Neoplasms

Digestive System Diseases

All Conditions

Rare Diseases

Anus Neoplasms

Rectal Neoplasms

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Intestinal Diseases

Anus Diseases

Rectal Diseases

Anal Cancer

Stefania Manfrida, MD

Stefania Manfrida

Stefania Mandrida

Radiochemotherapy is the standard treatment for neoplasms of the anal canal with excellent rates of local control and preservation of the anal sphincter. However, patients may experience a deterioration of quality of life related to sequelae of the treatment particularly at intestinal, anal sphincter and sexual level. Few studies to date have documented patient-reported outcomes (PROs) in this area. The aim of this observational study is to verify the quality of life (QOL) of the patients by means of self-completed questionnaires.

In recent times, the focus on collecting patient-reported outcomes (PROs) has increased in healthcare. The Food and Drug Administration defines PROs as a -measurement of any aspect of a health status of the patient that comes directly from the patient-. These includes disease symptoms, functional aspects and quality of life (QOL). The collection of PROs, combined with physician-assessed toxicity, is constantly being incorporated into clinical practice and studies to provide a more holistic picture of the impact of treatment on patients and prove useful for planning future interventions. Although the use of PROs has now become the standard for measuring quality of life of patients there are still few studies on the self-reported long-term QOL of anal cancer patients and on disease or therapy related symptoms that affect QOL. Therefore, the EORTC (European Organisation for Research and Treatment of Cancer) has recently developed the specific Quality of Life Questionnaire for anal cancer (QLQ-AN27) module to explore typical symptoms of anal cancer and its therapy. In this study, the QLQ-AN27 questionnaire will be administered together with the EORTC Quality of Life 30 (QLQ 30) in patients with anal cancer who have undergone radio-chemotherapy. The questionnaire may be administered before treatment, after treatment and during follow-ups until completion of the fifth year. This is an observational study both retrospective and prospective.

Patient Reported Outcomes (PROs) in Anal Cancer Patient Treated by Intensity Modulated Radiotherapy (IMRT).

Analysis of quality of life (QOL) by administration of PRO questionnaires to patients with cancer of the anus treated with IMRT radiochemotherapy.

Being alive without a temporary or permanent ileostomy or colostomy

Presence of disease progression inside the target volume of radiation therapy

The time from last treatment to cancer recurrence or death from any cause

Acute toxicity caused by chemoradiation according to CTCAE v. 5.0

Late toxicity caused by chemoradiation according to CTCAE v. 5.0

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Symptoms and General Pathology

Nervous System Diseases

Blood and Lymph Conditions

Diseases and Abnormalities at or Before Birth

Recurrence

Glioblastoma

Glioma

Brain Neoplasms

Hemophilia A

Diffuse Intrinsic Pontine Glioma

Astrocytoma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

All Drugs and Chemicals

Antineoplastic Agents

Coagulants

Antibodies

Temozolomide

Lomustine

Immunoglobulins

Mitogens

Factor VIII

ABT-414

Antineoplastic Agents, Alkylating

Alkylating Agents

Immunoconjugates

Immunologic Factors

Depatuxizumab mafodotin (ABT-414) administered once every 2 weeks in combination with temozolomide (TMZ) to adult participants

Depatuxizumab mafodotin (ABT-414) administered once every 2 weeks to adult participants

Adult participants relapsing during temozolomide (TMZ) treatment or within the first 16 weeks after the first day of the last TMZ cycle received lomustine on Day 1 of every 42-day treatment period until one of the treatment withdrawal criteria was met, up to a maximum of 1 year.

Adult participants relapsing 16 weeks or more after the first day of the last temozolomide (TMZ) cycle received TMZ on Day 1 to Day 5 for the first 28-day cycle, with dose escalation in subsequent cycles in case of adequate tolerance and treatment continuing until one of the treatment withdrawal criteria was met.

Depatuxizumab mafodotin (ABT-414) administered once every 2 weeks to pediatric participants. Temozolomide (TMZ) was only allowed for pediatric participants if its use was in accordance with local clinical practice, and was not considered an investigational product for the study (unless this was a local requirement).

