Site Of Relapse In Patients Research Articles

Abstract PD3-12: Central nervous system as first site of relapse in patients with HER2 positive early breast cancer treated in the BCIRG-006 trial

Abstract Introduction: Central Nervous System (CNS) metastases as first site of relapse is seen in 2-3% of patients with HER2+ early breast cancer (EBC) during or after treatment with adjuvant trastuzumab. Data about long-term follow-up outcomes in this population is scarce. Methodology: BCIRG-006 was designed to assess the efficacy and safety of two trastuzumab-based regimens compared to a standard (non-trastuzumab) regimen in the adjuvant treatment of HER2+ EBC. 3,222 patients were randomized to standard AC-T or two trastuzumab-based regimens (AC-TH or TCH). Ten year follow-up outcomes were previously presented; we have used this data to assess the frequency and course of CNS relapses as first site of distant recurrence. DFS and OS in these patients were estimated and compared using the Kaplan-Meier method and Log-Rank test respectively. Univariate and multivariate analyses for DFS were conducted considering patient's age, nodal status, tumor size and estrogen receptor (ER) status in the primary tumor. Results: Of the 3,222 patients randomized, 575 (17.8%) experienced a distant relapse and in 17.5% of these (n=101) CNS was the first site of recurrence. With a median follow-up of 10.3 years, the frequency of CNS relapses did not differ when comparing the trastuzumab containing arms with the control arm (OR 0.86, 95% CI: 0.56-1.33; p= 0.519). No difference was observed either between AC-TH and TCH (OR 1.14, 95% CI: 0.67-1.94; p= 0.704). There were no differences in DFS (HR 1.21, 95% CI: 0.74-1.99; p= 0.621) nor in OS (HR 0.74, 95% CI: 0.43-1.27; p= 0.377) between AC-T, AC-TH and TCH arms. Positive axillary nodes (≥4 nodes) and ER negative status at baseline remained independent risk factors for CNS relapse after univariate and multivariate analysis (HR 0.60, 95% CI: 0.8-0.95; p= 0.007 for nodal status and HR 0.56, 95% CI: 0.37-0.85; p= 0.029 for ER status). Conclusion: Among the pivotal adjuvant trastuzumab trials, BCIRG-006 is the one with the longest median FUP in which data about CNS relapses has been presented. CNS relapse in patients in this trial was an infrequent event. Its frequency and outcomes were similar across the three treatment arms. Patients with ER negative and/or ≥ 4 positive nodes are at higher risk of CNS relapse irrespective of trastuzumab therapy and may be the patient population where research efforts should be focused. BC outcomes in patients with CNS metastases per treatment arm in the BCIRG-006 trial AC-T N=1073 n(%)AC-TH N=1074 n(%)TCH N=1075 n(%)p valueFrequency of CNS relapse37 (3.44%)30 (2.79%)34 (3.16%)0.519 ^Median DFS (months; 95% CI)23.8 (13.3-30.4)19.9 (16.6-25.1)19.9 (15.0-27.2)0.621 ⫲Median OS (months; 95% CI)42.5 (28.3-62.7)53.2 (31.2-103.6)30.3 (23.4-39.0)0.377 ⫲ ^ comparing control vs. trastuzumab-containing arm using Fisher's Exact test. ⫲ comparing control vs. trastuzumab-containing arms using Log Rank test. Citation Format: Chan A, Spera G, Machado A, Fung H, Bee V, Fresco R, Slamon DJ. Central nervous system as first site of relapse in patients with HER2 positive early breast cancer treated in the BCIRG-006 trial [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr PD3-12.

