Integrating accompanying patients into clinical oncology teams: limiting and facilitating factors.

OBJECTIVES: Since 2018, four establishments in Quebec have been instrumental in implementing the PAROLE-Onco program, which introduced accompanying patients (APs) into healthcare teams to improve cancer patients' experience. APs are patient advisors who have acquired specific experiential knowledge related to living with cancer, using services, and interacting with healthcare professionals. They are therefore in a unique and reliable position to be able to provide emotional, informational, cognitive and navigational support to patients who are dealing with cancer. We aimed to explore APs' perspectives regarding the limiting and facilitating factors in terms of how they are integrated into the clinical oncology teams. METHODS: A qualitative study based on semi-structured interviews and focus groups was conducted with 20 APs at the beginning of their intervention (T1) and, two years later, during a second data collection (T2). Limiting and facilitating factors of APs' integration into clinical teams were analyzed in terms of governance, culture, resources and tools. RESULTS: The limited factors raised by APs to be integrated into clinical teams include the following: confusion about the specific roles played by APs, lifting the egos of certain professionals who feel they are already doing what APs typically do, lack of identification of patient needs, absence of APs in project governance organizational boundaries, and team members' availability. Various communication challenges were also raised, resulting in the program being inadequately promoted among patients. Also mentioned as limiting factors were the lack of time, space and compensation. Creating opportunities for team members to meet with APs, building trust and teaching team members how APs' activities complement theirs were enhancing factors. Other facilitators include APs being involved in decision-making committees, being leaders in promoting the PAROLE-Onco program to patients and clinical team members and creating opportunities to communicate with team members to help enhance their work and provide feedback to improve patient services. Awareness of APs' added value for the team and patients is also a key facilitator. Regarding tools, offering accompanying services by telephone allows both patients and APs to benefit from the flexibility they need. CONCLUSION: Over time, APs were able to identify optimal factors for successful implementation. Recommendations include APs and professionals working in co-construction on organization, leadership, resources and status factors. This could help catalyze a change in culture within health establishments and allow people dealing with cancer to benefit from the experiential knowledge of other patients within their clinical team.

An exploratory cross-sectional study of the effects of ongoing relationships with accompanying patients on cancer care experience, self-efficacy, and psychological distress.

BACKGROUND: Centre hospitalier de l'Université de Montréal in Canada introduced accompanying patients (APs) into the breast cancer care trajectory. APs are patients who have been treated for breast cancer and have been integrated into the clinical team to expand the services offered to people affected by cancer. This study describes the profiles of the people who received the support and explores whether one-offs vs ongoing encounters with APs influence their experience of care, on self-efficacy in coping with cancer, and on their level of psychological distress. METHODS: An exploratory cross-sectional study was carried out among patients to compare patients who had one encounter with an AP (G1) with those who had had several encounters (G2). Five questionnaires were administered on socio-demographic characteristics, care pathway, evaluation of the support experience, self-efficacy in coping with cancer, and level of psychological distress. Logbooks, completed by the APs, determined the number of encounters. Linear regression models were used to evaluate the associations between the number of encounters, patient characteristics, care pathway, number of topics discussed, self-efficacy measures in coping with cancer, and level of psychological distress. RESULTS: Between April 2020 and December 2021, 60% of 535 patients who were offered support from an AP accepted. Of these, one hundred and twenty-four patients participated in the study. The study aimed to recruit a minimum of 70 patients with the expectation of obtaining at least 50 participants, assuming a response rate of 70%. There were no differences between G1 and G2 in terms of sociodemographic data and care pathways. Statistical differences were found between G1 and G2 for impacts on and the return to daily life (p = 0.000), the return to the work and impacts on professional life (p = 0.044), announcement of a diagnosis to family and friends (p = 0.033), and strategies for living with treatment under the best conditions (p = 0.000). Significant differences were found on the topics of cancer (p = 0.000), genetic testing (p = 0.023), therapeutic options (p = 0.000), fatigue following treatment (p = 0.005), pain and discomfort after treatment or surgery (p = 0.000), potential emotions and their management (p = 0.000) and the decision-making processes (p = 0.011). A significant relationship was found between the two groups for patients' ability to cope with cancer (p = 0.038), and their level of psychological distress at different stages of the care pathway (p = 0.024). CONCLUSIONS: This study shows differences between one-time and ongoing support for cancer patients. It highlights the potential for APs to help patients develop self-efficacy and cope with the challenges of cancer treatment.