Adults: intravenous administration (1.25 mg/kg or 1.0 mg/kg body weight) over 30 to 40 minutes once every 2 weeks until one of the treatment withdrawal criteria was met. The dose was 1.25 mg/kg in the original protocol (Version 1) and Version 2, Amendment 1, and was lowered to 1.0 mg/kg in protocol Version 3, Amendment 2. Pediatric participants: Intravenous administration (1.0 mg/kg body weight for those who were 6 to 17 years old at the date of first dose, or 1.3 mg/kg for those who were 0 to 5 years old) over 30 to 40 minutes or as directed by the guidelines once every 2 weeks until one of the treatment withdrawal criteria was met, for a maximum of one year. If used in combination with temozolomide, depatuxizumab mafodotin was dosed on Day 1 and Day 15 of the TMZ cycle (assuming a standard regimen of 200 mg/m\^2/day for 5 days of each 28-day cycle; for other TMZ schedules, timing of the depatuxizumab mafodotin dosing schedule were to be discussed with the medical monitor).

Depatuxizumab mafodotin

Capsules administered orally, 150 mg/m\^2 on Days 1-5 for the first 28-day cycle, with dose escalation to 200 mg/m\^2 in subsequent cycles in case of adequate tolerance until one of the treatment withdrawal criteria was met.

Capsules administered orally, 110 mg/m\^2 on Day 1 of every 42-day treatment period. Treatment continued until one of the treatment withdrawal criteria was met, for a maximum of one year.

AbbVie Inc.

This study was conducted to evaluate the efficacy and safety of depatuxizumab mafodotin (ABT-414) alone or with temozolomide versus temozolomide or lomustine alone in adult participants with recurrent glioblastoma. The study also included a substudy to evaluate safety, tolerability and pharmacokinetics of ABT-414 in a pediatric population.

The study objectives were to assess whether depatuxizumab mafodotin (ABT-414) alone or in combination with temozolomide (TMZ) improved overall survival (OS), progression-free survival (PFS), tumor response, quality of life, neurological deterioration-free survival (NDFS), and steroid use compared to standard treatment with lomustine single agent or TMZ re-challenge in adult subjects ≥ 18 years of age with centrally-confirmed recurrent epidermal growth factor receptor (EGFR)-amplified glioblastoma. The safety, pharmacokinetics, and efficacy of depatuxizumab mafodotin in children \<18 years of age was evaluated in a pediatric substudy. The EMEA-001732-PIP02-15 pediatric investigation plan was withdrawn on 07 July 2019 due to the discontinuation of the depatuxizumab mafodotin research program.

Adult Study: ABT-414 Alone or ABT-414 Plus Temozolomide vs. Lomustine or Temozolomide for Recurrent Glioblastoma Pediatric Study: Evaluation of ABT-414 in Children With High Grade Gliomas

INTELLANCE-2: ABT-414 Alone or ABT-414 Plus Temozolomide Versus Lomustine or Temozolomide for Recurrent Glioblastoma: A Randomized Phase 2 Study of the EORTC Brain Tumor Group

AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols and clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.

Overall Survival (OS) was defined as time from randomization to death due to any cause, regardless of whether the event occurred on or off study drug (depatuxizumab mafodotin/temozolomide/lomustine).

Progression-free survival was assessed per response assessment in neuro-oncology criteria (RANO) criteria and assessed by an independent review committee and was defined as the length of time during and after the treatment of a disease, that the participant lived with the disease but did not get worse.

The severity of each adverse event was rated according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE Version 4.0)

Cmax is the peak concentration that a drug achieves in a specified compartment after the drug has been administrated and before administration of a second dose.

Cmax is the peak concentration that a drug or drug metabolite achieves in a specified compartment after the drug has been administrated and before administration of a second dose. Cys-mcMMAF is a toxic metabolite of depatuxizumab mafodotin.

Half-life is the calculated time it takes for half of the drug to leave the body.

Half-life is the calculated time it takes for half of the drug or drug metabolite to leave the body. CysmcMMAF is a toxic metabolite of depatuxizumab mafodotin.

AUC is a measure of how long and how much drug is present in the body after dosing. The AUC of depatuxizumab mafodotin (ABT-414) in the pediatric population was measured following treatment to confirm that this was comparable to adults, and that the dosing levels are appropriate for a pediatric population.