Assessment of HER2 status in adenocarcinomas of the stomach or gastroesophageal junction in a Western population.

e15548 Background: HER2 status is a predictive biomarker to response to trastuzumab in metastatic adenocarcinomas of the stomach our gastroesophageal junction. However, relatively little is known about the role of HER2 in the non-metastatic disease in western population. Methods: This study included 106 patients with gastric cancer who underwent surgery between January 2007 and June 2014 at Universitary Hospital of Santiago de Compostela. Immunohistochemical expression of HER2 was analyzed using the DAKO-HercepTest™ and gene amplification using DAKO-DuoCISH kit; both was scored according to published reports. Correlations between HER2 status, clinicopathological characteristics, survival and relapse sites were retrospective analyzed. Results: HER2 expression rate by IHC was: 76 patients (71.7%) classificated as negative, 7 patients (6.6%) as positive and 23 patients (21.7%) as equivocal. HER2 gene amplification by DuoCISH was positive in 14 patients (13.2%). HER2 status was associated with intestinal subtype (p = 0.010), tumor grade (well-moderately differentiated, p = 0.008), lower tumor invasion (p 0.018) and distant relapse (p = 0.048). There was a significant interaction between HER2 status and significantly worse disease-free survival (DFS) (P = 0.039) and overall survival (OS) (P = 0.028), respectively. Conclusions: In our population, HER2 status appears to be associated with differentiated clinicopathological characteristic, worse OS and DFS and distant site of relapse in patients with resected gastric cancer.

Features, risk factors and clinical outcome of "very late" recurrences after surgery for localized renal carcinoma: A retrospective evaluation of a cohort with a minimum of 10 years of follow up.

To evaluate the features and the predictors of "very late" recurrences after surgery for localized renal cell carcinoma. Since 1983, an institutional database with data of more than 2300 consecutive patients treated for renal cancer has been prospectively maintained. Patients N0 /Nx M0 followed for a minimum of 10 years without recurrences were retrieved. The site, time and treatment of recurrences observed afterwards were recorded, and the predictors were investigated by Cox regression analysis. A total of 554 patients (231 women, 323 men; age 59.3 ± 11.6 years) followed for a mean/median time of 15.1/13.6 years (range 10.0-34.1 years) were analyzed. A recurrence was observed in 26 patients (4.6%) after a mean/median interval of 13.3/12.3 years (range 10.5-30.2 years). The pathological stage 2/3 was the only independent predictor of recurrence (P = 0.003), and it was related also to the latency of recurrence (mean/median latency 15.4/14.0, 11.4/10.8 and 12.5/12.0 years, respectively, for stage 1, 2 and 3; P < 0.005 for stage 1 vs stage 2 or 3). The contralateral kidney was the most frequent site of relapse in patients with stage pT1, whereas multiple sites were more frequent for stage pT2 and pT3. The risk of a "very late" recurrence of renal cancer is approximately 5%, and it depends on the pathological stage. For stage pT1, the kidney/s should be surveilled for indefinite time, preferably by ultrasound to reduce the X-ray exposition; for stage pT2 and pT3, the abdomen and the lungs should be monitored, by computed tomography scan during the first years, and then by abdominal ultrasound and chest X-ray.

Evaluation of the Lactate-to-N-Acetyl-aspartate Ratio Defined With Magnetic Resonance Spectroscopic Imaging Before Radiation Therapy as a New Predictive Marker of the Site of Relapse in Patients With Glioblastoma Multiforme

