PEACE V - Salvage Treatment of OligoRecurrent nodal prostate cancer Metastases (STORM): a study protocol for a randomized controlled phase II trial.

BACKGROUND: Pelvic nodal recurrences are being increasingly diagnosed with the introduction of new molecular imaging techniques, like choline and PSMA PET-CT, in the restaging of recurrent prostate cancer (PCa). At this moment, there are no specific treatment recommendations for patients with limited nodal recurrences and different locoregional treatment approaches are currently being used, mostly by means of metastasis-directed therapies (MDT): salvage lymph node dissection (sLND) or stereotactic body radiotherapy (SBRT). Since the majority of patients treated with MDT relapse within 2 years in adjacent lymph node regions, with an estimated median time to progression of 12-18 months, combining MDT with whole pelvic radiotherapy (WPRT) may improve oncological outcomes in these patients. The aim of this prospective multicentre randomized controlled phase II trial is to assess the impact of the addition of WPRT to MDT and short-term androgen deprivation therapy (ADT) on metastasis-free survival (MFS) in the setting of oligorecurrent pelvic nodal recurrence. METHODS & DESIGN: Patients diagnosed with PET-detected pelvic nodal oligorecurrence (≤5 nodes) following radical local treatment for PCa, will be randomized in a 1:1 ratio between arm A: MDT and 6 months of ADT, or arm B: WPRT added to MDT and 6 months of ADT. Patients will be stratified by type of PET-tracer (choline, FACBC or PSMA) and by type of MDT (sLND or SBRT). The primary endpoint is MFS and the secondary endpoints include clinical and biochemical progression-free survival (PFS), prostate cancer specific survival, quality of life (QoL), toxicity and time to castration-resistant prostate cancer (CRPC) and to palliative ADT. Estimated study completion: December 31, 2023. DISCUSSION: This is the first prospective multicentre randomized phase II trial assessing the potential of combined WPRT and MDT as compared to MDT alone on MFS for patients with nodal oligorecurrent PCa. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03569241, registered June 14, 2018, ; Identifier on Swiss National Clinical Trials Portal (SNCTP): SNCTP000002947, registered June 14, 2018.

Prediction of local and metastatic recurrence in solitary fibrous tumor: construction of a risk calculator in a multicenter cohort from the French Sarcoma Group (FSG) database.

BACKGROUND: Solitary fibrous tumors (SFT) are rare unusual ubiquitous soft tissue tumors that are presumed to be of fibroblastic differentiation. At present, the challenge is to establish accurate prognostic factors. PATIENTS AND METHODS: A total of 214 consecutive patients with SFT diagnosed in 24 participating cancer centers were entered into the European database (www.conticabase.org) to perform univariate and multivariate analysis for overall survival (OS), local recurrence incidence (LRI) and metastatic recurrence incidence (MRI) by taking competing risks into account. A prognostic model was constructed for LRI and MRI. Internal and external validations of the prognostic models were carried out. An individual risk calculator was carried out to quantify the risk of both local and metastatic recurrence. RESULTS: We restricted our analysis to 162 patients with local disease. Twenty patients (12.3%) were deceased at the time of analysis and the median OS was not reached. The LRI rates at 10 and 20 years were 19.2% and 38.6%, respectively. The MRI rates at 10 and 20 years were 31.4% and 49.8%, respectively. Multivariate analysis retained age and mitotic count tended to significance for predicting OS. The factors influencing LRI were viscera localization, radiotherapy and age. Mitotic count, tumor localization other than limb and age had independent values for MRI. Three prognostic groups for OS were defined based on the number of unfavorable prognostic factors and calculations were carried out to predict the risk of local and metastatic recurrence for individual patients. CONCLUSION: LRI and MRI rates increased between 10 and 20 years so relapses were delayed, suggesting that long-term monitoring is useful. This study also shows that different prognostic SFT sub-groups could benefit from different therapeutic strategies and that use of a survival calculator could become standard practice in SFTs to individualize treatment based on the clinical situation.

[Prostate cancer and androgen deprivation: benefits of psychological counseling]. / Cancer de la prostate et déprivation androgénique: bénéfices d'un accompagnement psychologique.