AUC is a measure of how long and how much drug or drug metabolite is present in the body after dosing. The AUC of Cys-mcMMAF, a toxic metabolite of depatuxizumab mafodotin, in the pediatric population was measured following treatment to confirm that this was comparable to adults, and that the dosing levels are appropriate for a pediatric population.

The objective response rate (ORR) included best overall responses - complete response (CR) and partial response (PR) - assessed by the independent review committee per response assessment in neurooncology criteria (RANO) criteria from the date of randomization until disease progression or death, whichever came first. All objective responses (CR and PR) must be have been confirmed by repeat MRI 4 weeks after the first time when CR or PR is identified. Any subject who did not meet CR or PR including those who did not have post-baseline radiological assessments was considered a nonresponder.

Overall Survival (OS) was defined as time from randomization to death due to any cause, regardless of whether the event occurred on or off study drug (depatuxizumab mafodotin/temozolomide/lomustine) for all randomized participants that had the Epidermal Growth Factor Receptor (EGFRvIII) mutation.

The pediatric data collection for this study was still ongoing when INTELLANCE-1 (NCT02573324; EudraCT number 2015-001166-26) interim efficacy results overall indicated no survival benefit to adding depatuxizumab mafodotin to standard radiotherapy/temozolomide therapy in newly diagnosed glioblastoma patients. Based on the INTELLANCE-1 results, AbbVie decided to stop further enrollment of pediatric participants into the pediatric substudy and to stop the collection of efficacy data. Because of this decision not to summarize except for safety data, the pediatric substudy ORR analysis was not summarized due to the small number of pediatric participants enrolled in the study.

The pediatric data collection for this study was still ongoing when INTELLANCE-1 (NCT02573324; EudraCT number 2015-001166-26) interim efficacy results overall indicated no survival benefit to adding depatuxizumab mafodotin to standard radiotherapy/ temozolomide therapy in newly diagnosed glioblastoma patients. Based on the INTELLANCE-1 results, AbbVie decided to stop further enrollment of pediatric participants into the pediatric substudy and to stop the collection of efficacy data. Because of this decision not to summarize except for safety data, pediatric time to progression data analysis was not summarized due to the small number of pediatric participants enrolled in the study.

European Organisation for Research and Treatment of Cancer - EORTC

AbbVie

Serious and non-serious adverse events occurring after the subject signed the study-specific informed consent and prior to the initial dose of study drug were to be collected only if they were considered by the Investigator to be causally related to required study procedures.

Depatuxizumab mafodotin (ABT-414) administered once every 2 weeks in combination with temozolomide (TMZ) to adult subjects

ABT-414/Temozolomide

Depatuxizumab mafodotin (ABT-414) administered once every 2 weeks to adult subjects

ABT-414_adult

Adult subjects relapsing during temozolomide (TMZ) treatment or within the first 16 weeks after the first day of the last TMZ cycle received lomustine on Day 1 of every 42-day treatment period until one of the treatment withdrawal criteria was met, up to a maximum of 1 year.

Control_lomustine

Adult subjects relapsing 16 weeks or more after the first day of the last temozolomide (TMZ) cycle received TMZ on Day 1 to Day 5 for the first 28-day cycle, with dose escalation in subsequent cycles in case of adequate tolerance and treatment continuing until one of the treatment withdrawal criteria was met.

Control_ Temozolomide

ABT-414_ Pediatric

Total

Age, Continuous

Sex: Female, Male

American Indian or Alaska Native

Asian

Black or African American

Native Hawaiian or other Pacific Islander

White

Other

Not Reported

Missing

Race/Ethnicity, Customized

Intention-to-treat population (ITT): all randomized participants

Global Medical Services

Stratified at randomization by regions of the world (North America, Europe and Australia, Asia/Other Regions), WHO performance status (0, \> 0), timing of relapse (\< 16 weeks, ≥ 16 weeks after first day of last TMZ cycle).