Because lactate accumulation is considered a surrogate for hypoxia and tumor radiation resistance, we studied the spatial distribution of the lactate-to-N-acetyl-aspartate ratio (LNR) before radiation therapy (RT) with 3D proton magnetic resonance spectroscopic imaging (3D-(1)H-MRSI) and assessed its impact on local tumor control in glioblastoma (GBM). Fourteen patients with newly diagnosed GBM included in a phase 2 chemoradiation therapy trial constituted our database. Magnetic resonance imaging (MRI) and MRSI data before RT were evaluated and correlated to MRI data at relapse. The optimal threshold for tumor-associated LNR was determined with receiver-operating-characteristic (ROC) curve analysis of the pre-RT LNR values and MRI characteristics of the tumor. This threshold was used to segment pre-RT normalized LNR maps. Two spatial analyses were performed: (1) a pre-RT volumetric comparison of abnormal LNR areas with regions of MRI-defined lesions and a choline (Cho)-to- N-acetyl-aspartate (NAA) ratio ≥ 2 (CNR2); and (2) a voxel-by-voxel spatial analysis of 4,186,185 voxels with the intention of evaluating whether pre-RT abnormal LNR areas were predictive of the site of local recurrence. A LNR of ≥ 0.4 (LNR-0.4) discriminated between tumor-associated and normal LNR values with 88.8% sensitivity and 97.6% specificity. LNR-0.4 voxels were spatially different from those of MRI-defined lesions, representing 44% of contrast enhancement, 64% of central necrosis, and 26% of fluid-attenuated inversion recovery (FLAIR) abnormality volumes before RT. They extended beyond the overlap with CNR2 for most patients (median: 20 cm(3); range: 6-49 cm(3)). LNR-0.4 voxels were significantly predictive of local recurrence, regarded as contrast enhancement at relapse: 71% of voxels with a LNR-0.4 before RT were contrast enhanced at relapse versus 10% of voxels with a normal LNR (P<.01). Pre-RT LNR-0.4 in GBM indicates tumor areas that are likely to relapse. Further investigations are needed to confirm lactate imaging as a tool to define additional biological target volumes for dose painting.

Post-progression survival after treatment with epidermal growth factor receptor-tyrosine kinase inhibitor for advanced non-small cell lung cancer patients harboring epidermal growth factor receptor mutations.

e19005 Background: Non-small cell lung cancer (NSCLC) patients harboring the epidermal growth factor receptor (EGFR) mutation show a survival benefit on treatment with EGFR-tyrosine kinase inhibitor (EGFR-TKI); however, few studies report on post-progression tumor behavior after treatment with EGFR-TKI. Methods: We retrospectively reviewed clinical data of stage IV or recurrent NSCLC patients harboring the EGFR mutation, who received EGFR-TKI as first-line treatment in our institute from 2009 to 2011. Results: Thirty-six patients received EGFR-TKI as first-line therapy. Thirty of these patients with recurrent NSCLC were enrolled in this study. The median age of the patients was76 years (range, 38–97), and the male/female ratio was 4/26. The median progression-free survival (PFS) after EGFR-TKI treatment was 8.2 months. Sites of relapse in patients with progressive disease (PD) were the brain, pleural effusion, bone, and lung (n=5, 13, 6, and 8, respectively). Twenty-one patients received sequential therapy: 11 patients received continued EGFR-TKI treatment beyond PD and 10 patients received second-line therapy. Second-line therapies were platinum-based doublet therapy, monotherapy, and another cycle of EGFR-TKI (n = 6, 2, and 2 patients, respectively). Post-progression survival (PPS) of all the patients after treatment with EGFR-TKI was 9.2 months, whereas that of patients who received EGFR-TKI as second-line chemotherapy was 14 months. Subgroup analysis according to the site of relapse showed that after first-line EGFR-TKI treatment, PFS tended to be higher for patients with a relapse in the brain (11.6 months) than for patients with sites of relapse other than the brain (8.2 months). Conclusions: PPS after EGFR-TKI therapy in patients treated with second-line chemotherapy was similar to the OS of NSCLC patients without an EGFR mutation. Subgroup analysis showed that patients with a relapse in the brain might survive longer.