Accompanying patients in clinical oncology teams: Reported activities and perceived effects.

INTRODUCTION: Since 2018, four establishments in Quebec, Canada, have decided to implement the PAROLE-Onco programme, which introduced accompanying patients (APs) in healthcare teams to improve the experience of cancer patients. APs are patient advisors who have had a cancer treatment experience and who conduct consultations to complement the service offered by providing emotional, informational and educational support to patients undergoing treatments (e.g., radiotherapy, chemotherapy, surgery), mostly for breast cancer. We aimed to explore the evolution of APs' perspectives regarding their activities within the clinical oncology teams as well as the perceived effects of their intervention with patients, the clinical team and themselves. METHODS: A qualitative study based on semistructured interviews and focus groups was conducted with APs at the beginning of their intervention (T1) and 2 years afterwards (T2). The themes discussed were APs' activities and the perceived effects of their interventions on themselves, on the patients and on the clinical team. RESULTS: In total, 20 APs were interviewed. In T2, APs' activities shifted from listening and sharing experiences to empowering patients by helping them become partners in their care and felt generally more integrated into the clinical team. APs help patients feel understood and supported, alleviate stress and become partners in the care they receive. They also alleviate the clinical team's workload by offering a complementary service through emotional support, which, according to them, helps patients feel calmer and more prepared for their appointments with healthcare professionals. They communicate additional information about their patients' health journey, which makes the appointment more efficient for healthcare professionals. When APs accompany patients, they feel as if they can make a difference in patients' lives. Their activities are perceived by some as an opportunity to give back but also as a way of giving meaning to their own experience, in turn serving as a learning experience. CONCLUSION: By mobilizing their experiential knowledge, APs provide emotional, informational, cognitive and navigational support, which allows patients to be more empowered in their care and which complements professionals' scientific knowledge, thereby helping to refine their sensitivity to the patients' experiences. PATIENT OR PUBLIC CONTRIBUTION: Two patient-researchers have contributed to the study design, the conduct of the study, the data analysis and interpretation, as well as in the preparation and writing of this manuscript.

Changing Landscape of Radiation Therapy for Advanced Cervical Cancer With a Focus on Interstitial Brachytherapy: A Canadian Practice Patterns Survey.

PURPOSE: To document the evolution of radical radiation therapy and interstitial brachytherapy (ISBT) utilization practice patterns across Canada, including use of imaging, technical details, and usage of anesthesia/analgesia, and to compare advanced (AC) versus nonadvanced (nAC) brachytherapy (BT) center practices. METHODS AND MATERIALS: All Canadian centers with BT services were identified. One gynecology radiation oncologist per center was sent a 64-item questionnaire regarding the center's practice for patients with cervical cancer. Centers were categorized based on availability of advanced BT expertise (AC) versus those referring patients to other centers for advanced BT techniques (nAC). Aggregate responses are reported and compared with practice patterns identified in our previous survey. Descriptive statistics were used to summarize data, and the Fisher exact test, Fisher-Freeman-Halton, or Mann-Whitney-Wilcox test was used for comparisons. RESULTS: Thirty-seven of 38 respondents completed the survey (response rate: 97.4%). Compared with 2015, there has been an increase in utilization of magnetic resonance imaging as the sole imaging modality for BT planning: 3 of 26 (11%) versus 12 of 37 (32%; P = .03). The number of centers with the ability to perform ISBT increased in 2020 compared with 2015 (26/37 [70%] vs 13/26 [50%], P = .710); this trend is likely due to an increase in use of hybrid (Vienna, Utrecht, Venezia) applicators (36% [2015] vs 84% [2020]; P = .175). Fifteen (40%) centers had the ability to perform perineal-ISBT (P-ISBT). Sixteen and 21 centers were identified as AC and nAC, respectively. All 16 AC centers had the ability to perform ISBT, compared with only 10 nAC centers (P < .001). A higher proportion of AC centers had fellowship-trained radiation oncologists performing brachytherapy, compared with nAC centers (94% vs 14%, P < .001). In terms of anesthesia, conscious sedation was the only available choice at low-patient-volume centers (8/37, 21%) performing intracavitary BT only. Those performing ISBT had choice of general, spinal, and epidural anesthesia. CONCLUSIONS: In Canada, high-quality, modern management radiation therapy practices are consistently offered to patients with cervical cancer. There is a trend toward increased utilization of ISBT. Accumulation of evidence toward the use of ISBT, increased utilization of high-quality imaging modalities such as magnetic resonance imaging, and availability of hybrid applicators are potential contributors for this upward trend.

