Systemic Induction Chemotherapy Research Articles

Benefit of Neoadjuvant Laparoscopic Hyperthermic Intraperitoneal Chemotherapy and Bidirectional Chemotherapy for Patients with Gastric Cancer with Peritoneal Carcinomatosis Considering Cytoreductive Surgery

Comprehensive treatment comprising neoadjuvant laparoscopic HIPEC (L-HIPEC) and bidirectional intraperitoneal and systemic induction chemotherapy (BISIC) followed by cytoreductive surgery (CRS) for gastric cancer with peritoneal carcinomatosis (PC) has been developed. However, its benefits and patient selection criteria have not been thoroughly investigated. We retrospectively reviewed 113 patients, with 25 having received comprehensive treatment (L-HIPEC, BISIC, and then CRS-HIPEC; the BISIC group) and 88 having received direct CRS-HIPEC (the CRS group). The BISIC group showed greater tumor clearance in terms of post-CRS peritoneal cancer index ((PCI) 6 vs. 14, p = 0.002) compared to CRS group. The median survival was 20.0 months in the BISIC group and 8.6 months in the CRS group (p = 0.031). Multivariable analysis revealed that the factors associated with increased survival were the BISIC protocol, age, and post-CRS tumor clearance. BISIC significantly improved survival in cases of moderate severity (PCI 11–20) and severe cases (PCI 21–39) without increasing the morbidity rate. We recommend the use of this neoadjuvant strategy for patients with gastric cancer-associated PC and an initial PCI of >10 to provide superior survival outcomes.

A Patient With Stage III Locally Advanced Pancreatic Adenocarcinoma Treated With Intra-Arterial Infusion FOLFIRINOX: Impressive Tumoral Response and Death due to Legionella pneumophila Infection: A Unique Case Report.

Patients affected by pancreatic ductal adenocarcinoma (PDAC) have very poor prognosis, whereby at a follow-up of 5 years, the mortality rate is very similar to the incidence rate. Globally, around 10% of patients are amenable to radical surgery at the time of diagnosis, which represents the only chance of cure or long-term survival for these patients. Almost 40% of patients with PDAC show locally advanced pancreatic cancer (LAPC). LAPC is not a metastatic disease, although it is not amenable to radical surgery. For these patients, systemic induction chemotherapy with intravenous FOLFIRINOX (5-fluorouracil, folic acid, irinotecan, oxaliplatin) regimen is administered, with the aim of conversion to surgery, although the conversion rate remains low, at approximately 10% to 15%. Pancreatic arterial chemotherapy has been explored to overcome the intrinsic tumor pancreatic resistance to systemic chemotherapy, where an intra-arterial port-a-cath is placed by means of interventional oncology techniques under angiographic guidance in the operating theater. Here, we treated a patient with an intra-arterially modified FOLFIRINOX regimen. Three courses were administered, and the patient experienced no adverse events. At the end of the third course, the patient rapidly developed lung failure due to nosocomial Legionella pneumophila infection, despite the impressive pathological tumor response shown in the autopsy report. This is a first and unique report that demonstrates that pancreatic intra-arterial FOLFIRINOX can be safe and efficacious. We believe that this preliminary result will be confirmed in the next patients to be enrolled and that it provides a glimmer of hope for patients with this lethal disease.

Treatment intensification with hepatic arterial infusion chemotherapy in patients with liver-only colorectal metastases still unresectable after systemic induction chemotherapy \u2013 a randomized phase II study -- SULTAN UCGI 30/PRODIGE 53 (NCT03164655)- study protocol