Tumor angiogenesis as predictive factor for site of relapse in patients with gastric cancer: Biological and clinical implications.

e21119 Background: Tumor integrins are relevant for gastric cancer diffusion. Preclinical studies suggested that angiogenesis is also crucial for metastatic spread. We investigated the role of VEGF and VEGF-R genotyping and integrin polymorphisms in determining either peritoneal or hematogenous metastases in radically resected gastric cancer. Methods: Genotyping for VEGF-A, VEGF-C and VEGFR-1,2,3 and for tumor integrins was carried out on pT3, peritoneal washing negative, radically resected gastric cancer patients recurring with either peritoneal-only or hematogenous metastases. Results: 101 patients were analyzed: 57 with peritoneal carcinomatosis only and 44 with hematogenous spread only. The following VEGF polymorphisms were associated with hematogenous metastases at the univariate analysis: the AA genotype of rs1570360 (VEGF-A) (p=0.0282), the AC genotype of rs699947 (VEGF-A) (p=0.006) and the GG genotype of rs7993418 (VEGFR-1) (p=0.0259). The following tumoral integrin polymorphisms were associated with hematogenous metastases at univariate analysis: the GG genotype of rs2269772 (ITGA3) (p=0.0002) and the GG genotype of rs11902171 (ITGV) (p=0.029). An increased rate of peritoneal carcinomatosis was found with the AA genotype of ITGA3 (p=0.014) and the CC genotype of ITGV (p=0.016). Variables with a statistically significant odds ratio for peritoneal carcinomatosis at the multivariate analyisis were diffuse tumoral histology (OR: 43,35, 95% CI: 9.07-207.9, p<0.0001) and the AA genotype of ITGA3 (OR: 5.69, 95% CI: 1.1-29.9, p=0.04). At the multivariate analysis the AC genotype of VEGF-A (OR: 8.08, 95% CI: 1.7-37.5, p=0.008) and intestinal histology (OR: 4.2, 95% CI: 1.8-9.9, p=0.0008) were independently associated with hematogenous metastases Conclusions: Tumor histology still represents a crucial factor for site of relapse. Furthermore a specific integrin polymorphism (AA genotype of ITGA3) and a specific VEGF-A polymorphism (AC genotype of VEGF-A) may represent a further asset in the definition of high-risk patients for respectively peritoneal carcinomatosis or hematogenous relapse.

Systemic treatment in breast-cancer patients with brain metastasis

Importance of the field: Breast cancer is the second most common cause of CNS metastasis, following lung cancer. With better control of systemic disease, the CNS is emerging as a sanctuary site of relapse in patients with otherwise controlled cancer.Areas covered in this review: Standard therapy for brain metastasis is currently whole-brain radiotherapy. Other treatment modalities include surgery and radiosurgery in selected cases, corticosteroids, and systemic chemotherapy. Little progress has been made in chemotherapy for the treatment of brain metastases, partly because tumors develop brain metastases at a stage when they become totally chemoresistant. Nevertheless, new treatment choices have emerged considering cytotoxic and biological agents for the treatment of CNS metastases in patients with breast cancer.What the readers will gain: In this review, we aimed to review current and future treatment options in the systemic treatment of brain metastases of breast cancer.Take home message: Corticosteroids, anti-epileptic drugs, and radiotherapy remain the cornerstones of management. The efficacy of conventional cytotoxic chemotherapeutics is limited. Novel biologic agents, lapatinib being the most promising, are currently investigated in the treatment of brain metastases of breast cancer with promising results.

Low incidence of brain metastasis as first site of relapse in patients with stage II and III non-small cell lung cancer