25th quartile

50th quartile

75th quartile

Adult participants relapsing during temozolomide (TMZ) treatment or within the first 16 weeks after the first day of the last TMZ cycle who received lomustine on Day 1 of every 42-day treatment period until one of the treatment withdrawal criteria was met, up to a maximum of 1 year OR adult subjects relapsing 16 weeks or more after the first day of the last temozolomide (TMZ) cycle who received TMZ on Day 1 to Day 5 for the first 28-day cycle, with dose escalation in subsequent cycles in case of adequate tolerance and treatment continuing until one of the treatment withdrawal criteria was met.

Control (Temozolomide/Lomustine)

All randomized adult participants; participants in the control arms were treated based on the time of relapse and they differ in prognostic profile, therefore data were combined.

Adult Study: Overall Survival (OS)

Adult Study: Progression-Free Survival (PFS)

Pediatric participants (safety population)

Pediatric Study: Percentage of Participants With Adverse Events From the First Visit Until 49 Days After the Last Dose of Study Drug

Pediatric participants with available data

Pediatric Study: Maximum Observed Serum Concentration (Cmax) of ABT-414

Pediatric Study: Maximum Observed Plasma Concentration (Cmax) of Cys-mcMMAF

Pediatric Study: Half-life (t1/2) Observed for ABT-414

Pediatric Study: Half-life (t1/2) Observed for Cys-mcMMAF

Pediatric Study: Area Under the Concentration-time Curve (AUC) Observed for ABT-414

Pediatric Study: Area Under the Concentration-time-curve (AUC) Observed for Unconjugated Cys-mcMMAF

Comparison is based on Cochran-Mantel-Haenszel method with stratification factors. Stratified at randomization by regions of the world (North America, Europe and Australia, Asia/Other Regions), WHO performance status (0, \> 0), timing of relapse (\< 16 weeks, ≥ 16 weeks after first day of last TMZ cycle).

Participants with measurable disease at baseline; participants in the control arms were treated based on the time of relapse and they differ in prognostic profile, therefore data were combined.

Adult Study: Objective Response Rate (ORR)

Randomized adult participants with EGFRvIII-mutated tumors; participants in the control arms were treated based on the time of relapse and they differ in prognostic profile, therefore data were combined.

Adult Study: Overall Survival in the Subgroup With Epidermal Growth Factor Receptor (EGFRvIII) Mutation

Pediatric efficacy data were not collected

Pediatric Study: Objective Response Rate (ORR)

Pediatric Study: Best Tumor Response Rate

Pediatric Study: Duration of Response

Pediatric Study: Overall Survival

Pediatric Study: Time to Progression

Pediatric Study: Progression-Free Survival

Pediatric Study: Percentage of Participants With Changes in Neurological Status and Functioning

Overall Study

Skin and Connective Tissue Diseases

Carcinoma

Breast Neoplasms

Lymphedema

Carcinoma in Situ

Breast Carcinoma In Situ

Breast Diseases

Skin Diseases

Katrine R. Hauerslev, MD

Breast cancer affects a large proportion of Danish women and late morbidity following breast cancer treatment including pain, reduced motility and force of the arm and shoulder, disturbed sensitivity, and lymph edema affects many patients. The risk for such late complications have previously been carefully described by us and others in patients operated by traditional methods, but the follow-up in most of these studies have been rather short , and long time follow-up results are not available. The impact of the new oncoplastic techniques that allows more women to have breast conserving surgery is not known yet. These operations are more extensive and therefore might be accompanied by more complications. The purpose of this study is to give answer to that question.The study includes three parts. First a questionnaire to patients who have breast conserving surgery performed in one of the three breast units in Central Region Denmark. It contains questions regarding arm morbidity, quality of life, comorbidity, and body image. The questionnaire should be filled in preoperatively and 18 months after surgery. The second part consists of an objective evaluation of shoulder and arm function and cosmesis before and after breast conserving surgery with and without oncoplastic techniques. This should be performed at baseline before surgery and 18 months later. The third part is a long time follow-up of patients after breast conserving surgery without oncoplastic techniques. This group of patients is recruited from three breast units in Central Region Denmark. It contains questions regarding arm morbidity, quality of life, comorbidity, and body image. The questionnaire should be filled in preoperatively and 18 months after surgery. The second part consists of an objective evaluation of shoulder and arm function and cosmesis before and after breast conserving surgery with and without oncoplastic techniques. This should be performed at baseline before surgery and 18 months later. The third part is a long time follow-up of patients after breast conserving surgery without oncoplastic techniques. This group of patients is recruited from the cohort in a previous study with 18 months follow-up following breast conserving surgery without oncoplastic technique.