Quality of Life: A Prospective Randomized Trial of Palliative Volumetric Arc Therapy Versus 3-Dimensional Conventional Radiation Therapy.

PURPOSE: Volumetric arc therapy (VMAT) is a radiation therapy (RT) technique that spares normal tissues from high and intermediate RT doses but increases the volume of tissues receiving low doses of RT compared with 3-dimensional conformal RT (3DCRT). We hypothesized that palliative VMAT would reduce the detriment to patient quality of life (QOL) compared with palliative 3DCRT. METHODS AND MATERIALS: This phase 2 trial randomized patients to palliative RT using VMAT or 3DCRT to 1 painful site of metastatic disease in the trunk. Treating physicians could choose 8 Gy in 1 fraction or 20 Gy in 5 fractions to stratify randomization. The primary endpoint was the change in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Version 3.0 (EORTC QLQ-C30) global health status QOL subscale at 1 week after RT. Repeated measures analysis of variance was used to assess the relationship of patient QOL over time with other factors. RESULTS: From July 2014 to November 2017, 37 patients who underwent 3DCRT and 32 patients who underwent VMAT were randomized into the study. Median overall survival was 9 months. Overall pain responses to RT were equivalent (P = .53) between the techniques. Patient compliance in returning QOL questionnaires was 94%, 81%, and 69% at baseline, 1 week after RT, and 1 month after RT, respectively. At 1 week after RT, change in global QOL was not significantly (P = .31) different between VMAT versus 3DCRT. At 4 weeks after RT, VMAT induced significantly (P = .049) less global QOL deterioration than 3DCRT did. Patients who underwent VMAT maintained better physical (P = .012), role (P = .041), and social (P = .025) functioning, but they reported more diarrhea symptoms (P = .017) than in the 3DCRT group. CONCLUSIONS: Palliative VMAT and 3DCRT did not differ in their ability to control pain; however, palliative VMAT induced fewer QOL detriments than 3DCRT did at 4 weeks after RT.

Vienna-II ring applicator for distal parametrial/pelvic wall disease in cervical cancer brachytherapy: An experience from two institutions: Clinical feasibility and outcome.

PURPOSE: Recent evidence from EMBRACE shows that around 16% patients with locally advanced cervical cancer (LACC) have residual tumor in distal parametrium (DP) and pelvic wall disease (LPW) after concurrent radio-chemotherapy (CCRT). Adequate target coverage with standard brachytherapy approaches represents a challenge. Therefore, we modified the Vienna I applicator with an add-on cap allowing for additional oblique needles into the DP/LPW (Vienna II). We report here the feasibility and clinical outcomes using Vienna II applicator in LACC patients treated in 2 institutions. METHODS AND MATERIALS: 69 patients with residual disease in DP/LPW after CCRT were accrued. FIGO (2009) stage was 26% IIB, 52% III, 15% IVA, 7% IVB (para-aortic nodes). At diagnosis 91% had disease involving DP/LPW. After CCRT, patients underwent image guided adaptive brachytherapy (IGABT) using Vienna II applicator. IGABT details, acute complications, dose volume parameters and clinical outcome variables were compiled and analyzed. RESULTS: Residual DP/LPW disease at BT was found in 90% patients. Median total number of needles were 7 [3-15], oblique 4 [1-7]. Manageable intraoperative utero-vaginal complications occurred in 8 patients and manageable arterial bleeding in 6 patients during removal. Mean distance between tandem and outer contour of CTVHR was 38 mm and mean CTVHR (±SD) volume was 69 ±â€¯32 cm3. The mean D90 CTVHR was 86 ±â€¯7 Gy (EQD2) and mean (±SD) D2cm3 (Gy, EQD2) 86 ±â€¯12, 68 ±â€¯7, 68 ±â€¯9 for bladder, rectum and sigmoid respectively. Actuarial LC, PFS, OS at 3/5 years was 76/72%, 56/50%, 62/54% and G3-4 late toxicities (n = 23) were observed in 14 patients (20%). CONCLUSIONS: IGABT using Vienna II applicator allows for appropriate target coverage in tumors extending into DP/LPW at the time of BT. Clinical use is feasible and results in good local control, DFS and OS with moderate rate of acute and late ≥G3 toxicity.

MRI-based interstitial brachytherapy for vaginal tumors: A multi-institutional study on practice patterns, contouring, and consensus definitions of target volumes.