18051 Background: Lung cancer remains the leading cause of cancer mortality in both women and men in the United States. Despite recent advances in treatments, many patients with stage II and III non-small cell lung cancer (NSCLC) die of recurrent disease. Methods: A retrospective review was conducted to determine the incidence of brain metastasis as first site of relapse as well as other patterns of failure in patients with stage II and III NSCLC. From 1995 to 2003, 239 patients were identified from Minneapolis Veterans Affairs Medical Center tumor registry. Data was collected on the following variables to identify prognostic factors for brain metastasis and others patterns of failure: patient’s age, tumor histology, tumor size, nodal status, use of adjuvant chemotherapy, and type of adjuvant chemotherapy. Results: Of the 239 patients, only 12 (5%) had brain metastasis as first site of relapse. Median survival for patients with brain metastasis was 0.9 year (95% CI, 0.75–1.50). Out of 12 patients, 8 (67%) developed brain metastasis between 6 and 12 months after the initial diagnosis, 3 (25%) developed brain metastasis between 12 and 18 months and 1 (8%) developed brain metastasis as first site of relapse more than 18 months after initial diagnosis. Other patterns of failure were as follows: Thorax 36%, primary site 22%, primary + thorax 14% and distant metastasis 32%. Among 88 patients who underwent surgery as a part of definitive therapy, thorax was again the most common site of relapse (23%). Multivariate analysis showed that use of non-platinum based chemotherapy is a significant risk factor for relapse (p=0.02). Conclusion: Brain metastasis as first site of relapse is uncommon in patients with stage II and III NSCLC. Due to very low incidence of brain metastasis in this cohort of patients, prophylactic cranial radiation (which is the focus of few ongoing clinical trials) may cause more harm than good. No significant financial relationships to disclose.

Brain: The Common Site of Relapse in Patients with Pancoast or Superior Sulcus Tumors

Brain: The Common Site of Relapse in Patients with Pancoast or Superior Sulcus Tumors

Brain: The Common Site of Relapse in Patients with Pancoast or Superior Sulcus Tumors

We conducted a retrospective analysis to determine the occurrence of brain metastasis with superior sulcus tumors. We reviewed 685 charts of patients treated for upper lobe lung cancer between 1997 and 2003. Twenty-nine out of 685 patients (4%) had a diagnosis of Pancoast or superior sulcus tumor. The histology includes 11 patients with adenocarcinoma, seven with non-small cell lung cancer (NSCLC), six with squamous cell carcinoma, four with large cell carcinoma, and one with anaplastic carcinoma. Regarding stage at presentation: seven patients had stage IIB, two had stage IIIA, 16 had stage IIIB, and four had stage IV. The median follow-up is 14 months (range 6-70 months). The total occurrence of brain metastasis is seven out of 29 patients (24%). Two patients (stage IV) had brain metastasis at the time of presentation and five patients (stage IIB-III) developed brain metastasis at a median time of 10 months after the diagnosis. Stage associated with brain metastasis after diagnosis is two patients for stage IIB, two for stage IIIA, and one for stage IIIB. For the 25 patients with stage IIB to stage III disease, nine (36%) developed distant metastasis after definitive therapy. Out of these nine patients, five (55%) developed brain metastasis. It was the most common site of distant failure. Histology for seven patients with brain metastasis was four of seven with adenocarcinoma, two of seven with squamous cell carcinoma, and one of seven with NSCLC. Brain metatasis may be relatively common at diagnosis. The brain is the frequent site of failure for superior sulcus tumors. We recommend careful surveillance for brain metastasis during and after the therapy. We also recommend obtaining brain imaging prior to surgery in patients receiving induction therapy for the primary tumor.

Brain metastases as isolated site of relapse in patients with epithelial ovarian cancer previously treated with platinum and paclitaxel-based chemotherapy

Brain metastases in patients with epithelial ovarian cancer (EOC) have an estimated incidence of 0.3-1.9% and are isolated in up to 50% of these patients. The risk factors and the prognostic significance of isolated central nervous system (CNS) relapse in patients with EOC who received primary treatment with platinum and paclitaxel have not been identified. We conducted a retrospective study in patients with EOC who relapsed with isolated brain metastases and report our experience. Two hundred sixty-seven patients with stages III and IV EOC, in clinical complete remission after first-line treatment with platinum and paclitaxel, were included in our analysis. After a median follow-up of 65 months, 150 patients had relapsed. Eight patients (5%) had isolated brain metastases. Patient and disease characteristics did not differ among patients who relapsed with isolated brain metastases and those with relapse outside the CNS. Median time to first disease relapse, overall survival, and survival after relapse did not differ significantly between patients with brain metastases and those with relapse outside the CNS. Two patients have died 6 and 12 months after the diagnosis of brain metastases, and 5 patients are alive 4-35 months after the diagnosis of isolated brain metastases. Three patients remain free of disease 4-18 months after treatment with radiotherapy and systemic chemotherapy for their CNS metastatic disease. Patients with isolated brain metastases have comparable survival to patients with relapse outside the CNS, and long-term remission can be achieved in some cases, provided that systemic chemotherapy is added to local treatment.

