cent sensitivity, and 81·8 and 91·7 per cent specificity, respectively. CONCLUSION: The Dutch region count correlated well with the PCI score, and may help to simplify reporting of the extent of peritoneal disease.
ANTECEDENTES: La extensión de las metástasis peritoneales (peritoneal metastases, PM) es uno de los factores pronósticos más importantes para la supervivencia después de la cirugía citorreductora (cytoreductive surgery, CRS). El objetivo de este estudio fue comparar el índice de carcinomatosis peritoneal (Peritoneal Cancer Index, PCI) y el recuento holandés por regiones como herramientas para la estadificación de las PM del cáncer colorrectal. El recuento holandés por regiones es una clasificación más simple que distingue 7 regiones abdominales en lugar de 13. En dichas regiones abdominales se registró la presencia o ausencia de PM. MÉTODOS: Se llevó a cabo un estudio de cohortes retrospectivo en dos centros de referencia terciarios en los Países Bajos. Se incluyeron pacientes consecutivos con PM de origen colorrectal que fueron tratados con CRS seguida de quimioterapia intraperitoneal hipertérmica (hyperthermic intraperitoneal chemotherapy, HIPEC) en 2016 y 2017. Durante la laparotomía se recogieron datos del índice PCI y de la clasificación de las regiones abdominales. Se utilizó el coeficiente de correlación de Spearman para analizar la correlación entre estas dos herramientas de puntuación. Se calculó la precisión diagnóstica en función de diferentes umbrales del índice PCI junto con los datos del recuento por regiones. Asimismo, se calcularon las correlaciones entre ambas puntuaciones en las cohortes de exploración y validación por separado. RESULTADOS: Se incluyeron 73 pacientes en la cohorte de exploración y 85 en la de validación. Los coeficientes de correlación de Spearman eran de 0,987 para puntuaciones continuas del recuento holandés por regiones abdominales y del PCI en la cohorte de exploración y de 0,961 en la cohorte de validación. Los umbrales de corte de 20 para el índice PCI y de 5 para el recuento por regiones demostraron sensibilidades de 91,9% y 94,5%, y especificidades de 81,8% y 91,7%, respectivamente. CONCLUSIÓN: El recuento holandés por regiones abdominales se correlacionó bien con el PCI y puede ser útil para simplificar la extensión de la enfermedad peritoneal.
ABSTRACT
The current study was a 7-year follow-up of 74 6-12 year old children with Pervasive Developmental Disorder-Not Otherwise Specified. We examined the rates and 7 year stability of comorbid psychiatric diagnoses as ascertained with the Diagnostic Interview Schedule for Children: Parent version at ages 6-12 and again at ages 12-20. Also, we examined childhood factors that predicted the stability of comorbid psychiatric disorders. The rate of comorbid psychiatric disorders dropped significantly from childhood (81 %) to adolescence (61 %). Higher levels of parent reported stereotyped behaviors and reduced social interest in childhood significantly predicted the stability of psychiatric comorbidity. Re-evaluation of psychiatric comorbidity should be considered in clinical practice, since several individuals shifted in comorbid diagnoses.
Subject(s)
Child Development Disorders, Pervasive/epidemiology , Mental Disorders/epidemiology , Child , Child Development Disorders, Pervasive/diagnosis , Child, Preschool , Comorbidity , Female , Follow-Up Studies , Humans , Male , Mental Disorders/diagnosisABSTRACT
The current 7-year follow-up study investigated: (1) the stability of ASD severity, and (2) associations of ASD severity in adolescence with (a) childhood and concurrent psychiatric comorbidity, and (b) concurrent societal functioning. The Autism Diagnostic Observation Schedule (ADOS) and the Diagnostic Interview Schedule for Children were administered in childhood (ages 6-12) and in adolescence (ages 12-20) to 72 individuals with a pervasive developmental disorder-not otherwise specified (PDD-NOS). ADOS calibrated severity scores showed a large stability (r = .51). Psychiatric comorbidity in childhood and adolescence were not associated with ASD severity in adolescence. Mental health care use (87 %) and special education needs were high (71 %). Reevaluation of ASD severity and psychiatric comorbidity later in life seem useful when PDD-NOS is diagnosed in childhood.
Subject(s)
Child Development Disorders, Pervasive/epidemiology , Adolescent , Child , Child Development Disorders, Pervasive/diagnosis , Child Development Disorders, Pervasive/psychology , Comorbidity , Female , Humans , Male , Social Behavior , Young AdultABSTRACT
BACKGROUND: A recent survey amongst 48 key figures from all 51 Dutch institutions for youth mental health care service confirmed the hypothesis that counselling in the Dutch youth mental health care service hardly ever follows a standard pattern. In their reactions to this survey, professionals seem to be strongly in favour of a methodical form of counselling that is firmly based on scientific principles. Based on this survey, a review of the literature and panel discussions, an evidence-based counseling procedure for the youth mental health care was developed.
