Cancer is a disease of the elderly (average age of onset >69yrs). However, there is few data available on treatment- and disease-related interactions with the functional reserve of these patients (pts). Prospective, multicenter non-interventional trial at two university hospitals in Germany. Included were pts ≥ 75yrs (n = 30) with gastrointestinal tumors receiving chemotherapy “ctx” in the period Q1/2015 - Q1/2016. To objectify the functionality of these pts sequential geriatric assessments (G8-Questionaire, ECOG, IADL, ADL) were performed. The analysis is based on data from 2 patient cohorts (C1: ctx <2wks, n = 15; C2: ctx >8 wks, n = 15). An initial dose reduction tended to stabilize the ADL/IADL of pts with newly initiated ctx (C1) when compared to those pts who received a 100%-dosage initially (p = 0,0986). Less ≥2° toxicities (tox) were detected after initial dose reduction (p = ns). However, at the time of the analysis the tox did not correlate with a deterioration in the IADL or ADL. Pts who started ctx with a pathological G8-Screening (<14) functionally improved over the period of the analysis (p = ns). The disease control rate (PR + SD) had a sign impact on the functionality of these pts (ADL: p = 0,0195). In contrast, for pts receiving ctx > 8 wks (C2), a continued 100%-dosage did not result in a deterioration in the ADL/IADL (additionally no correlation between tox and the IADL/ADL has been detected). C2 pts with an intial G8 < 14 showed no further improvement, however pts with a G8-score ≥14 tended to reach a better functional performance over time (IADL/ADL: p = 0,0986). Furthermore for C2 pts disease control (PR + SD) was also significantly associated with a functional improvement (G8/ECOG: p = 0,0003; ADL: p = 0,0261). These data suggest, that dose-escalating strategies maintain the functional reserve of pts ≥75yrs with gastrointestinal tumors. However disease control was the strongest predictor for stabilized functionality.

Fragestellung: Kommunikation über Therapiebeschränkung ist ein wesentliches Element der Zusammenarbeit im interdisziplinären Team auf Intensiv- und Palliativstationen. Ziel der Untersuchung war, Aspekte der Kommunikation im Kontext von Therapiebeschränkungen (TB) und Burnout bei den Mitarbeitern beider Stationen zu vergleichen. Methode: Mitarbeiterbefragung auf Intensivstationen (ITS, 72 Betten) und Palliativstation (PS, 12 Betten). Der Fragebogen enthielt das Maslach Burnout Inventar (MBI) und 40 selbst entwickelte Fragen zu Kommunikation und Zusammenarbeit. Es wurde ein 2:1 Propensity Score Matching von ITS- und PS-Mitarbeitern nach demografischen Variablen durchgeführt. Ergebnisse: Von insgesamt 191 Fragebögen (Rücklauf 60 %) und nach Matching wurden Antworten von 29 (ITS-) und 15 (PS-Mitarbeitern) analysiert. Bei 21 % der ITS-Mitarbeiter, aber keinem PS-Mitarbeiter, war ein erhöhtes Burnout-Risiko gegeben (p = 0,08). ITS-Mitarbeiter werteten die Interaktion im Team, die Rollenklarheit im Kontext von TB und die emotionale Unterstützung signifikant schlechter als PS-Mitarbeiter. Dies war vor allem darauf zurückzuführen, dass ITS-Pflegekräfte hier signifikant schlechter werteten als ITS-Ärzte, während es zwischen den PS-Ärzten und -Pflegekräften keine Unterschiede gab. Bezüglich der Kommunikation zu TB waren ITS-Mitarbeiter seltener zufrieden (42 vs. 80 %; p = 0,025), insbesondere waren ITS-Pflegekräfte seltener zufrieden als -Ärzte (11 vs. 67 %; p = 0,013), bei den PS-Mitarbeitern gab es keine Unterschiede. Schlussfolgerungen: Die Unterschiede in der Bewertung von Aspekten der Kommunikation zwischen Ärzten und Pflegekräften nur auf der Intensivstation, nicht auf der Palliativstation, sind durch unterschiedliche Arbeitsanforderungen allein nicht zu erklären. Interventionen zur Verbesserung der Zusammenarbeit auf ITS sind zu empfehlen, die sich an der Kommunikationskultur auf Palliativstationen orientieren.