Aims and perspectives:

During the last 20 years there has been increasing focus on the morbidity following breast cancer treatment. This has lead to new and less mutilating surgical techniques to replace the traditional operations: Breast conserving surgery (BCS) instead of mastectomy and sentinel lymph node dissection (SLND) instead of axillary lymph node dissection (ALND). Lately, oncoplastic techniques have been introduced. These techniques further increase the ability to preserve the breast in breast cancer and are expected to increase the cosmetic results compared with traditional techniques, but they are somewhat larger procedures and might therefore lead to increased morbidity after treatment. Hitherto this has not been evaluated in clinical research trials.

The aim of the present study is to examine if oncoplastic techniques in relation to breast cancer treatment have an independent influence on morbidity and quality of life compared to traditional BCS.

In addition, a group of breast cancer patients treated with BCS 10 years ago and who underwent a similar study back then, will be invited to a reevaluation of shoulder function and morbidity.

Background:

Previously, mastectomy was the most applied surgical procedure related to breast cancer. Until the beginning of 1990's it was, by DBCG (Danish Breast Cancer Cooperative Group), recommended as a standard treatment. During the transition towards a more gentle surgical procedure, the use of oncoplastic techniques has been incorporated1,2.

The definition of oncoplastic breast surgery is defined by DBCG as: "a breast conserving procedure, including techniques of plastic surgery, where traditional breast conserving surgery would have lead to a cosmetic unsatisfactory result, and mastectomy would have been the alternative. The requirement for classifying a procedure as oncoplastic is 'the transfer of tissue that requires further skin incision than the breast conserving surgery in its own'3.

The oncoplastic techniques in breast cancer surgery are divided into 3 groups: volume displacement, volume reduction and volume replacement3-5. The oncological results of oncoplastic breast surgery has been evaluated in other studies and found comparable to the oncological results of traditional BCS and mastectomy6.

Increasing evidence have shown that among breast cancer patients a substantial fraction suffer from late symptoms including impairment of shoulder function, pain, disturbance in sensibility, and lymph edema7-9. The sequels are attributable to treatment related factors, including the breast surgical procedure10, axillary dissection11, and radiation therapy12. Studies indicate that sentinel lymph node biopsy (SNLB) reduces shoulder morbidity as compared to ALND11,13, but shoulder impairment also occur after this procedure14.

Recently, the occurrence of late symptoms has been addressed in two Danish publications based on questionnaires7,8 with 2-3 years8 and more than 5 years7 observation, respectively. These studies showed that chronic pain 2-3 years after surgery is a problem in up to 47% of patients of whom 13% suffered from severe and 39% from moderate pain8. More than five years after treatment, chronic pain was recorded in 29% of patients7, and this was associated with poorer quality of life and a higher medicine consumption. Furthermore, a large part of long time survivors reported arm swelling (25%), phantom symptoms (19%), paresthesia (47%), and allodynia (15%)7.

The reported frequency of Lymph oedema following breast cancer treatment vary considerably, probably depending on different definitions and different methods for measurement. As stated earlier, many patients report a subjective feeling of swelling, though the proportion of affected patients seems lower in studies, where objective measures are applied. In a study on node negative patients comparing the results of sentinel node biopsy (SNB) with axillary dissection (ALND)11 up to 18 months after surgery, arm swelling was reported in 7% and 44%, respectively, emphasizing the advantage of the more limited procedure. Using the water displacement method the difference in arm volume between these groups was very modest, although statistically significant. At 18 months, the arm volume on the operated side was 10 ml less than on the non-affected arm in the SNB group, compared with an increase of 28 ml in the ALND group. The water displacement method has been simplified and validated since15,16.