Brain metastases as isolated site of relapse in patients with epithelial ovarian cancer previously treated with platinum and paclitaxel-based chemotherapy

Brain metastases in patients with epithelial ovarian cancer (EOC) have an estimated incidence of 0.3–1.9% and are isolated in up to 50% of these patients. The risk factors and the prognostic significance of isolated central nervous system (CNS) relapse in patients with EOC who received primary treatment with platinum and paclitaxel have not been identified. We conducted a retrospective study in patients with EOC who relapsed with isolated brain metastases and report our experience. Two hundred sixty-seven patients with stages III and IV EOC, in clinical complete remission after first-line treatment with platinum and paclitaxel, were included in our analysis. After a median follow-up of 65 months, 150 patients had relapsed. Eight patients (5%) had isolated brain metastases. Patient and disease characteristics did not differ among patients who relapsed with isolated brain metastases and those with relapse outside the CNS. Median time to first disease relapse, overall survival, and survival after relapse did not differ significantly between patients with brain metastases and those with relapse outside the CNS. Two patients have died 6 and 12 months after the diagnosis of brain metastases, and 5 patients are alive 4–35 months after the diagnosis of isolated brain metastases. Three patients remain free of disease 4–18 months after treatment with radiotherapy and systemic chemotherapy for their CNS metastatic disease. Patients with isolated brain metastases have comparable survival to patients with relapse outside the CNS, and long-term remission can be achieved in some cases, provided that systemic chemotherapy is added to local treatment.

Site of relapse after chemotherapy alone for stage I and II Hodgkin's disease

Background Short course chemotherapy followed by radiotherapy is a standard treatment for early Hodgkin's disease. There is yet no consensus regarding the appropriate radiotherapy portal following chemotherapy. A good guide to the adjuvant radiotherapy field is the site of relapse in patients treated with chemotherapy alone. Patients and methods From 1980 to 1996, 61 patients with stage I and II supradiaphragmatic Hodgkin's disease were treated with chemotherapy alone at the Royal Marsden Hospital. We undertook a retrospective review and failure analysis to define the pattern of recurrence. Results After a median follow-up of 6.5 years, 24 patients had relapsed giving a 5-year relapse rate of 40%. The 5 and 10-year actuarial survival rates were 94 and 89%, respectively with cause-sepecific survival being 94% at 5 and 10 years. Two-thirds of the relapses were nodal and supradiaphragmatic. Twenty patients (83%) relapsed in the initially involved sites of disease and this was the sole site of recurrence in 11 (45%) of patients. In retrospect, it appeared that at least 12 recurrences could have been prevented by involved field radiotherapy. Review of detailed imaging data (available in 9 out of 11 patients with recurrences in initial sites of disease) showed that the relapses were always in the initially involved nodes. Conclusion After chemotherapy alone in early stage HD most initial recurrences are nodal. Loco-regional recurrences are in the originally involved nodes. Based on limited data it appears that involved nodal RT is equivalent to involved field radiotherapy and may halve the risk of recurrence.