Subject(s)
Adolescent Psychiatry/standards , Child Psychiatry/standards , Counseling/organization & administration , Mental Health Services/standards , Adolescent , Child , Counseling/standards , Evidence-Based Medicine/methods , Female , Health Care Surveys , Humans , Male , NetherlandsABSTRACT
BACKGROUND: Up till the 1970s child and adolescent psychiatry had no distinctive diagnostic system of its own. From the 1980s onwards qualitative information-gathering (e.g. via discussion or play-situations) was no longer regarded as adequate and the standardised gathering of (quantitative) information became the cornerstone of the diagnostic process. This development fundamentally changed the child psychiatrist's profession and its identity. AIM: To investigate the specific features that are required in current child and adolescent psychiatry. METHOD: In this article we will clarify the change in the child psychiatrist's profession and identity by outlining how child an adolescent psychiatry evolved as from the early 1980s. We will do this by concentrating on the diagnostic process. The treatment aspect will be discussed only briefly. RESULTS: Over the last 25 years the role of the child psychiatrist has undoubtedly changed. From being mainly a diagnostician and/or being personally responsible for treating the child or adolescent the child psychiatrist has become increasingly the person who controls the diagnostic process and plans treatment. CONCLUSION: Over the last two decades the diagnostic technique of the child psychiatrist has developed in a new direction. The child psychiatrist has chosen instead to elucidate a patient's referral and to discuss the reasons for a request for assistance and/or care. The psychiatrist uses many types of information and a multitude of informants and methods. This development has led to a fundamental change in the child psychiatrist's profession and its identity.
Subject(s)
Adolescent Psychiatry/methods , Child Psychiatry/methods , Mental Disorders/diagnosis , Adolescent , Adolescent Psychiatry/standards , Child , Child Psychiatry/standards , Child, Preschool , Diagnosis, Differential , Female , Humans , International Classification of Diseases , Male , Pediatrics , Psychiatric Status Rating ScalesABSTRACT
Diagnosis and classification of autism and related pervasive developmental disorders is both easy and difficult. Infantile autism is a characteristic syndrome on which many publications have appeared in the last 50 years. Conversely, the diagnosis and even the classification of children with pervasive developmental disorders related to autism is difficult. Although children with these disorders are twice as numerous as children with infantile autism, growing attention has been directed to at the latter group since the last decade. In this paper, autism and related disorders are described as a developmental disorder as well as a spectrum disorder. The spectrum of clinical symptoms can be explained, of which infantile autism is the most severe and prototypical manifestation. A working model is presented which accounts for all the problems of children with pervasive developmental disorders. An illustration of working with the model in practice is also given. The main lines of treatment and stages in treatment are briefly described.
Subject(s)
Child Development Disorders, Pervasive/classification , Child Development Disorders, Pervasive/therapy , Autistic Disorder/classification , Autistic Disorder/physiopathology , Autistic Disorder/therapy , Child , Child Development Disorders, Pervasive/physiopathology , HumansABSTRACT
Autism and mental retardation are concepts of a different level. The combination of these concepts in the mentally retarded autistic child requires a specific therapeutic environment. This therapeutic environment must take full account of both the child's limited cognitive potentials and the specific needs and limitations on the basis of autism. Such an integrated approach of the mentally retarded autistic child becomes possible when all the symptoms and behaviours of the children are organized in one coherent frame of reference organized according to the main axes of child development (biological, physical, cognitive and socio-emotional). The consequences of these partly dissimilar, divergent needs and limitations of mentally retarded autistic children for the planning of a therapeutic environment are discussed. Special attention is paid to the combined effect of mental retardation and autism on the cognitive development axes.
Subject(s)
Autistic Disorder/rehabilitation , Intellectual Disability/rehabilitation , Residential Treatment , Social Environment , Autistic Disorder/psychology , Child , Child Development , Education of Intellectually Disabled , Humans , Intellectual Disability/psychologyABSTRACT
Formulated from a cognitive frame of reference, psychodynamic therapy can be viewed as acting on one of the three aspects (feeling, thought, action) in order to influence or change the client's action and thought schemes. In this paper the consequences of the interaction of cognition and emotion for psychotherapeutic practice with adolescents are explored. Knowledge of cognitive development is supposed to be important for the therapist because, from Piaget's viewpoint, the structures of affect are cognitive structures. Moreover a great variability exists in cognitive development between adolescents. This variability is due to individual, family and social variables. The cognitive structural developmental model, the relation between emotional and cognitive development and the afore-mentioned variables are discussed. Consequences are psychotherapeutic practice with adolescents are described and short case histories are given. The authors conclude that in psychotherapeutic practice psychodynamic theory and cognitive structural theory can complete each other.
Subject(s)
Cognition , Mental Disorders/therapy , Psychotherapy , Adaptation, Psychological , Adolescent , Environment , Humans , Intelligence , Mental Disorders/psychology , Models, Psychological , Psychology, Adolescent , Self ConceptABSTRACT
Although its history in Netherlands is a short one, day treatment for children and adolescents is in great demand and an increase in the number of centers throughout the country has been planned. It serves as both a primary and a secondary treatment modality. While the theoretical frames of reference among day units vary, psychoanalytic and systems thinking are the leading orientations. All day units operate with a multidisciplinary staff who work intensively and therapeutically with the children and their families. The day unit at Sophia Children's Hospital in Rotterdam is described as an example of an existing program.