Shoulder morbidity median three years after surgery including ALND was measured in a study on 132 patients (mastectomy 67%, BCT 33%)10. The shoulder function was assessed by the Constant Shoulder Score (CSS), combining subjective symptoms with objective measures of range of motion (ROM) and strengths. Thirty-five percent of the patients had reductions in ROM, in most cases it was flexion and abduction that were most affected. Among these patients CSS was reduced by 12% on the treated side compared with the non-treated shoulder. Patients with normal ROM had comparable CSS on the two sides. In comparison with BCS and radiotherapy, mastectomy combined with postoperative radiation, more often lead to reduced ROM (OR 8.5). In the study by Husted Madsen et al.11 on more recently operated node negative patients, ALND turned out to be significantly associated with a poorer outcome when the dependent variable was the absence or presence of subjective arm and shoulder complaints.

Most studies concerning morbidity, especially those with objective evaluation of patients, have a short follow-up period typically only a few years. No such studies with long-term follow-up up to 5-10 years are available.

A few studies have aimed at describing the effect of physiotherapy on shoulder-arm morbidity13,17, and they have confirmed a better outcome after physiotherapy including general advice and recommendations about how to use and protect the affected arm and instructions for exercises. In the randomized study by Lauridsen et al.13, team instructed physiotherapy consisting of 12 sessions of 60 minutes twice a week instituted between the 6th and 8th postoperative week was compared to the same treatment postponed until the 26th postoperative week. The team instructed physiotherapy commenced early immediately improved the shoulder function, but the same treatment could improve shoulder function significantly even when instituted as long as six months postoperatively.

In a recently published randomized study, Veiga et al.18 have found indications of a better quality of life and self-esteem in BCS including oncoplastic surgery than in patients undergoing traditional BCS. On the other hand, in a study including 101 patients it was found that breast symmetry after BCS had had no effect on quality of life19. In that study symmetry was evaluated by a breast analyzing tool (BAT), one of more available objective measures. Most often, symmetry has been evaluated subjectively by a panel of experts, which has been considered the gold standard. Lately, Cardoso et al. have introduced another objective method where the cosmetic outcome is evaluated semi-automatically from systematic clinical fotos20. They reported a 70% agreement between the expert panel and their measurements. The cosmetic outcome after BCS has been evaluated by Lyngholm et al.21 using the "breast retraction assessment" (BAT) which estimates the symmetry based on measurements on clinical photos22.

The relation between the oncoplastic surgical techniques and shoulder disability, chronic pain, and lymph edema has hitherto not been systematically investigated, but some attempts have been made to describe the impact on shoulder function of post-mastectomy reconstructive surgery. In a study from Sweden23, shoulder function after reconstructive procedures involving the latissimus dorsi flap was examined. The main finding was that the reconstruction lead to an insignificant increase in long-term shoulder morbidity, but it was also noted that a small subset of patients developed long-term impairment.

Design and methods:

The study includes three parts:

1. A questionnaire describing the occurrence of loco-regional morbidity in patients who has undergone breast conserving surgery with and without oncoplastic techniques.
2. Objective evaluation of shoulder and arm function and cosmesis before and after breast conserving surgery with and without oncoplastic techniques.
3. Long time follow-up of patients after breast conserving surgery without oncoplastic techniques.

Part 1

The questionnaire combines previous used and validated forms addressing shoulder and arm function, pain, sensibility, cosmesis and body image, and QoL. The questionnaire should be filled in preoperatively and 18 months after surgery. Patients included in the longtime follow-up study described below are asked to answer the same questionnaire, which includes questions about the following:

* Arm morbidity: Pain, sensibility, swelling, restriction of movements, force
* Quality of life (EORTC QLQ-C30 and QLQ-BR23)
* Comorbidity - Charlsons Comorbidity Index
* Body Image
* Physiotherapy Part 2

Cohort study with 18 months follow-up. Patients are evaluated at baseline before surgery and after 18 months with the following methods:

* Passive Range of movement (pROM). The passive motion of both shoulders are measured in supine position by use of a goniometer: flexion, extension, abduction, inner and outer rotation
* Constant Shoulder Score (CSS). Including active Range of movement (aROM) in flexion, abduction, rotation and strengths during shoulder abduction in upright standing position with the IsoForceControl dynamometer
* Sensibility recording
* Arm circumference
* Arm volume - simplified water displacement method
* Cosmetic outcome - using clinical photos of the breast region (frontal- and side view) and estimation of BRA (Breast Retraction Assessment) Re. part 1 and 2