Local therapy and other factors influencing site of relapse in patients with localised Ewing's sarcoma

Relapse patterns have been documented in 191 children with localised Ewing's sarcoma treated with the United Kingdom Children's Cancer Group (UKCCSG) Ewing's Tumour regimen ET2. All received chemotherapy comprising ifosfamide, vincristine, doxorubicin and actinomycin D. Local treatment modality was excision and or radiotherapy depending on tumour site and response to primary chemotherapy. Although not strictly comparable, due to the clinical indications used for each modality, local relapse rates were very low and were similar, irrespective of the type of local treatment modality: radiotherapy (3/56), surgery (7/114) or a combination (0/20). Combined relapse (local + distant) rates were similarly low irrespective of the type of local therapy: radiotherapy (4/56), surgery (4/114) or a combination (0/20). Overall survival was lower in females ( P=<0.04), older children ( P=<0.002) and those with primaries at sites other than long bones ( P=<0.02). It is concluded that with effective intensive chemotherapy combined with either radiotherapy or surgery, local control in this study was excellent at sites other than the pelvis. Preventing distant relapse, predominantly to lung and bone, remains the major challenge.

High dose chemotherapy and stem cell rescue for aggressive non-Hodgkin's lymphoma: Pattern of failure and implications for involved-field radiotherapy

To evaluate the pattern of failure and outcome of patients with aggressive non-Hodgkin's lymphoma (NHL) undergoing high-dose chemotherapy (HDCT) and autologous stem cell rescue (SCR) with an emphasis on the role of adjuvant involved-field radiotherapy (IFRT). Fifty-three adult patients with aggressive NHL (46 intermediate-and 7 high-grade) underwent HDCT with SCR. All patients underwent induction chemotherapy prior to high dose intensification. Seven (13.2%) received IFRT to 10 disease sites either prior to or following HDCT. Indication included symptomatic or bulky disease, persistent disease, or to consolidate a complete response (CR). Sites of relapse were designated as old (involved prior to HDCT) or new (previously uninvolved). Median followup was 20.1 months (range, 1.2-69.3 months). The 4-year actuarial progression-free (PFS) and cause-specific (CSS) survivals of the entire group were 30.0 and 50.2%, respectively. Excluding toxic deaths, 24 patients (52.2%) relapsed. Sixteen (34.7%) failed in old and 15 (32.6%) in new sites. Patients treated with IFRT had a lower rate of relapse in old sites (0 vs. 41%) (p = 0.04) than patients treated with HDCT alone. Of the 141 sites present prior to induction, 127 (90.1%) were amenable to IFRT. Excluding irradiated sites, the overall 4-year local control (LC) of all amenable sites was 61.1%. Amenable sites failing to achieve a CR to induction had a poorer LC (32.0 vs. 95.1%) (p < 0.0001) than sites in CR. The 4-year LC of sites failing to achieve a CR to HDCT was 29.4%. Adjuvant IFRT improved the 4-year LC of all sites (100 vs. 61.1%) (p = 0.05), persistent sites following induction (100 vs. 32.0%) (p = 0.01) and persistent sites following HDCT (100 vs. 29.4%) (p = 0.01). Adjuvant IFRT was not associated with any untoward acute or late toxicity. The predominant site of relapse in patients with aggressive NHL undergoing HDCT and SCR is in sites of disease present prior to HDCT. However, the risk of relapse of prior disease sites varies greatly depending upon their response to chemotherapy. Sites at greatest risk are those failing to achieve a CR to induction regardless of their response to HDCT. IFRT is capable of reducing the high risk of relapse in these sites, the majority of which are amenable to IFRT. These results demonstrate a rationale for and possible benefit to IFRT in patients with aggressive NHL undergoing HDCT and SCR.