Androgen deprivation is a therapeutic option for patients with prostate cancer, however with a range of side effects that negatively affects their physical and psychological condition. A multidisciplinary care program, ADAPP ("Androgenic deprivation in prostate cancer patients"), has been created with a special focus on managing these side effects. This article describes the intervention of the liaison psychiatry within this program, with care options ranging from psychological support to intensive psychotherapy to address patients' intrapsychic dynamics throughout this care program. Clinical cases are reported to illustrate the relevance and the necessity of this specialized counselling.

[Relationship between doses to anatomical structures and erectile dysfunction after radiotherapy for prostate cancer: A systematic review]. / Relations entre doses dans les structures anatomiques et dysfonction érectile après radiothérapie pour un cancer de la prostate : revue systématique de la littérature.

PURPOSE: During prostatic radiotherapy, damage to several anatomical structures could be the cause of erectile dysfunction: corpora cavernosa, internal pudendal arteries, penile bulb, and neurovascular bundles. Numerous studies have analysed the correlations between the dose received by these structures and erectile function. The objective of this article is to make a systematic review on current knowledge. MATERIALS AND METHODS: A systematic review was performed in the Medline database using the search engine PubMed. Keywords for the search included: erectile dysfunction, penile bulb, corpora cavernosa, cavernosum, neurovascular bundles, radiation therapy, cancer, prostate cancer. The selected articles must study a correlation between erectile dysfunction and the dose received by anatomical structures. A total of 152 articles were identified. Of these 152 articles, 45 fulfilled the defined selection criteria. RESULTS: For corpora cavernosa, seven studies were identified, only two studies demonstrated a significant correlation between the dose received by corpora cavernosa and the occurrence of erectile dysfunction. For penile bulb, only 15 of 23 studies showed a correlation. A mean dose on the penile bulb greater than 20Gy was found to be predictive of erectile dysfunction. None of the eight trials concerning neurovascular bundles succeeded to show a correlation between dose and erectile dysfunction. Only one study evaluated the relationship between the dose received by internal pudendal arteries and erectile dysfunction but was found to be negative. However, vessels-sparing studies showed good results on erectile function preservation without compromising the target volume. CONCLUSION: We currently have little data to show a correlation between erectile dysfunction and sexual structures. It would be necessary to have additional prospective studies evaluating the impact of an optimization on these sexual structures on erectile dysfunction.

Ultrahypofractionated Radiotherapy for Localised Prostate Cancer: How Far Can We Go?

Following adoption of moderately hypofractionated radiotherapy as a standard for localised prostate cancer, ultrahypofractioned radiotherapy delivered in five to seven fractions is rapidly being embraced by clinical practice and international guidelines. However, the question remains: how low can we go? Can radiotherapy for prostate cancer be delivered in fewer than five fractions? The current review summarises the evidence that radiotherapy for localised prostate cancer can be safely and effectively delivered in fewer than five fractions using high dose rate brachytherapy or stereotactic body radiotherapy. We also discuss important lessons learned from the single-fraction high dose rate brachytherapy experience.

Surgical Treatments of Benign Prostatic Hyperplasia and Prostate Cancer Stereotactic Radiotherapy: Impact on Long-Term Genitourinary Toxicity.

AIMS: Although the results on acute and late toxicity of ultrahypofractionation are encouraging, data on safety in prostate cancer patients with a medical history of transurethral resection of the prostate (TURP) or adenomectomy remain scarce, especially in cases of repeated procedures. The aim of the present study was to report on long-term toxicities after stereotactic body radiotherapy (SBRT) of prostate cancer patients with previous surgical treatment of benign prostatic hyperplasia. MATERIALS AND METHODS: Among 150 patients treated with SBRT (median dose 36.25 Gy in five fractions) realised from 2014 to 2019 in a single-centre institution, data of 24 men with a history of TURP (n = 19) or adenomectomy (n = 5) were analysed. Repeated TURP was carried out in three patients, with a median time between surgery and SBRT of 54 months. Genitourinary toxicity was assessed using the Common Terminology Criteria for Adverse Events v4.0 grading scale. RESULTS: With a median follow-up of 45 months, 10 of 24 (42%) patients experienced at least one episode of transient haematuria. One patient (4%) with three previous TURP presented a grade 3 acute non-infective cystitis. Late grade 2 and 3 genitourinary toxicities were observed in eight (33%) and four patients (17%) (two treated with adenomectomy, one with multiple TURP and one with a 140 cm3 prostate size), respectively, with no grade ≥4 adverse events. A complete recovery of grade 3 genitourinary toxicities was observed for all patients after hyperbaric oxygen therapy. CONCLUSION: Prostate SBRT is feasible and well-tolerated in patients with a medical history of surgical treatments of benign hyperplasia. Patients with prior adenomectomy or multiple TURP are at higher risk of developing severe genitourinary toxicity and should be carefully evaluated before SBRT treatments.