PURPOSE: Interstitial brachytherapy (ISBT) can be effective for vaginal tumors due to its ability to deliver conformal treatment with 3D planning. As there is no consensus for 3D vaginal brachytherapy (BT) contouring, the goals of this study are to evaluate the variability in practices and contouring, and to develop consensus concepts on target definitions. METHODS: A survey/contouring study was conducted with 16 radiation oncologists from 10 Canadian academic centers. The study included three vaginal ISBT cases. Participants were provided staging, prebrachytherapy (pre-BT), and BT MRIs. Participants responded to a questionnaire and contoured on the provided images. Agreement between contours was analyzed. A meeting was held to develop consensus definitions of targets. RESULTS: Median ISBT experience was 3.5 years. All 16 participants regularly contour with MRI, whereas three also plan on MRI. For the three cases, there was variation into how CTVHR and CTVIR was defined. Kappa statistics showed higher agreement with bulky tumors (mean 0.59) as compared with small residual tumors (mean 0.29). For all cases, kappa was highest in pre-BT GTVres as compared with BT GTVres (mean 0.58, 0.46). Consensus concepts to define targets were developed. CONCLUSIONS: Variations exist in how ISBT targets are defined for vaginal tumors. Highest contouring variability was seen with small residual at BT. Contouring is more consistent on pre-BT MRI as compared with BT MRI suggesting a needle distortion effect. Consensus CTVHR and CTVIR definitions have been developed and further work is warranted to establish international standards.

Nodal failure after chemo-radiation and MRI guided brachytherapy in cervical cancer: Patterns of failure in the EMBRACE study cohort.

PURPOSE/OBJECTIVE(S): To investigate the patterns of nodal failure in patients enrolled in the international multicentre EMBRACE study. MATERIALS/METHODS: Nodal disease at diagnosis (N-, N+) and nodal failure were analysed per region (NF) (pelvic (parametrial, common iliac, internal/external iliac), inguinal and para-aortic (PAO)) in 1338 patients. Treatment consisted of chemo-radiation and MRI guided brachytherapy. PAO radiotherapy and/or nodal boost was left to the treating centre. At time of diagnosis 52% of patients had pathologic nodes. Frequency analyses were performed in relation to patient, primary tumour and nodal disease characteristics, and treatment related factors. RESULTS: Median follow up was 34 months and 83% of NF occurred within 24 months. At diagnosis 99% of the N+ patients had pathologic nodes in the pelvis and 14% in the PAO. NFpelvic and NFPAO were reported in 55% and 68% of patients with NF, respectively. Overall NF was reported in 152 patients (11%); 7 and 16% for N- and N+ patients. Of the patients with NF, 41% were located outside the elective target (39% PAO), 40% inside and 35% inside the nodal boost target. Twelve percent of N+ patients that received a nodal boost had a NF inside the nodal boost target. CONCLUSION: Within the EMBRACE study cohort the overall number of patients developing nodal failure is low, significantly lower for N- compared to N+ patients. Pathological nodes at diagnosis are mainly located in the pelvis, whereas nodal failures are more often reported in the PAO region. About 40% of all nodal failures were reported outside the treatment targets.

The EMBRACE II study: The outcome and prospect of two decades of evolution within the GEC-ESTRO GYN working group and the EMBRACE studies.

The publication of the GEC-ESTRO recommendations one decade ago was a significant step forward for reaching international consensus on adaptive target definition and dose reporting in image guided adaptive brachytherapy (IGABT) in locally advanced cervical cancer. Since then, IGABT has been spreading, particularly in Europe, North America and Asia, and the guidelines have proved their broad acceptance and applicability in clinical practice. However, a unified approach to volume contouring and reporting does not imply a unified administration of treatment, and currently both external beam radiotherapy (EBRT) and IGABT are delivered using a large variety of techniques and prescription/fractionation schedules. With IGABT, local control is excellent in limited and well-responding tumours. The major challenges are currently loco-regional control in advanced tumours, treatment-related morbidity, and distant metastatic disease. Emerging evidence from the RetroEMBRACE and EMBRACE I studies has demonstrated that clinical outcome is related to dose prescription and technique. The next logical step is to demonstrate excellent clinical outcome with the most advanced EBRT and brachytherapy techniques based on an evidence-based prospective dose and volume prescription protocol. The EMBRACE II study is an interventional and observational multicentre study which aims to benchmark a high level of local, nodal and systemic control while limiting morbidity, using state of the art treatment including an advanced target volume selection and contouring protocol for EBRT and brachytherapy, a multi-parametric brachytherapy dose prescription protocol (clinical validation of dose constraints), and use of advanced EBRT (IMRT and IGRT) and brachytherapy (IC/IS) techniques (clinical validation). The study also incorporates translational research including imaging and tissue biomarkers.