Inclusion:

Patients, who are undergoing breast conserving surgery for invasive breast cancer or carcinoma in situ by one of the three breast surgical units at hospitals in Central Denmark Region (Viborg, Randers, and Aarhus). They will be divided in the two groups:

* BCS including oncoplastic surgical techniques
* BCS without oncoplastic surgical techniques

Exclusion:

* Patients who are unable to sign an informed consent form
* Patients above the age of 75 years and under the age of 18 years.
* Patients who have previously been operated in the same or the contralateral breast, shoulder or arm Part 3 The study performed by Husted Madsen et al. in 2003-4 included in all 395 patients. Surviving patients from this cohort are asked to e new evaluation of shoulder and arm function following the same procedure as described in Part 1 and 2.

Statistics:

Based on previous experience and statistical calculations estimated that the investigators need 495 to participate in the questionnaire (Part 1) and 220 patient for the objective evaluation (Part 2) Further details can be added If requested.

Ethics:

Patients included in part 1 and 2 will be contacted in the breast units after confirmation of the diagnosis and after decision about the treatment has been made. Before inclusion oral and written information about the study are given and the patient is asked to sign an informed consent form. For part 3 of these studies, patients receive a letter invitation and these patients are also asked to sign an informed consent form before entering the study.

There is only minor discomfort associated with the objective evaluation and no major complications or side effects are expected.

The protocol is submitted to The Local Research Ethics Committee for Central Region Denmark for approval.

Shoulder Disability and Late Symptoms Following Oncoplastic Breast Surgery

Estimating arm lympoedema by the water displacement method and breast lymphoedema by clinical evaluation.

Comparing cosmetic results by clinical evaluation and photos including breast retraction assessment (BRA)

By measuring passive and active range of movement (ROM) in the shoulder, measuring strength by a dynamometer (IsoForceControl). Estimating Constant Shoulder Score.

Comparing EORTC QLQ-c30 and br23 before and 18 months after surgery.

Danish Cancer Society

University of Aarhus

Immune System Diseases

Gland and Hormone Related Diseases

Behaviors and Mental Disorders

Lymphoma, Large B-Cell, Diffuse

Lymphoma

Lymphoma, B-Cell

Hypogonadism

Gonadal Disorders

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Endocrine System Diseases

Quality of Life

B-cell Lymphoma

Diffuse Large B-Cell Lymphoma

Lymphosarcoma

Oculocerebral Syndrome With Hypopigmentation

Doxorubicin

Liposomal doxorubicin

Testosterone

This study is an observational cross-sectional study which aims to investigate the relationship between treatment with chemotherapy and the development of low levels of testosterone in the blood in patients cured for aggressive lymphoma. We hypothesize that patients in turn will develop sexual dysfunction and poor quality of life because of this reduced level of testosterone. Cancer treatment is increasingly effective and the overall survival higher, which makes issues like sexuality and long-term quality of life more and more important to address in cured cancer patients. Patient sexuality and quality of life is measured by 3 questionnaires filled out once, and serum testosterone by a single blood sample. If serum testosterone is in the lower part of the normal reference interval, patients will be offered further hormonal evaluation by department of growth and reproduction at Copenhagen University Hospital. We hope to show that future follow up visits should include focus on sexuality and serum testosterone. Questionnaires and blood samples can be implemented easily and without great cost.

Diffuse large B-cell lymphoma and Hodgkin Lymphoma are two aggressive lymphomas often treated with doxorubicin containing chemotherapy. Doxorubicin is an anthracycline and is known to be toxic to both Leydig Cells of the testes and hormone-producing cells of the hypothalamus. Therefore patients treated with this drug are at risk of developing hypogonadism. Standard follow-up programs do not include investigation of hormone levels. With this study we aim to investigate the extent of hypogonadisme in patients treated with anthracycline containing chemotherapy, to clarify whether it is relevant to include serum testosterone in standard follow-up programs.

Our Hypothesis:

Hypothesis 1: A significant proportion of long-term male survivors of HL and DLBCL have impaired QoL due to sexual dysfunction.

Hypothesis 2: A significant proportion of long-term male survivors of HL and DLBCL have reduced levels of testosterone.