Prognostic impact of abdominal adiposity, waist circumference and body mass index in patients with intermediate-risk prostate cancer treated with radiotherapy.

OBJECTIVE: We tested the potential role of abdominal visceral (VAT) and subcutaneous (SAT) adipose tissues, waist circumference (WC) and body mass index (BMI) as prognostic factors in patients with intermediate-risk prostate cancer (clinical stage T1b-2b, and Gleason Score (GS)=7 and prostate-specific antigen PSA level <15 ng ml(-1), or GS ≤ 6 and PSA between 10 and 20 ng ml(-1)) treated with ultrasound-based image-guided radiotherapy. METHODS: VAT, SAT and WC (measured from planning abdominal computed tomography) and BMI were compared with clinical and pathologic factors using univariate analyses. Cox regression analyses were performed to evaluate whether obesity indices significantly predicted biochemical disease free-survival (bDFS). RESULTS: Of the 112 eligible patients, 30 (27%) were obese. Median BMI at baseline was 27.5 kg m(-2) (range, 19.2-51.5 kg m(-2)). Greater abdominal adiposity, WC and BMI were significantly associated with younger age at diagnosis and increased prostate volume (P=0.003 and P=0.002, respectively). No significant correlation between obesity measures and T-stage, GS, PSA or percentage of positive cores at biopsy was found. On Cox regression analyses, none of the obesity measures predicted for bDFS. No association was observed between obesity indices and surrogate markers of biochemical failure as PSA nadir (nPSA) or time to nPSA. CONCLUSIONS: Abdominal adiposity, WC and BMI are associated with younger age at diagnosis and greater prostate volume but not with an increased risk of biochemical failure in patients with intermediate-risk prostate cancer.

Guillain-Barré syndrome as an atypical manifestation of an esophageal carcinoma.

Guillain-Barré syndrome (GBS) is an acute demyelinating polyradiculoneuropathy normally associated with a preceding infection, but sometimes it can be linked to a subjacent malignancy. We report an unusual case of GBS occurring as the first clinical manifestation of an esophageal adenocarcinoma in a 65-year-old patient. A GBS neuropathy of undetermined origin may be associated with an underlying tumor and esophageal cancer has to be considered in the differential diagnosis.

Detection rate, pattern of relapse and influence on therapeutic decision of PSMA PET/CT in patients affected by biochemical recurrence after radical prostatectomy, a retrospective case series.

AIMS: 68Ga-Prostate-specific membrane antigen (PSMA) PET/CT is widely used in patients with biochemical recurrence (BCR) after radical prostatectomy. We collected data about patients staged with PSMA PET/CT after BCR (PSA < 1 ng/ml) in four different institutes. Impact of baseline features (Gleason score, risk classification, PSA at recurrence, PSA doubling time and time to recurrence) was explored to understand predictive factors of (PSMA) PET/CT positivity. Impact of restaging on following treatment approaches was reported. RESULTS: 92 patients were included. PSMA PET/CT detection rate was 56.5% and low-volume disease (≤ 3 non-visceral lesions) was detected in 52.2% of patients. After positive scan, 13.5% of patients still lies on observation, ADT alone was administered in 30.8% of cases, Stereotactic body RT (SBRT) alone was delivered to 44.2% of patients and 11.5% of patients underwent concomitant SBRT and ADT. Seven patients underwent conventional salvage prostate bed RT. Chi-squared test showed a higher rate of positive PSMA PET/CT for patients with Gleason score > 7 (p = 0.004) and TTR < 29.5 months (p = 0.003). CONCLUSIONS: PSMA PET/CT showed a high detection rate. This influenced clinical management in a significant percentage of patients, allowing treatment tailoring on the basis of imaging.

[From bunker construction to patient treatment: quality controls applied to modern radiotherapy techniques]. / De la construction du bunker à la prise en charge du patient : contrôles qualité des techniques modernes de radiothérapie.