Aim: Communication about end-of-life decisions (EOL-D) is essential for interdisciplinary teamwork on intensive care and palliative care units. The aim of this study was to compare aspects of communication in the EOL-D context and burnout of staff on these units.Methods: Survey among staff of intensive care units (ICU, 72 beds) and a palliative care unit (PCU, 12 beds). The questionnaire consisted of the Maslach Burnout Inventory (MBI) and 40 self-developed questions on communication and teamwork. 2:1 propensity score matching of ICU and PCU staff was performed according to demographic characteristics.Results: Response rate was 60 % (191 questionnaires). After matching, 29 (ICU) and 15 (PCU) responses were analysed. 21 % of ICU but none of the PCU staff members were at risk for burnout (p = 0.08). Work demands were similar, but interaction within the team, role clarity in the context of EOL-D and emotional support were rated worse on ICUs. This was mostly due to the fact that ICU nurses gave significantly worse ratings than ICU physicians, whereas PCU nurses and physicians gave similar ratings. Satisfaction with communication in the context of EOL-D was lower among ICU staff (42 % vs. 80 %; p = 0.025). Particularly ICU nurses where less satisfied than ICU physicians (11 % vs. 67 %, p = 0.013). There was no such difference among PCU staff.Conclusion: The differences between nurses’ and physicians’ ratings of communication which were found on the ICU but not on the palliative care unit cannot be explained only by a different work load. To improve interdisciplinary teamwork on the ICU, interventions may be advisable which can be modelled on the communication culture practiced on palliative care units.