Hypothesis 3: A significant relationship between QoL, sexual dysfunction and testosterone levels exists.

To clarify the extent of hypogonadisme a single blood test including s-total-testosterone will be drawn once, and levels below age adjusted reference levels will be classified as hypogonadisme. To assess patients sexuality and quality of life, 3 questionnaires will be filled out; the EORTC QLQ-C30 for general quality of life, EORTC SHQ-22 for sexual health and IIEF-5 for sexual function.

To evaluate whether normal reference levels are sufficient in the examination of lymphoma survivors, included men with serum testosterone in the lower part of the normal reference interval will be offered further hormonal evaluation at the department of growth and reproduction at Copenhagen University hospital. Blood test results will be evaluted by this research group.

Gonadal Dysfunction in Male Long-term Survivors of Malignant Lymphoma; Vitality-Obs

Vitality-Obs; An Observational and Descriptive Cross-sectional Study of Gonadal Dysfunction in Male Long-term Survivors of Malignant Lymphoma

The frequency of sexual dysfunction measured by serum-testosterone level below age adjusted reference levels, in patients with DLBCL or HL.

According to SHQ-22 symptom scores. High symptoms scores represents high level of symptoms.

According to SHQ-22 function scores. High symptoms scores represents high level of functioning.

According to QLQ-C30 function scores. High function scores represents a high level of functioning.

According to QLQ-C30 symptoms scores. High symptoms scores represents high level of symptoms.

According to QLQ-C30 global health scores. High symptoms scores represents high level of global health.

The frequency of serum SHBG levels above the reference level

The frequency of serum LH levels above the reference level

The frequency of serum Inhibin B levels below the reference level

The frequency of serum FSH levels above the reference level

The frequency of serum estradiol levels above the reference level

The frequency of serum estradiol levels below the reference level

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Patient Reported Outcomes (PROs) in Anal Cancer Patient Treated by Intensity Modulated Radiotherapy (IMRT).	NCT06364579	Anal Cancer Pat...		18 Years -	Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Patient Reported Outcomes (PROs) in Anal Cancer Patient Treated by Intensity Modulated Radiotherapy (IMRT).	NCT06364579	Anal Cancer Pat...		18 Years -	Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Adult Study: ABT-414 Alone or ABT-414 Plus Temozolomide vs. Lomustine or Temozolomide for Recurrent Glioblastoma Pediatric Study: Evaluation of ABT-414 in Children With High Grade Gliomas	NCT02343406	Glioblastoma	Depatuxizumab m... Temozolomide Lomustine	- 99 Years	AbbVie
Adult Study: ABT-414 Alone or ABT-414 Plus Temozolomide vs. Lomustine or Temozolomide for Recurrent Glioblastoma Pediatric Study: Evaluation of ABT-414 in Children With High Grade Gliomas	NCT02343406	Glioblastoma	Depatuxizumab m... Temozolomide Lomustine	- 99 Years	AbbVie
Shoulder Disability and Late Symptoms Following Oncoplastic Breast Surgery	NCT02159274	Breast Cancer Carcinoma in Si...		18 Years - 75 Years	University of Aarhus
Gonadal Dysfunction in Male Long-term Survivors of Malignant Lymphoma; Vitality-Obs	NCT04630275	Hypogonadism		18 Years - 65 Years	Herlev Hospital
An EORTC Study Updating the QLQ-BR23 to BR45	NCT04270123	Cancer Breast Cancer	EORTC QLQ-BR45 ...	18 Years -	University of Leeds
Gonadal Dysfunction in Male Long-term Survivors of Malignant Lymphoma; Vitality-Obs	NCT04630275	Hypogonadism		18 Years - 65 Years	Herlev Hospital
Gonadal Dysfunction in Male Long-term Survivors of Malignant Lymphoma; Vitality-Obs	NCT04630275	Hypogonadism		18 Years - 65 Years	Herlev Hospital
An EORTC Study Updating the QLQ-BR23 to BR45	NCT04270123	Cancer Breast Cancer	EORTC QLQ-BR45 ...	18 Years -	University of Leeds

Spots Global Cancer Trial Database for eortc

Every month we try and update this database with for eortc cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for eortc

Every month we try and update this database with for eortc cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for eortc cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.