Helical Tomotherapy for Postmastectomy Radiotherapy after Immediate Left Breast Reconstruction: A Case Study.

A 43-year-old premenopausal female presented with a multicentric infiltrating lobular carcinoma of the left breast with axillary nodes metastasis. She underwent modified radical mastectomy with axillary lymph node dissection (level I and II) followed by a mixed autologous latissimus dorsi flap reconstruction with the addition of prosthesis. The final pathological analysis revealed a 6 cm invasive lobular carcinoma pT3N2aM0, grade III/III, estrogen and progesterone positive, human epidermal growth factor receptor 2 (HER2) negative, with 5/16 positive lymph nodes. She received neoadjuvant chemotherapy with doxorubicin and cyclophosphamide followed by paclitaxel. Post-mastectomy radiotherapy with axillary, supraclavicular and internal mammary lymph nodes (IMLN) irradiation was delivered to a dose of 50 Gy/25 fx. In this case with multiple risk factors for radiation-induced cardiac toxicity (left-sided lesion, internal mammary lymph nodes (IMLN) irradiation), we discuss the role of helical tomotherapy as a treatment alternative to conventional tangential radiotherapy.

Xerostomia in patients treated for oropharyngeal carcinoma: comparing linear accelerator-based intensity-modulated radiation therapy with helical tomotherapy.

BACKGROUND: In comparison to sliding-window intensity-modulated radiation therapy (sw-IMRT), we hypothesized that helical tomotherapy (HT) would achieve similar locoregional control and, at the same time, decrease the parotid gland dose, thus leading to a xerostomia reduction. METHODS: The association between radiation techniques, mean parotid dose, and xerostomia incidence, was reviewed in 119 patients with advanced oropharyngeal carcinoma treated with concurrent chemoradiation using sw-IMRT (n = 59) or HT (n = 60). RESULTS: Ipsilateral and contralateral parotid mean doses were significantly lower for patients treated with HT versus sw-IMRT: 24 Gy versus 32 Gy ipsilaterally and 20 Gy versus 25 Gy contralaterally. The incidence of grade ≥2 xerostomia was significantly lower in the HT group than in the sw-IMRT group: 12% versus 78% at 6 months, 3% versus 51% at 12 months, and 0% versus 25% at 24 months. Total parotid mean dose <25 Gy was strongly associated to a lower incidence of grade ≥2 xerostomia at 6, 12, and 24 months. CONCLUSION: This retrospective series suggests that using HT can better spare the parotid glands while respecting quantitative analysis of normal tissue effects in the clinic (QUANTEC)'s criteria.

Hemoglobin level in cervical cancer: a surrogate for an infiltrative phenotype.

OBJECTIVE: Hemoglobin (Hb) is a prognostic factor in cervical cancer, but the underlying mechanisms remain unknown. In this study, we hypothesized that low Hb level, either before or during radiotherapy (RT), is a surrogate for a more infiltrative and therefore aggressive disease, with uterine corpus invasion and nodal metastases. METHODS AND MATERIALS: Prospectively collected data of patients with locally advanced cervical cancer treated with curative intent using chemoradiation at a tertiary academic center was reviewed. All eligible patients had a positron emission tomographic scan and pelvic magnetic resonance imaging. Hemoglobin levels before RT and Hb nadir during RT were collected from the medical record. RESULTS: The median follow-up for 263 eligible patients was 38.7 months. Ninety-six patients (36.5%) had both uterine corpus invasion and positron emission tomography-positive nodal disease (C+N+). Patients with pretreatment Hb level of less than 120 g/L were more likely to have C+N+ disease (47%) compared with patients with a high pretreatment Hb level (32%; P = 0.034). The 3-year disease-free survival and overall survival (OS) were significantly lower in the C+N+ group compared with the remaining patients (40.1% vs 76.1%, P < 0.001, and 59.7% vs 83.1%, P < 0.001, respectively). Patients with low Hb nadir were more likely to have a C+N+ disease (P < 0.001), and low Hb nadir during RT was significantly an indicator of a higher recurrence rate (P = 0.002) and lower OS (P < 0.001). In multifactor analysis, statistically significant prognostic factors for OS included histology, high-echelon nodal involvement, tumor volume on magnetic resonance imaging, C+N+ status, and Hb nadir during treatment. Pretreatment Hb level was not an independent prognostic factor. CONCLUSIONS: The combination of corpus invasion and nodal metastases is associated with lower Hb level and inferior prognosis. Because C+N+ state is related to tumor growth from early invasion to the time of presentation, it is unlikely that the correction of Hb level during treatment will have a major impact on outcome.