BackgroundApproximately 40% of colorectal cancer patients will develop colorectal liver metastases (CRLM). The most effective approach to increase long-term survival is CRLM complete resection. Unfortunately, only 10–15% of CRLM are initially considered resectable. The objective response rates (ORR) after current first-line systemic chemotherapy (sys-CT) regimens range from 40 to 80% and complete resection rates (CRR) range from 25 to 50% in patients with initially unresectable CRLM. When CRLM patients are not amenable to complete resection after induction of sys-CT, ORRs obtained with second-line sys-CT are much lower (between 10 and 30%) and consequently CRRs are also low (< 10%). Hepatic arterial infusion (HAI) oxaliplatin may represent a salvage therapy in patients with CRLM unresectable after one or more sys-CT regimens with ORRs and CRRs up to 60 and 30%, respectively. This study is designed to evaluate the efficacy of an intensification strategy based on HAI oxaliplatin combined with sys-CT as a salvage treatment in patients with CRLM unresectable after at least 2 months of first-line induction sys-CT.Objectives and endpoints of the phase II studyOur main objective is to investigate the efficacy, in term of CRR (R0-R1), of treatment intensification in patients with liver-only CRLM not amenable to curative-intent resection (and/or ablation) after at least 2 months of induction sys-CT. Patients will receive either HAI oxaliplatin plus systemic FOLFIRI plus targeted therapy (i.e. anti-EGFR antibody or bevacizumab) or conventional sys-CT plus targeted therapy (i.e. anti-EGFR or antiangiogenic antibody). Secondary objectives are to compare: progression-free survival, overall survival, objective response rate, depth of response, feasibility of delivering HAI oxaliplatin including HAI catheter-related complications, and toxicity (NCI-CTCAE v4.0).MethodsThis study is a multicenter, randomized, comparative phase II trial (power, 80%; two-sided alpha-risk, 5%). Patients will be randomly assigned in a 1:1 ratio to receive HAI oxaliplatin combined with systemic FOLFIRI plus targeted therapy (experimental arm) or the best sys-CT plus targeted therapy on the basis of their first-line prior sys-CT history and current guidelines (control arm). One hundred forty patients are required to account for non-evaluable patients.Trial registrationClinicalTrials.gov, (NCT03164655). Trial registration date: 11th May 2017.

Impact of Upfront Chemotherapy on Overall Survival in Isolated Myeloid Sarcoma

Introduction Myeloid sarcoma (MS) is a tumor composed of myeloid blasts occurring at a site other than the bone marrow. MS may precede or coincide with acute myeloid leukemia (AML) or may also be an initial manifestation of relapse. Although the majority of isolated MS progress to AML, not all of them do. Due to its rarity and lack of prospective studies, there is no consensus for MS treatment; patients receive local treatment with radiotherapy, surgery, or both. In addition, due to progression to AML in the majority of patients treated with local therapies, systemic induction chemotherapy has also been used upfront in patients newly diagnosed with MS. However, it is unclear if chemotherapy can be avoided until patients develop AML, sparing some patients from intensive chemotherapy. In the current study, we utilize a large national database to compare the overall survival of MS patients treated with local therapies (radiation and/or surgery) versus patients treated with upfront chemotherapy combined with local therapies. Methods The National Cancer Database (NCDB) was used to extract cases of MS from 2004 to 2016 using the ICD-O-3 code 9930 (myeloid sarcoma). This multi-institutional database covers about 70% of the US population and has many important covariates like income level and comorbidities. It includes information on which treatment modalities were used and when they were performed. However, it does not include details on the exact chemotherapeutic agents and the number of cycles that patients received. Cases with unknown survival, development of MS after a previous malignancy, without histologic confirmation of the disease, bone marrow as primary site, and age less than 1 year old or more than 75 years old were excluded. In order to account for immortal-time bias due to variability in time from diagnosis to receipt of upfront treatment, we performed time-to-event landmark analysis. Since leukemic evolution usually starts occurring 3-6 months from diagnosis, we chose a landmark time of 60 days a priori. We excluded patients that survived less than 60 days and defined upfront treatment as any treatment that was received within 60 days after diagnosis. To exclude cases with disease not amenable to localized therapies, we excluded patients that did not receive surgery or radiation by the 60-day mark. To account for confounding, propensity scores for upfront chemotherapy administration were calculated using logistic regression. Inverse probability treatment weighting (IPTW) was used to calculate stabilized weights. Standardized bias (SB) was calculated among covariates before and after weighting. When the SBs were smaller than 0.10, groups were considered to be well-balanced. In the weighted cohort, overall survival was compared between the two groups using the inverse probability of treatment-weighted log-rank test and weighted survival functions were plotted. The hazard ratio was calculated with propensity-score weighted Cox proportional-hazard model and robust variance estimations was used to account for the sample weights. Statistical analysis was performed using STATA 15.1. Results A total of 1258 cases were retrieved from the NCDB. Of those, 151 cases met the criteria for the study (Figure 1). As only four cases were missing data, we performed a complete case analysis. As a result, 147 cases were included in the study and the prediction of the propensity score. After IPTW, the covariates were well-balanced between the two cohorts as shown in Table 1. In survival analysis, 82 events occurred during follow-up. The IPTW Kaplan-Meier analysis demonstrated no significant difference in the overall survival among isolated MS patients with localized treatments plus upfront chemotherapy versus localized treatment alone (log-rank P= 0.722, Figure 2). Conclusion We found no significant difference in overall survival among isolated MS patients who received localized treatment plus upfront chemotherapy versus localized treatment alone. This data suggests that MS patients can avoid upfront induction chemotherapy and its related complications. With this approach, some patients that will never develop AML may be spared from induction chemotherapy altogether. However, patients that are not treated with upfront chemotherapy should have close follow-up with bone marrow biopsies utilizing flow cytometry or molecular approaches to detect submicroscopic disease before they develop fulminant AML. Disclosures No relevant conflicts of interest to declare.

Induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CCRT) in nasopharyngeal carcinoma(NPC) patients treated between 2004 and 2016: Patient and treatment characteristics and long term outcome.

e17507 Background: Standard treatment of locoregionally advanced nasopharyngeal carcinoma (LRA-NPC) is CCRT with or without adjuvant chemotherapy (CT). The value of adding IC to CCRT in LRA-NPC is unclear. We aimed to retrospectively evaluate LRA-NPC patients treated with IC followed by CCRT and analyse patient, tumor, treatment characteristics and outcome. Methods: Between 2004 and 2016, 202 patients with nonmetastatic LRA-NPC (stage 3-4), 144 males and 58 females ranging from 17 to 75 (median 49) years old were treated with IC followed by CCRT. Eleven (%5.4) patients had keratinised (WHO I), and 191 (%94.6) had nonkeratinised or undiffrentiated (WHO II-III) carcinoma. Cumulative radiation dose to primary tumor ranged from 60 to 74 (median 70) Gy. Ninety-one (%45) of the patients received 2-dimensional and 111 (%55) received intensity modulated radiotherapy (IMRT). IC consisted of taxane (T)(75 mg/ m2) and platinum (P)(75 mg/m2) combination (199 patients) or P and fluoruracil or epirubicine (3 patients) combination and 188 of the patients received 3 cycles of IC. Concomittant P was used either weekly (40 mg/m2, 25 patients) or every 3-weekly (100 mg/m2, 177 patients) application. Follow-up ranged from 5 to 167 months (median, 72.5 months). Results: Treatment failure was observed in 52 (%25.7) of the patients (21 local, 13 regional and 27 distant failures). Distant failure rate of all the patients exceeds 13%. Five and 10 years disease free survival (DFS) rates are 75.2% and 70.4% and overall survival (OS) rates are 78.9% and 64% respectively. In univariate analysis patient age favoring those below 49 and stage of disease favoring WHO II-III were all significant predictors of DFS and OS. In addition pathology was a significant predictor of DFS. Conclusions: LRA-NPC patients treated with IC followed by CCRT have a high locoregional control rate. Despite the use of systemic (induction) chemotherapy distant control remains insufficient and continues to be a challenge in NPC treatment. Besides improving locoregional control more effective systemic therapy is needed. [Table: see text]

PRODIGE 53-UCGI 30 (SULTAN): A randomized phase II study comparing treatment intensification with hepatic arterial infusion chemotherapy plus systemic chemotherapy to systemic chemotherapy alone in patients with liver-only colorectal metastases considered still non resectable after at least two months of systemic induction chemotherapy.