Installation and use of a new radiotherapy device require an adequate quality and safety policy. The process leading to the commissioning of an accelerator following the construction of a bunker includes, among other tasks, the installation of the accelerator, the verification of compliance with the specifications, the signature of the acceptance specification as well as the process of characterization and modeling of the accelerator before its clinical use. The emergence of modern radiotherapy techniques, such as intensity modulated conformational radiotherapy and stereotactic radiotherapy, has resulted in more complex quality controls. The purpose of this article is to explain the different stages of the implementation of innovative radiotherapy techniques and to specify their features.

Standard of Care Versus Metastases-directed Therapy for PET-detected Nodal Oligorecurrent Prostate Cancer Following Multimodality Treatment: A Multi-institutional Case-control Study.

BACKGROUND: Most prostate cancer (PCa) patients with a biochemical failure following primary multimodality treatment (surgery and postoperative radiotherapy) relapse in the nodes. OBJECTIVE: To perform a matched-case analysis in men with lymph node recurrent PCa comparing standard of care (SOC) with metastasis-directed therapy (MDT). DESIGN, SETTING, AND PARTICIPANTS: PCa patients with a prostate-specific antigen (PSA) progression following multimodality treatment were included in this retrospective multi-institutional analysis. INTERVENTION: The SOC cohort (n=1816) received immediate or delayed androgen deprivation therapy administered at PSA progression. The MDT cohort (n=263) received either salvage lymph node dissection (n=166) or stereotactic body radiotherapy (n=97) at PSA progression to a positron emission tomography-detected nodal recurrence. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint, cancer-specific survival (CSS), was analyzed using the Kaplan-Meier method, log-rank test, Cox proportional hazards models, and propensity score-matched analyses. RESULTS AND LIMITATIONS: At a median follow-up of 70 (interquartile range: 48-98) mo, MDT was associated with an improved CSS on univariate (p=0.029) and multivariate analysis (hazard ratio: 0.33, 95% confidence interval [CI]: 0.17-0.64) adjusted for the year of radical prostatectomy (RP), age at RP, PSA at RP, time from RP to PSA progression, Gleason score, surgical margin status, pT- and pN-stage. In total, 659 men were matched (3:1 ratio). The 5-yr CSS was 98.6% (95% CI: 94.3-99.6) and 95.7% (95% CI: 93.2-97.3) for MDT and SOC, respectively (p=0.005, log-rank). The main limitations of our study are its retrospective design and lack of standardization of systemic treatment in the SOC cohort. CONCLUSIONS: MDT for nodal oligorecurrent PCa improves CSS as compared with SOC. These retrospective data from a multi-institutional pooled analysis should be considered as hypothesis-generating and inform future randomized trials in this setting. PATIENT SUMMARY: Prostate cancer patients experiencing a lymph node recurrence might benefit from local treatments directed at these lymph nodes.

Early-stage Favourable Anal Cancer: A Retrospective Analysis of Clinical Outcomes of a Moderately Low Dose Elective Nodal Intensity-modulated Radiotherapy Schedule.

In this retrospective study we evaluated the long-term results of 35 early-stage favourable T1-2 N0 M0 anal cancer patients treated with intensity-modulated radiotherapy techniques combining low dose prophylactic inguinal-pelvic irradiation with dose-escalated boost. Optimal locoregional control and good tolerance makes this treatment a valuable alternative to brachytherapy boost and involved-field radiotherapy plans.

Pattern of Progression after Stereotactic Body Radiotherapy for Oligometastatic Prostate Cancer Nodal Recurrences.