Inhalt 1. Informationen zu dieser Leitlinie 462 1.1. Herausgeber 462 1.1.1. Federführende Fachgesellschaft 462 1.1.2. Kontakt 462 1.1.3. Verfügbare Dokumente zur Leitlinie 462 1.2. Besonderer Hinweis 462 1.3. Autoren dieser Leitlinie 462 1.4. Ziele des Leitlinienprogramms Onkologie 462 2. Einführung 463 2.1. Geltungsbereich und Zweck 463 2.1.1. Zielsetzung und Fragestellung 463 2.1.2. Adressaten 464 2.1.3. Verbreitung u. Implementierung d. Leitlinien 464 2.1.4. Finanzierung der Leitlinie und Darlegung möglicher Interessenskonflikte 464 2.1.5. Gültigkeitsdauer u. Aktualisierungsverfahren 465 2.2. Grundlagen der Methodik 465 2.2.1. Schema der Evidenzgraduierung nach Oxford 465 2.3. Verwendete Abkürzungen 466 3. Konsentierte und abgestimmte Empfehlungen 466 3.1. Risikofaktoren 466 3.1.1. Helicobacter pylori 466 3.1.2. Weitere Risikofaktoren 467 3.2. Risikogruppen 468 3.2.1. Familiäres Risiko 468 3.2.2. Hereditäres nonpolypöses kolorektales Karzinom (HNPCC) 469 3.3. Screening und Prävention 470 3.3.1. Screening 470 3.3.2. Prävention 471 3.4. Primärdiagnostik 472 3.4.1. Endoskopische Untersuchung 472 3.4.2. Staging 472 3.4.3. Histologie 472 3.5. Staging 473 3.5.1. Ultraschalldiagnostik 473 3.5.2. Röntgendiagnostik 474 3.5.3. Laparoskopie 475 3.5.4. Laborchemische Parameter 476 3.6. Histopathologie 476 3.7. Endoskopische Therapie 477 3.7.1. Resektion 477 3.7.2. Rezidiv 479 3.7.3. Komplikationen 479 3.7.4. Nachsorge 479 3.8. Chirurgische Therapie 479 3.8.1. Resektion 479 3.8.2. Rezidiv 483 3.8.3. Definitive Radiochemotherapie 483 3.9. Multimodale Therapie 483 3.9.1. Perioperative Chemotherapie 483 3.9.2. Präoperative Radiochemotherapie 488 3.9.3. Präoperative Antikörper-Therapie 488 3.9.4. Restaging nach neoadjuvanter Therapie 488 3.9.5. Postoperative Therapie 489 3.9.6. Adjuvante Therapiekonzepte 491 3.10. Tumorgerichtete palliative Therapie 493 3.10.1. Medikamentöse Tumortherapie 493 3.10.2. Vorgehen bei Tumoren ohne HER-2-Überexpression 494 3.10.3. Vorgehen bei HER-2-überexprimierenden/-amplifizierenden Tumoren 498 3.10.4. Zweit-Chemotherapie 498 3.11. Weitere palliative Situationen u. deren Therapie 499 3.11.1. Palliative Therapieoptionen 499 3.11.2. Therapie der Tumorblutung 500 3.11.3. Palliative operative Therapie 500 3.11.4. Chemotherapie-refraktärer maligner Aszites 500 3.12. Supportive Maßnahmen 501 3.12.1. Fatigue-Syndrom 501 3.12.2. Zusammenfassung weiterer Maßnahmen 501 3.13. Ernährung 505 3.13.1. Allgemeine Entscheidungshilfen 505 3.13.2. Präoperative Ernährungstherapie 506 3.13.3. Postoperative Ernährungstherapie 507 3.13.4. Ernährung unter Chemotherapie oder Strahlentherapie 507 3.13.5. Ernährung in der Sterbephase 509 3.14. Nachsorge und Rehabilitation 509 3.14.1. Lebensqualität 509 3.14.2. Substitutionen nach Gastrektomie 509 3.14.3. Rehabilitationsmaßnahmen 509 3.14.4. Bestimmung von Tumormarkern 510 3.15. Psychoonkologie 510 3.15.1. Patientennahes Informationsmanagement 510 3.15.2. Lebensqualität 510 3.15.3. Psychoonkologische Betreuung 511 3.16. Komplementäre Therapie 512 3.16.1. Abgestimmte Empfehlungen 512 3.16.2. Weitere Hinweise der Arbeitsgruppe zur komplementären Therapie 514 4. Qualitätsindikatoren 515 Literatur 517

1070 Background: PELICAN is a randomized phase III trial evaluating efficacy and safety of pegylated liposomal doxorubicin (PLD) vs. capecitabine (CAP) as first-line therapy in patients (pts) with MBC. CGA results and correlation to time to progression (TTP), overall survival (OS), and time to treatment failure (TTF) were evaluated. Methods: CGA comprised data on activities of daily living (ADL), instrumental sctivities of daily living (IADL), Karnofsky performance status (KPS), comorbidity (CIRS-G), and the number of comedications. According to CGA, pts were classified into 3 groups. Single and combined CGA items were analyzed for association with treatment burden and efficacy outcome (TTP, OS, TTF) using Fisher's exact test, Wilcoxon test, and logistic regression. Results: Data from 210 pts (105 PLD, 105 CAP) with a median age of 62 y (22-85) were analyzed. 123 pts (59%) were <65 y and 87 pts (41%) ≥65 y. CGA scores were available from 152 pts. According to CGA, 113 pts were considered fit (group 1, 74%), 15 compromised (group 2, 10%), and 24 frail (group 3, 16%). Pts with a good KPS (≥ 90%) (n=46) had a significantly longer TTP vs. pts with a worse KPS (n=44) (median KPS 100%: 8.7 mo; 90%: 8.6 mo; ≤ 90%: 3.8 mo; p=0.0027). CGA, ADL, and IADL scores, and CIRS-G did not have a significant impact on TTP. In terms of OS, a high KPS (≥ 90%) significantly increased OS (median 100%: 27.5 mo; 90%: 32.1; <90%: 18.4 mo; p=0.0034). IADL score 8 and CIRS-G 0-3 also correlated with longer OS vs. IADL score <8 (24.1 vs. 17.8 mo, p=0.0061) and CIRS-G >3 (median 0-1: 30.0 mo; 2-3: 32.1 mo; >3: 17.8 mo; p<0.0001). A high KPS increased TTF significantly (median 100%: 5.8.mo; 90%: 4.6 mo, ≤ 90%: 3.0 mo; p=0.0076). Pts with IADL score <8 had a longer TTP (13.7 vs 2.6 mo, p=0.0272), OS (22.7 vs. 4.0 mo, p=0.0031) and TTF (4.6 vs. 2.5 mo, p=0.0043) in the PLD vs. CAP arm. Conclusions: KPS was the most striking predictive factor in this analysis with respect to correlation to TTF and OS. Pts with IADL score <8 treated with PLD had better outcome than pts in CAP arm. Incorporation of CGA into a phase III trial is feasible and yields valuable information for deciding best therapy for MBC patients. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Essex Pharma Essex Pharma, Schering-Plough Essex Pharma, Schering-Plough Schering-Plough, University Hospital Hamburg-Eppendorf Schering-Plough