TPS3619 Background: In the first-line setting, current combination chemotherapy (CT) achieve high objective response rates (ORR) ranging from 40% to 80% and leads to complete resection rate (CRR) of colorectal cancer liver metastasis (CRCLM) in 25% to 50% of patients with initially non-resectable CRLM. However, when patients with CRLM are still not amenable to resection after induction CT, ORRs (~5-30%) and CRRs ( &lt; 10%) obtained with second-line systemic CT are much lower. Combining hepatic arterial infusion (HAI) and systemic (SYS) CT for unresectable CRLM lead to high ORR and the potential of cure in the second-line and further setting. Methods: This multicenter randomized phase II trial conducted in 20 centers in France plans to include 140 patients with CRLM still not amenable to a curative intent-treatment after at least two months of first-line induction SYS CT whatever the tumor response. Patients are randomized (1:1) between intensified biweekly regimen combining HAI oxaliplatin (100 mg/m²) and SYS FOLFIRI (leucovorin 400 mg/m², irinotecan 180 mg/m², and 5-FU 2.4 g/m²over 48 h) plus cetuximab 500 mg/m² or bevacizumab 5 mg/kg (according to RAS status and prior response/tolerance to SYS induction CT) or SYS CT alone according to current guidelines. The primary endpoint is to evaluate and compare the curative-intent (R0-R1) resection (and/or ablation) rate (CRR) of CRLM in both arms. A gain of 20% in CRR is expected (30% in the experimental arm vs. 10% in the control arm; α 5% [two-sided]; β 20%). Stratification factors at randomization are prior adjuvant or SYS induction oxaliplatin-based CT, tumor response to SYS induction CT, and center. Secondary endpoints include progression-free (overall, hepatic and extrahepatic) and overall survival, ORR, relative change in the sum of longest diameters of RECIST target lesions (DoR) and feasibility/tolerability. Since study start, 3 patients have been enrolled to date (planned accrual period: 3 years). Clinical trial information: NCT03164655.

A new bidirectional intraperitoneal and systemic induction chemotherapy (BISIC) for the peritoneal metastasis from gastric cancer in neoadjuvant setting

A phase II study to evaluate the efficacy and safety of a Bidirectional intraperitoneal and systemic induction chemotherapy (BISIC) were performed in patients with Peritoneal metastasis (PM) from gastric cancer in neoadjuvant setting. Sixty-one patients were treated with oral administration of S1 (60 mg/m 2 /day) for 14 consecutive days, followed by 7 days rest, plus intraperitoneal (i.p.) and intravascular (i.v.) administration of docetaxel and cisplatin (30 mg/m2 each) on day 1 and on day 8. The treatment course was repeated every 3 weeks for 3 times. Positive cytological results in 38 patients before BISIC became negative in 27 (71.1%) patients after BISIC. After BISIC, 44 patients received laparotomy and CRS, and complete cytoreduction was achieved in 28 of 44 patients (64%). During BISIC, side effects of grade 3 and 4 were found in 6 (9.9%) patients. After CRS, 7 (15.8%) and 3 (6.8%) patients developed Grade 3 and 4 complications. The overall operative mortality rate was 4.5% (2/44). Histologic effects on primary tumors were found in 87.9% (29/33 tumors). Complete histologic disappearance of PM was observed in 10 (22.7%) of 44 patients. Median survival time (MST) was 15.1 months, with a one and two-year survival of 62.4%, and 44.0%. BISIC therapy is safe and effective in gastric cancer patients with PM.