AIMS: To report the relapse pattern of stereotactic body radiotherapy (SBRT) for oligorecurrent nodal prostate cancer (PCa). MATERIALS AND METHODS: PCa patients with ≤3 lymph nodes (N1/M1a) at the time of recurrence were treated with SBRT. SBRT was defined as a radiotherapy dose of at least 5 Gy per fraction to a biological effective dose of at least 80 Gy to all metastatic sites. Distant progression-free survival was defined as the time interval between the first day of SBRT and appearance of new metastatic lesions, outside the high-dose region. Relapses after SBRT were recorded and compared with the initially treated site. Secondary end points were local control, time to palliative androgen deprivation therapy and toxicity scored using the Common Terminology Criteria for Adverse Events v4.0. RESULTS: Overall, 89 metastases were treated in 72 patients. The median distant progression-free survival was 21 months (95% confidence interval 16-25 months) with 88% of patients having ≤3 metastases at the time of progression. The median time from first SBRT to the start of palliative androgen deprivation therapy was 44 months (95% confidence interval 17-70 months). Most relapses (68%) occurred in nodal regions. Relapses after pelvic nodal SBRT (n = 36) were located in the pelvis (n = 14), retroperitoneum (n = 1), pelvis and retroperitoneum (n = 8) or in non-nodal regions (n = 13). Relapses after SBRT for extrapelvic nodes (n = 5) were located in the pelvis (n = 1) or the pelvis and retroperitoneum (n = 4). Late grade 1 and 2 toxicity was observed in 17% (n = 12) and 4% of patients (n = 3). CONCLUSION: SBRT for oligometastatic PCa nodal recurrences is safe. Most subsequent relapses are again nodal and oligometastatic.

Significance of 18F-fluorocholine PET/CT positive pulmonary lesions in prostate cancer patients.

AIM: To assess the frequency and the significance of incidental pulmonary lesions with 18F-fluorocholine (18F-FCH) PET/CT in prostate cancer (PCa) patients. PATIENTS, METHODS: 225 consecutive PCa patients referred for 18F-FCH PET/CT (median age 68 years) were retrospectively evaluated for the presence of lesions in the lungs: 173 referred for restaging and 52 for initial staging regarding their high risk of extra prostatic extension. The final diagnosis was based on histopathological or on clinical and radiological follow-up. RESULTS: 13 patients had 18F-FCH positive pulmonary and 8 patients malignant lesions: 5 patients (38%) had a primary lung cancer (2 squamous cell carcinomas, 1 papillary adenocarcinoma, 1 typical pulmonary carcinoid, 1 bronchioloalveolar carcinoma) and 3 patients (23%) PCa metastases. Benign lesions were found in 5 subjects (38%). SUVmax and maximum diameter were neither significantly different in primary and metastatic tumors nor between malignant and benign lesions. CONCLUSIONS: Although our results suggest that incidental uptake in the lungs in PCa patients are nonspecific, their detection may have a significant impact on patient management knowing that more than 60% represent malignant disease.

A category-specific deficit of spatial representation: the case of autotopagnosia.

Following a vascular lesion in the parietal cortex of the language dominant hemisphere (right in one case), two patients showed a striking dissociation between spared naming, recognition and use of their body parts and an inability in localising on verbal command the same body parts on themselves and on a mannequin (Autotopagnosia, AT). The patients were submitted to a modified version of Reed and Farah Test (1995), a test that taps the ability to encode changes of body position as opposed to changes of position of objects. Their performance differed from normal controls, showing a specific deficit in encoding body position. It is suggested that AT could be the consequence of a lesion in a specific neural circuit, located in the language dominant hemisphere, whose function is to encode the body position for both oneself and others.

[Prostate-rectum spacers: optimization of prostate cancer irradiation]. / Spacers entre prostate et rectum : optimisation des techniques d'irradiation du cancer de la prostate.

In the curative radiotherapy of localized prostate cancer, improvements in biochemical control observed with dose escalation have been counterbalanced by an increase in radiation-induced toxicity. The injection of biodegradable spacers between prostate and rectum represents a new frontier in the optimization of radiotherapy treatments for patients with localized disease. Transperineal injection of different types of spacers under transrectal ultrasound guidance allows creating a 7-to-20 mm additional space between the prostate and the anterior rectal wall lasting 3 to 12 months. Dosimetrically, a relative reduction in the rectal volume receiving at least 70 Gy (V70) in the order of 43% to 84% is observed with all types of spacers, regardless of the radiotherapy technique used. Preliminary clinical results show for all spacers a good tolerance and a possible reduction in the acute side effects rate. The aim of the present systematic review of the literature is to report on indications as well as dosimetric and clinical advantages of the different types of prostate-rectum spacers commercially available (hydrogel, hyaluronic acid, collagen, biodegradable balloon).

Hypofractionated external beam radiotherapy to boost the prostate with ≥85 Gy/equivalent dose for patients with localised disease at high risk of lymph node involvement: feasibility, tolerance and outcome.