Abstract Background: PELICAN is a phase III trial of pegylated liposomal doxorubicin (PLD) vs capecitabine (CAP) as first-line therapy of patients (pts) with MBC. In the elderly pts, a CGA and analyses on biologic parameters on inflammation and nutrition, incorporated in the Prognostic Inflammatory and Nutritional Index (PINI) and Glasgow Prognostic Scale (GPS), were performed and results correlated to time to progression (TTP), overall survival (OS), time to treatment failure (TTF), and toxicity. Methods: CGA comprised data on activities of daily living (ADL), instrumental activities of daily living (IADL), ECOG and Karnofsky performance score (KPS), comorbidity (CIRS-G), and comedication. According to CGA, pts were classified into groups 1-3, ranging from fit to frail (Balducci 2000). For biologic assessment, blood samples of 86 pts were collected and centrally analysed. PINI was defined as [(CRP (mg/L) x A1GP (mg/L)]/[albumin (g/L) x prealbumin (mg/L)]. For GPS: pts were allocated a score of 2 if CRP >10mg/L and albumin <35g/L; a score of 1 if one parameter abnormal; and score of 0 if no abnormal values. Results: 210 pts (PLD:105; CAP:105) were randomized, stratified by age & prior anthracycline. Median age was 62y (22-85). Pts received a median of 5 cycles each of PLD and CAP. Median TTP was comparable in both arms (6.7mo PLD vs 7.1mo CAP, p=0.346). There was an insignificant trend for higher GPS and PINI in pts ≥65y. According to CGA, 102 pts were considered fit (group 1, 72%), 21 compromised (group 2, 15%), and 19 frail (group 3, 13%). CGA did not correlate with therapy efficacy. Pts with good KPS of ≥90% (n=46) had a significantly longer TTP vs pts with a worse KPS (n=44) (median KPS 100%: 8.7mo; 90%: 8.6mo; ≥90%: 3.8mo; p=0.0027). Pts with GPS of 0 or 1 had a significantly longer TTP and TTF vs pts with a GPS of 2 (median TTP score 0: 8.3mo, score 1: 9.2mo, score 2: 2.8mo, p=0.0002). Grouping of pts by PINI values (<1; 1-10; >10) showed no correlation with TTP or TTF, and a nonsignificant trend for shorter OS for pts with PINI >10 (p=0.056). Among the analyzed laboratory parameters as single values, CRP showed a significant correlation with TTP (median TTP ≥5mg/L: 10.4mo, > 5 mg/l: 6.2mo, p=0.031) as did serum amyloid A (SAA, median TTP ≥6.8mg/L: 10.4mo, >6.8mg/L: 6.0mo, p=0.026) and serum albumin (median TTP ≥35g/L: 8.3mo, <35g/L: 2.8mo, p=0.009). No significant differences were observed with regard to frequency of AEs or AE-related if stratified according to GPS or PINI. Neither PINI nor GPS correlated with occurrence of overall toxicity grade 3-5; GPS correlated significantly with occurrence of constitutional symptoms (p=0.019). Conclusions: First-line chemotherapy of MBC pts using PLD or CAP showed similar efficacy with respect to TTP. Incorporation of CGA into a phase III trial is feasible and yields information that would otherwise have been missed. Prospective analyses of parameters of systemic inflammation and nutrition may have prognostic significance regarding TTP, TTF, and potentially OS in pts with breast cancer. Results of CGA, PINI and GPS need to be validated prospectively in treatment algorithms for this population. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-11-06.