Outcome Data of Patients with Peritoneal Carcinomatosis from Gastric Origin Treated by a Strategy of Bidirectional Chemotherapy Prior to Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy in a Single Specialized Center in Japan

Management of peritoneal disseminated gastric cancer (GC) remains a challenging problem. The purpose of our study was to evaluate the outcome of bidirectional induction chemotherapy [bidirectional intraperitoneal and systemic induction chemotherapy (BIPSC)] in patients with peritoneal carcinomatosis (PC) arising from GC who underwent cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Overall, 194 patients with PC arising from GC were treated with BIPSC comprising intraperitoneal docetaxel at a dose of 20 mg/m(2) and cisplatin at a dose of 30 mg/m(2) followed by four cycles of oral S-1 at a dose of 60 mg/m(2). CRS and HIPEC were performed in responders to BIPSC. Of these 194 patients, 152 (78.3 %) underwent CRS and HIPEC between January 2005 and December 2012. Treatment-related mortality was 3.9 %, and major complications occurred in 23.6 % of patients. The median survival rate was 15.8 months, with 1-, 2-, and 5-year survival rates of 66, 32 and 10.7 %, respectively, in the patients treated with combined treatment. Multivariate analysis identified pathologic response to BIPSC (p = 0.001), low tumor burden [peritoneal cancer index (PCI) ≤ 6] (p = 0.001), and completeness of CRS (CC-0, CC-1) (p = 0.001) as independent predictors for a better prognosis. As a viable option, BIPSC with CRS and HIPEC for patients with PC arising from GC may be performed safely, with acceptable morbidity and mortality, in a specialized unit. Response to BIPSC, optimal CRS and limited peritoneal dissemination seem to be essential to achieve the best outcomes in these patients.

Treatment of early childhood medulloblastoma by postoperative chemotherapy and deferred radiotherapy

To investigate the utility of postoperative chemotherapy in delaying radiotherapy and to identify prognostic factors in early childhood medulloblastoma, we studied children younger than 3 years of age registered to the HIT-SKK'87 (Therapieprotokoll für Säuglinge und Kleinkinder mit Hirntumoren [Brain Tumor Radiotherapy for Infants and Toddlers with Medulloblastoma] 1987) trial who received systemic interval chemotherapy until craniospinal radiotherapy was applied at 3 years of age or at relapse, from 1987 to 1993. Children with postoperative residual tumor or metastatic disease received systemic induction chemotherapy prior to interval chemotherapy. Twenty-nine children were eligible for analyses (median age, 1.7 years; median follow-up, 12.6 years). In children without macroscopic metastases, rates (+/-SEM) for 10-year progression-free survival (PFS) and overall survival (OS) were 52.9% +/- 12.1% and 58.8% +/- 11.9% (complete resection), and 55.6% +/- 16.6% and 66.7% +/- 15.7% (incomplete resection), compared with 0% and 0% in children with macroscopic metastases. Survival was superior in nine children with desmoplastic or extensive nodular histology compared with 20 children with classic medulloblastoma (10-year PFS, 88.9% +/- 10.5% and 30.0% +/- 10.3%, p = 0.003; OS, 88.9% +/- 10.5% and 40.0% +/- 11.0%, p = 0.006). Eleven of 12 children with tumor progression during chemotherapy had classic medulloblastoma. After treatment, IQ scores were inferior compared with nonirradiated children from the subsequent study, HIT-SKK'92. Classic histology, metastatic disease, and male gender were independent adverse risk factors for PFS and OS in 72 children from HIT-SKK'87 and HIT-SKK'92 combined. In terms of survival, craniospinal radiotherapy was successfully delayed especially in young children with medulloblastoma of desmoplastic/extensive nodular histology, which was a strong independent favorable prognostic factor. Because of the neurocognitive deficits of survivors, the emerging concepts to avoid craniospinal radiotherapy should rely on the histological medulloblastoma subtype.