A Monte Carlo based formalism to identify potential locations at high risk of tumor recurrence with a numerical model for glioblastoma multiforme.

PURPOSE: The strategy currently used to treat glioblastoma multiforme (GBM) patients, which mostly relies on population-based failure patterns, does not consider the important variability in such patterns reported in the literature. As part of the multidisciplinary efforts being made to develop personalized therapeutic approaches, numerical models of tumor growth and treatment are increasingly being used by different groups around the world. In this study, a new formalism relying on the proliferation-invasion model is developed to identify potential locations of GBM recurrences. The authors assess the sensitivity of the location of potential tumor recurrences to the input parameter values predicted for a given patient by varying those values using a Monte-Carlo based approach. Our approach is designed to be prospective in the sense that it relies on patient-specific imaging data that can be gathered in one single preradiotherapy imaging session. METHODS: The authors modeled the infiltration paths of glial cells using patient-specific diffusion tensor imaging (DTI) data. Nine GBM patients with preradiotherapy DTI data are considered in this study. The possible locations of tumor recurrences are determined by randomly selecting many ensembles of values for each of the growth and radiobiological parameters in the GBM growth model. A novel concept, the occurrence probability (OP), is introduced to assess the sensitivity of potential tumor recurrence locations to the input parameter values. For a given patient, the OP map is derived from a superposition of all potential tumor recurrence locations obtained with all sets of parameter values. RESULTS: For eight out of nine of patients, the authors have identified a statistically significant region where the OP is above 50%. For two patients, these high risk regions are found to be located at a distance greater than 3.9 cm from the border of the gross tumor volume highlighting the inaccuracy of current margins for some patients. The exact location and size of these volumes with OP > 50 % are, however, sensitive to the number N of ensembles of parameter values for N ≲ 400. On the other hand, the authors have identified for each patient a threshold OP, the OP(T), which defines a volume that converges more rapidly with increasing N. The OP(T) for each patient varies between 20% and 40%. The volume defined by OP > OP(T) may be an adequate candidate to define a personalized margin for radiotherapy treatment planning of GBM patients. CONCLUSIONS: A new Monte-Carlo based formalism was described and used to assess the variability of sites of potential recurrence predicted by the proliferation-invasion model to input parameter values. The authors have shown that high risk areas could be consistently identified with a limited number of sets (N ≲ 400) of randomly chosen parameter values. A major strength of this formalism is its potential prospective nature. Although a validation of the accuracy of the model-predicted tumor recurrence location still remains to be done, our method is potentially applicable to orient patient-specific definition of margins.

The Saccharomyces cerevisiae Piccolo NuA4 histone acetyltransferase complex requires the Enhancer of Polycomb A domain and chromodomain to acetylate nucleosomes.

Chromatin modification complexes are key gene regulatory factors which posttranslationally modify the histone component of chromatin with epigenetic marks. To address what features of chromatin modification complexes are responsible for the specific recognition of nucleosomes compared to naked histones, we have performed a functional dissection of the Esa1-containing Saccharomyces cerevisiae Piccolo NuA4 histone acetyltransferase complex. Our studies define the Piccolo determinants sufficient to assemble its three subunits into a complex as well as Piccolo determinants sufficient to specifically acetylate a chromatin template. We find that the conserved Enhancer of Polycomb A (EPcA) homology region of the Epl1 component and the N-terminal 165 amino acids of the Yng2 component of Piccolo are sufficient with Esa1 to specifically act on nucleosomes. We also find that the Esa1 chromodomain plays a critical role in Piccolo's ability to distinguish between histones and nucleosomes. In particular, specific point mutations in the chromodomain putative hydrophobic cage which strongly hinder growth in yeast greatly reduce histone acetyltransferase activity on nucleosome substrates, independent of histone methylation or other modifications. However, the chromodomain is not required for Piccolo to bind to nucleosomes, suggesting a role for the chromodomain in a catalysis step after nucleosome binding.