The incidence of AML increases with age. More than half of the patients (pts) are over 60 years (y) at time of diagnosis. On the other hand, elderly pts are clearly under-represented in the literature. The AML 97 study was designed to register all pts aged 60 and more with newly diagnosed AML. Subsequently, pts were allocated to one of the 3 parts of protocol dependent on Karnofsky's index (KI).

Outcome of elderly patients with AML is usually poor. Increased incidence of high risk AML and intolerance against dose escalation are the main causes for treatment failure. Pharmacokinetic measurements indicated that intracellular Ara-CTP formation is saturated at much lower infusion rates than used in high dose AraC schedules, probably causing AraC accumulation in the plasma and increased toxicity. Therefore, the East German Study Group (OSHO) used intermediate doses of AraC delivered at the presumptive saturating infusion rate over a prolonged period of time. The same schedule was applied to younger (≤60 years of age, AML 96) and older (>60 years of age, AML 97) patients with AML. In the present evaluation, determining factors for complete remission rate and hematopoietic reconstitution were identified.

Treatment of elderly patients (pts) with AML requires a sensitive balance between efficacy and toxicity. In the AML97 study all pts with AML > 60 years (y) were registered and, according to their clinical status, treated in curative, palliative or supportive intention. From a total of 520 pts enrolled, 375 (72%) pts were allocated to the curative, 112 (22%) to the palliative and 33 (6%) to the supportive part of the protocol. Patient characteristics between the 3 groups differed in respect to age, but not in regard to the distribution de novo and secondary AML. Median age of the pts was 66 y (range 60–80 y), 75 y (range 64–90 y) and 76 y (range 63–97 y) for the curative, palliative and supportive protocol respectively. Curative treatment consisted of one (in case of PR after the first chemotherapy of two) courses of induction therapy (AraC 2 g/m2 iv on day (d) 1,3,5,7 in combination with mitoxantrone 10 mg/m2 iv d 1-3) followed by two consolidation courses (AraC 240 mg/m2 iv d 1-5 combined with mitoxantrone 10 mg/m2 iv d 1-2). Palliative treatment included idarubicin 10 mg po d 1 in combination with thioguanine 40 mg po d 1-5, or AraC 80 mg sc d 1-5 or etoposide 100mg po d 1-5. In the supportive arm transfusions were applied. CR was obtained in 75% (95 CI: 68–82%) of pts with de novo AML and in 61% (95 CI: 50–70%) of pts with secondary AML in the curative arm with an early death rate of 12 % (95CI: 7–17%) and 19% (95 CI: 12–24%) respectively. Cytogenetic risk factors at diagnosis were the most important prognostic factor for CR (p<0,0005, multivariate analysis). Pts with favourable karyotype achieved CR in 93%, with normal in 80 %, with other aberrations in 79% and with unfavourable karyotype in 46%. The overall survival (OS) after 2 years in the curative part of protocol was 0,31 ± 0,03 for all pts. With a median follow up of 283 d (range 33 – 1688) the actual OS was 0,58 ± 0,15, 0,38 ± 0,06, 0,39 ± 0,09 and 0,14 ± 0,05 for pts with favourable, normal, other and unfavourable cytogenetics respectively. Interestingly age was not an important determinant, even if results were analysed in a cohort of 603 pts with AML of any age with a similar induction therapy. CR rates of pts below and above 60 y were identical, if they were stratified by cytogenetic risk factors. Median survival was 54 d and only 12 d for pts treated with palliative chemotherapy and supportive therapy respectively. We conclude, that the curative protocol is able to induce high CR in pts with AML > 60 y with low mortality and CR are not different to those of pts < 60 y, if cytogenetics are taking into account. Despite high CR rate, OS remains low and consolidation therapy need to be improved. Transplant protocols with reduced intensity conditioning are currently tested in these patients. Treatment results in the palliative arm are disappointing and confirm the need to develop novel therapeutic strategies.