Concomitant Administration of Weekly Oxaliplatin, Fluorouracil Continuous Infusion, and Radiotherapy After 2 Months of Gemcitabine and Oxaliplatin Induction in Patients With Locally Advanced Pancreatic Cancer: A Groupe Coordinateur Multidisciplinaire en Oncologie Phase II Study

According to previously reported Groupe Coordinateur Multidisciplinaire en Oncologie (GERCOR) studies in locally advanced pancreatic cancer (LAPC), concomitant chemoradiotherapy (CCRT) may be recommended for patients who do not experience disease progression after systemic induction chemotherapy (CT). To further improve patient outcome with classical fluorouracil (FU)-based CCRT, this study was designed to prospectively investigate a CCRT with FU infusion and weekly oxaliplatin after 2 months of gemcitabine and oxaliplatin (GEMOX) induction chemotherapy. Nonpretreated patients with LAPC having WHO performance status (PS) of 0 to 2 received four induction cycles of GEMOX (gemcitabine 1 g/m(2) on day 1 and oxaliplatin 100 mg/m(2) on day 2; day 1 of a 15-day cycle). One month after cycle 4, patients who did not experience disease progression with PS 0 to 2 received 45 Gy over 5 weeks + 10 Gy (as a concomitant boost during the last 2 weeks) of radiotherapy (RT), with daily 250 mg/m(2) FU as a continuous infusion and 60 mg/m(2)of oxaliplatin weekly. Of 59 patients, 50 patients (84.7%) received CCRT, whereas nine patients did not because of disease progression (seven patients), CT toxicity (one patient), or personal decision (one patient). Forty-four patients (74.5%) completed the fully planned CCRT. Median progression-free survival and overall survival durations were 7.6 and 12.2 months, respectively, for the whole population and 9.4 and 12.6 months, respectively, for patients who completed CCRT. CCRT grade 3 to 4 toxicities (National Cancer Institute Common Toxicity Criteria) were neutropenia (10.4%), thrombocytopenia (8.4%), nausea and vomiting (16.7%), and diarrhea (12.5%). Concomitant administration of weekly oxaliplatin, continuous-infusion FU, and RT in patients with LAPC is feasible, with an acceptable acute and late safety profile. The encouraging results observed despite a nonoptimal patient selection (owing to the short induction time) indicates that further randomized evaluation to better define the specific role of oxaliplatin in CCRT is deserved.

Response to intraarterial induction chemotherapy: A prognostic parameter in oral and oropharyngeal cancer

Patients with head and neck cancer and good pathologic response to neoadjuvant systemic induction chemotherapy have a better prognosis for survival than do those with stable or progressive disease. Thus, induction chemotherapy could theoretically help in stratifying further treatment, but toxicity is much too high. The prognostic implication of superselective intraarterial high-dose cisplatin administered by a femoral approach, which has much less toxicity, is not yet known. One hundred eighty-seven unselected consecutive patients with previously untreated oral and oropharyngeal squamous cell carcinoma received intraarterial high-dose cisplatin for induction and were assessed for response by visual examination and palpation. This treatment was followed by surgery and adjuvant radiation with concomitant systemic chemotherapy. Omission of a modality depended on individual contraindications and not on preselection. The consequence of omissions has been the constitution of several treatment arms. The overall and disease-free survival in relation to clinical local response after intraarterial induction chemotherapy was calculated using the Kaplan-Meier method. Additional analysis excluded bias caused by stages and treatment arms. Explorative statistics using the log-rank and chi-square tests demonstrated a strong prognostic relevance of response to intraarterial chemotherapy irrespective of stage and treatment. Our results are encouraging for prospective randomized studies and molecular genetic investigations with intraarterial chemotherapy.

Advanced carcinoma of the larynx: Results of surgery and radiotherapy without induction chemotherapy (1980–1985): A multivariate analysis