AIMS: To evaluate the tolerance and preliminary outcome of prostate cancer patients at high risk of lymph node involvement treated with normofractionated whole pelvic radiotherapy (WPRT) followed by a hypofractionated boost to the prostate with an intensity-modulated radiotherapy (IMRT) technique. MATERIALS AND METHODS: Between 2004 and 2011, 78 T1-4N0M0 prostate cancer patients at high risk of lymph node involvement (70 patients with a Roach index ≥ 15%; 57 with T-stage ≥ 3a; 40 with Gleason score ≥ 8) underwent WPRT to a median normofractionated dose of 50.4 Gy (range 48.0-50.4 Gy) with conformal three-dimensional techniques for most patients. A 24 Gy boost (4 Gy/six fractions, twice weekly) was delivered to the prostate with IMRT. The total median delivered dose was 74.4 Gy, equivalent to 85.2 Gy in 2 Gy/fractions (α/ß = 1.5 Gy). All patients underwent androgen deprivation for a total median time of 10.8 months. The maximum gastrointestinal and genitourinary acute and late toxicity scores were recorded according to the Radiation Therapy Oncology Group scoring system. RESULTS: All patients completed treatment as planned. Only 1% of patients presented with grade 3 genitourinary or gastrointestinal acute toxicity and none scored ≥ grade 4. With a median follow-up of 57 months, the 5 year probability of late grade ≥2 genitourinary and gastrointestinal toxicity-free survival was 79.1 ± 4.8% and 84.1 ± 4.5%, respectively. The 5 year biochemical disease-free survival, local relapse-free survival and distant metastasis-free survival were 84.5 ± 4.5%, 96.0 ± 2.8% and 86.4 ± 4.4%, respectively. A pre-radiotherapy prostate-specific antigen ≤0.3 ng/ml was associated with a better 5 year biochemical disease-free survival (P = 0.036) and distant metastasis-free survival (P = 0.049). CONCLUSIONS: The use of a hypofractionated IMRT boost after WPRT may allow a minimally invasive dose escalation to successfully treat patients with non-metastatic prostate cancer at high risk of lymph node involvement. Higher prostate-specific antigen values before radiotherapy may require alternative adjuvant treatments to further optimise the outcome of this high-risk group of patients.

[Total body irradiation: present and future]. / Irradiation corporelle totale : présent et avenir.

Total body irradiation (TBI) has an established role as preparative regimen for bone-marrow transplantation in the treatment of hematological malignancies. Many randomized trials demonstrated that the clinical outcomes obtained from the association of TBI and cyclophosphamide are equivalent, or, sometimes, better than those based on chemotherapeutic agents. Despite the therapeutic progress of the last years, and the consequent improvement in the overall survival, this preparative regimen remains always associated with a relatively high rate of acute and late toxicity. In this article, we review the actual indications of TBI in clinical practice, and analyze the technological progress in this domain. We focus on the hypothesis that a selective irradiation of the hematopoietic or lymphoid organs is actually possible with intensity-modulated radiotherapy. Technical limits and preliminary results in terms of acute and late toxicities of intensity-modulated TBI are analyzed. With these new technologies, treatment-related toxicity is not anymore a major limiting factor in the preparative regimens for bone-marrow transplantation, allowing for a larger spectrum of TBI indications, a possible extension to patients older than 50 years, or a dose escalation. Preliminary results warrant, however, further evaluation in clinical trials to better assess the impact of this new approach on disease control and the long-term toxicity.

Syntactic accuracy in sentence production: the case of gender disagreement in Italian language-impaired and unimpaired speakers.

We report three experiments with language-impaired and unimpaired speakers of Italian, assessing: (1) whether nonsyntactic (both conceptual and morphophonological) information is used in encoding the syntactic structure of a sentence; and (2) whether the integration of syntactic and non-syntactic information can be differentially impaired in Broca's aphasics. In all the experiments, gender agreement errors between a noun, subject of the sentence, and a predicative adjective were induced by presenting participants with sentence fragments to complete. The first experiment assessed the role of conceptual information. The second experiment investigated whether agreement is disrupted by the presence of another noun with different gender in the subject noun phrase. In the last experiment, we assessed whether morphophonological cues are used. We found that both populations used nonsyntactic information (both conceptual and morphophonological). However, patients were disrupted to a greater extent than normals by the presence of a gender mismatching noun in the subject noun phrase. The results are discussed in terms of how information integration during production is achieved and how it can be disrupted in aphasia.