Objectives: Hematopoietic growth factors are essential in accelerating myeloid reconstitution and reducing treatment morbidity of hematological and non-hematological malignant diseases. In order to understand in more detail the effect of G-CSF on myeloid regeneration, patients (pts) with AML (excluding APL) enrolled in the OSHO AML96 and AML97 trials were analyzed with respect to cytogenetic risk factor, G-CSF treatment and myeloid recovery.

Increasing interest in the treatment of elderly patients or patients with poor performance status (PS) with non-small cell lung cancer (NSCLC) has led to a number of subgroup analyses of clinical trials, and even more importantly, the conduction of trials specifically designed for this cohort. These studies allow some important conclusions. Data from retrospective studies and meta-analyses indicate that the use of platinum-based two-drug combinations in selected,fit elderly patients may produce response rates, survival,and toxicity comparable to those in younger patients. This excludes a per se inferior effectiveness of chemotherapy in the population of elderly patients with NSCLC. A number of more recently introduced agents with a favourable toxicity profile have significantly increased treatment options. Single-agent therapy with vinorelbine, when compared to best supportive care, has been shown to give a statistically significant survival benefit and improve quality of life. Conflicting data from phase II/III trials in elderly patients with NSCLC exist regarding a potential benefit of combination chemotherapy over single-agent treatment in the total cohort of elderly patients, including those with comorbidities or declining functional reserve. A review of the most important trials, assessing treatment options in elderly patients with lung cancer, either prospectively or retrospectively, is provided, and still unresolved issues are addressed.

There is much uncertainty whether chemotherapy is beneficial for elderly patients with advanced lung cancer. Whereas age alone is not an adverse prognostic factor, decline of physiological function and comorbidity can result in higher rates of treatment-related toxicity, in particular myelosuppression. The higher incidence of comorbid conditions, frequently sharing the risk profile of the malignancy, can translate into worse survival. Therefore, a geriatric assessment of the patient's overall situation should guide decision-making. Mainstay of treatment of small cell lung cancer (SCLC), also in the elderly, is combination therapy. Several retrospective analyses reveal that in elderly patients often lower drug doses are delivered. However, the treatment outcome of these patients does not appear to be worse compared to younger patients. For functionally independent elderly patients, combination chemotherapy with carboplatin and etoposide, supported by optimized supportive care, possibly including hematopoietic growth factors (G-CSF) to minimize toxicity, should be considered. Special attention to renal function should be given and individualized drug dosing, adapted to the glomerular filtration rate, is mandatory. For patients with some functional dependence or showing a certain degree of comorbidity, preliminary data indicate that single-agent therapy with carboplatin can confer the same benefit as combination chemotherapy, but with reduced toxicity. Single agent oral etoposide, however, seems to be inferior to combination treatment and should not be given routinely in the treatment of this cohort. Further evaluation of these topics is needed, and can be achieved by trials specifically designed for elderly patients or patients with reduced performance status.

The proportion of older cancer patients is increasing due to demographic and disease-specific reasons. However, this group of patients is severely underrepresented in research and clinical therapy. Limitation in physical and functional capacity with considerable interindividual heterogeneity remains one of the important problems in the treatment decision process. One approach to this problem is the use of a Comprehensive Geriatric Assessment (CGA) to describe and classify these deficits with high validity and reliability. The different domains of CGA are described with special respect to the instruments applied, as CGA has also a key role in the decision process.