Purpose: Induction chemotherapy has been proposed in the case of advanced laryngeal cancer in order to preserve laryngeal function in those patietns who are complete responders. To clarify the treatment policies, a restrospective multicentric analysis of 116 patients with advanced carcinoma of the larynx treated by radical surgery and postoperative radiotherapy was carried out in order to evaluate prognostic factors for local control and survival.Methods and Materials: Between 1980 and 1985, 116 patients with Stage III squamous cell carcinoma of the larynx underwent radical surgery and postoperative radiotherapy with a curative intent. Treatments were very homogenous, and doses delivered were in the range of 50–65 Gy according to nodal involvement and surgical margins status.Results: The local recurrence rate and the local disease-free survival rate at 5 years were 22.5% and 76.3%, respectively. Actuarial survival at 5 years was 68.3% with 44 patients stil alive who no evidence of disease (NED) with more than 5 years follow-up. For both overall survival and relapse-free survival, cervical node involvement with capsular rupture was found to be the only significant adverse pronostic factor in univariate and multivariate analysis. No other parameter was predictive either for local recurrence or for survival.Conclusions: Local prognosis and survival depend largely on nodal involvement and capsular rupture while increasing doses of radiation strategy is likely to reduce the risk of local and nodal recurrence. Preservation of functional larynx is certainly an important goal to achieve when treating advanced carcinoma of the larynx, provided that local failure rate and survival be similar. In the unique randomized study previously published in the literature comparing radical surgery and postoperative radiotherapy to induction chemotherapy and radiotherapy, the local-regional failure rate was drastically increased in the chemotherapy arm. Other results from well-designed controlled studies are awaited before recommending systemic induction chemotherapy and larynx preservation in complete responders. On the other hand, testing synchronous or alternated chemotherapy vs. induction chemotherapy may address the pending questions about the optimal treatment of advanced laryngeal carcinoma.

Systemic induction chemotherapy for locally advanced breast cancer

Systemic induction chemotherapy for locally advanced breast cancer

PRETREATMENT TESTICULAR BIOPSY IN CHILDHOOD ACUTE LYMPHOCYTIC LEUKAEMIA

Between August, 1978, and March, 1981, 24 boys with acute lymphocytic leukaemia (ALL) (14 non-B-cell non-T-cell, 6 pre-B-cell, and 4 T-cell) underwent bilateral wedge testicular biopsy at initial diagnosis. All testes were of normal size. Histological analysis was performed independently by three pathologists, 4 (3 non-B non-T, and 1 pre-B) of 20 patients with non-T-cell ALL demonstrated testicular focal lymphoblastic involvement. Successful induction chemotherapy without concomitant testicular irradiation completely eradicated testicular infiltrates in all 4 patients. Only 1 of the 4 T-cell patients had pre-treatment testicular infiltrates. Unlike boys with non-B non-T leukaemia, attainment of bone-marrow remission in this patient was associated with persistent testicular disease. These preliminary data indicate that in patients with ALL of non-T-cell type, systemic induction chemotherapy eradicates the small testicular infiltrates of lymphoblasts. Prophylactic testicular irradiation in this group of patients does not seem to be warranted.

Chorea associated with a subdural hematoma in a child with leukemia

Patient M. H., a 12-year-old Caucasian boy, developed acute lymphocytic leukemia in February, 1968, and was given systemic induction and maintenance chemotherapy, without central nervous system prophylaxis. A lumbar puncture performed in May, 1968, because of recurrent headache, lethargy, and vomiting, revealed 30 lymphoblasts/mm ~ CSF. A single dose of intrathecal methotrexate resulted in clearing of spinal fluid and resolution of the symptoms. A lumbar puncture two months later was normal. The child remained free of central nervous system symptoms until 1974. Bone marrow relapses in January and August, 1969, and February, 1970, were effectively treated. In December, 1974, massive weight gain, headache, nausea, and vomiting led to a diagnosis of meningeal leukemia with hypothalamic syndrome. The CSF contained 490 lymphoblasts/ mm -~, Results of a brain scan and EEG were normal. I ntrathecally administered cytosine arabinoside and methotrexate resulted in clearing of the spinal fluid and regression of symptoms. Only mild headache and nausea persisted. Intrathecal methotrexate was given weekly until February, 1975, and then administered monthly. In March, 24 hours after receiving intrathecal methotrexate, he developed a severe headache, nausea, and vomiting. In the following two weeks the parents noted increasing nervousness, incoordination, and unusual movements involving the patient's face, trunk, and extremities. His speech was difficult to understand. In retrospect, the parents felt that the abnormal movements may have preceded the lumbar puncture. No seizure activity was observed, but he periodically appeared to be dazed.