Sites of relapse in patients with neuroblastoma following bone marrow transplantation in relation to preparatory “debulking” treatments

Forty-one patients with high-risk neuroblastoma were treated between September 1977 and December 1987 at the Children's Hospital of Philadelphia with supralethal chemotherapy and total-body irradiation rescued by bone marrow transplantation. Twenty-six patients were treated following relapse and 15 were newly diagnosed. At the time of evaluation, January 1991, 11 of 41 patients (26.8%) remained in complete remission. Actuarial survival rates of patients transplanted following relapse were 0.35 and 0.31 at 2 and 5 years, respectively, and actuarial disease-free survival rates were 0.38 at 12 months and 0.27 at 24 months. The 2- and 5-year actuarial survival values for the patients with newly diagnosed disease were 0.53 and 0.25, respectively, and the 12-and 24-month disease-free survival rates were 0.47 and 0.27, respectively. There was no significant difference in survival between these groups. Twenty-nine of the 41 patients reviewed were available for analysis of the effect of local treatment. Thirteen had a combination of surgery and radiation (RT), 2 had surgery alone, 9 had RT alone, and in 5 patients no local treatment was given. The local relapse rate was 17%; it was 15% following surgery plus RT and 22% following RT alone. The failure rate combining local and distant relapse is 62% for surgery plus RT and 44% for RT alone. Although a local relapse rate of 17% is imperfect, it is a relatively small contribution to the overall relapse of 62%.

Is cranial radiation necessary for cns prophylaxis in pediatric NHL?

The records of 95 consecutive children ≤21 years of age with previously untreated diffuse histology NHL registered in our protocols from 1978 to 1983 were reviewed. Seventy-nine patients were considered eligible for analysis. The histologic subtypes represented included lymphoblastic (LB) 37%; histiocytic (DHL) 29%; undifferentiated (DU) 19%; poorly differentiated (DPDL) 9%; and unclassified (UNHL) 6%. Distribution of the patients according to stage showed Stage 1, 0%; Stage 11, 11%; Stage 111, 53%; Stage IV, 36%. Four different Memorial Hospital protocols for systemic chemotherapy were used (LSA2L2 73%; L10 9%; L1710%; L17M 8%); however, the IT (intrathecal) chemotherapy was uniform (Methotrexate: 6.0–6.25 mg/M 2 per treatment course) and was included in the induction, consolidation, and maintenance phases of all treatment protocols. Cranial radiation was not included in the CNS prophylaxis program. The overall median time of follow-up was 43 months. The overall CNS relapse rate was 6.3%, however, the incidence of CNS lymphoma presenting as the first isolated site of relapse in patients in otherwise complete remission (minimum follow-up of 19 months with 97% of patients off treatment) was only 1 58 (1.7%). Our data suggests that IT chemotherapy when given in combination with modern aggressive systemic combination chemotherapy, and without cranial radiation appears to be a highly effective modality for CNS prophylaxis regardless of stage, histology, or bone marrow or mediastinal involvement. Therefore, with the commonly used aggressive combination chemotherapy for the management of all stage diffuse pediatric NHL, and the known increased risk of leukoencephalopathy with combination of cranial radiation and intensive systemic and intrathecal chemotherapy, we believe that cranial radiation may not be indicated for CNS prophylaxis in pediatric NHL.

Social consequences of brain or liver relapse in small cell carcinoma of the bronchus

The time spent in hospital when cerebral metastases occur as the first site of relapse in patients with small cell carcinoma of the lung (SCCL) has been analysed and compared to the consequences of relapse in the liver. In the course of a clinical trial with 370 patients, 50 patients relapsed initially in the brain and 20 in the liver. The 2 groups were comparable with respect to performance status at diagnosis and the amount of home support available. Patients who relapsed in the brain suffered a greater deterioration in performance status, and spent a greater proportion of their remaining life in hospital than did patients whose initial relapse was in the liver. This difference was most marked in patients who died soon after relapse. Radiotherapy (20 Gy in 5 fractions over one week or 30 Gy in 10 fractions over 2 weeks) and dexamethasone were not very effective treatments for brain relapse though subjective responses were common. The substantial morbidity and lengthy hospitalisation resulting from brain relapse compared with relapse at another site is a important factor to be considered in assessing whether prophylactic cranial irradiation should routinely be offered to patients with SCCL.