Can adjuvant pelvic radiation therapy after local excision or polypectomy for T1 and T2 rectal cancer offer an alternative option to radical surgery?

PURPOSE: To determine outcomes after adjuvant pelvic local radiation therapy (RT) +/- concurrent chemotherapy for T1 and T2 rectal carcinomas treated with local excision or polypectomy. METHODS: We retrospectively identified adult patients with histologically proven T1 and T2 rectal adenocarcinoma, diagnosed incidentally at time of local excision or polypectomy between 01 January 2007 and 31 December 2019, and appropriately staged to confirm N0 M0 status. Patients were excluded if they had recurrent cancer or had received total mesorectal excision (TME): anterior resection (AR) or abdominoperineal resection (APR). Patient, tumour and treatment factors, together with disease and toxicity outcomes were collected from institutional medical records, correspondence and investigation reports. Descriptive statistical analyses were employed. The primary endpoint was loco-regional control and secondary endpoints were treatment-related toxicity, disease free survival, overall survival and rate of surgical salvage for pelvic recurrence. RESULTS: The median age of the 15 eligible patients was 73 (range 49-82 years). There were 9 men (60%) and 6 women (40%). The majority had T1 disease (80%) and most had received endomucosal resection (80%). All patients received 43-52Gy (EQD2) to the primary and 43-48Gy (EQD2) to the pelvis with 46.6% receiving concurrent chemotherapy (infusional 5-FU or oral capecitabine). At median follow up of 51 months, there were no local or regional recurrences. One patient experienced an isolated distant relapse at 48 months without any locoregional recurrence. CONCLUSION: Our findings demonstrate good locoregional disease control with the use of adjuvant pelvic RT for T1 and T2 rectal adenocarcinoma initially treated with polypectomy or local (non-oncological) excision. These findings indicate that adjuvant pelvic RT may provide an alternative to TME surgery in patients with incidentally detected early rectal cancers.

Outcomes of young patients diagnosed with locally advanced rectal cancer.

BACKGROUND: The incidence of rectal cancer is higher in the older population. In developed nations, there has been a rise in incidence in young onset colorectal cancer (CRC). We examined the outcomes of locally advanced rectal cancer (LARC) in younger patients (yRC) compared with older patients, using a retrospective audit. METHODS: All cases of LARC referred to two tertiary referral cancer centres in Western Sydney were examined. Patient demographics, presenting symptoms, treatment, relapse free survival (RFS), overall survival (OS) and progression free survival (PFS) were obtained. Under 50 years old was used as the cut-off age for defining yRC. RESULTS: All 145 consecutive patients were treated for LARC, including 28 in the yRC and 117 in the older patient group. Median follow-up was 54 months. yRC were more likely to complete neoadjuvant therapy (100% vs. 86%; P=0.032) and to undergo more extensive surgical procedures (24% vs. 2%, P<0.0001). yRC were more likely to have microsatellite high (MSI) tumours (30% vs. 4.7%; P=0.003). yRC demonstrated significantly poorer RFS compared with the standard group (HR 2.79; median RFS 4.67 vs. 16.02 months; P=0.023). In the relapsed setting, yRC had poorer PFS compared with the standard group (median PFS 2.66 vs. 9.70, P=0.006, HR 3.04). A difference in OS was also seen between the two groups, with yRC demonstrating poorer OS (median OS 40.46 vs. 58.26 months, HR 3.48, P=0.036). CONCLUSIONS: Patients under 50 years with LARC are more likely to have MSI tumours with a more aggressive disease course and poorer RFS, PFS and OS. Initiatives to improve early detection of these patients may improve outcomes. Further research is necessary to understand this disease and optimise its treatment.

Examining the utility of lower dose radiotherapy for localised primary ocular adnexal MALT lymphoma.

INTRODUCTION: Most primary ocular adnexal lymphomas are those involving mucosa-associated lymphoid tissue (MALT). Radiotherapy (RT) dose regimens in the literature vary from the historically used high doses (up to 56 Gy) to lower dose RT. We aimed to examine our institution's experience with the use of orbital RT for treating early-stage primary ocular adnexal MALT lymphoma (POAML). METHODS: Patients treated for stage I or II POAML over a 12-year period (July 2006 to June 2018) were identified through institutional databases. Data were retrospectively collated through review of patient records. Descriptive statistical methods were employed to analyse the data. RESULTS: Eighteen patients (median age of 67; range 44-87yrs) with localised POAML (3 cases of bilateral disease) were identified, resulting in a total of 21 evaluable orbits. Eight (44%) patients were female, and all were documented to be of good performance status (ECOG 0-1). The median follow-up was 34 months (range 8-75 months). The commonest dose fractionation used was 20 Gy in 10 fractions (n = 13 orbits) and a 3D conformal or volumetric modulated arc therapy (VMAT) technique was used in the majority of cases. None of the patients experienced an in-field recurrence. One patient had experienced a contralateral orbital recurrence two years post-unilateral orbital RT for orbital MALT lymphoma. Three patients experienced distant relapse. CONCLUSION: The use of lower dose orbital RT such as 20 Gy in 10 fractions (or radio biologically equivalent) yields excellent local disease control in the management of ocular adnexal MALT lymphoma. The durability of the response appears to be favourable. Given the indolent nature of the disease and the low levels of toxicity associated with lower dose orbital RT, this regimen remains our favoured approach to the management of localised POAML.

Cut-point for Ki-67 proliferation index as a prognostic marker for glioblastoma.

INTRODUCTION: Ki-67 proliferation index (Ki-67 index) is used to quantify cell proliferation during histopathological assessment of various tumors including glioblastoma (GB). AIM: We aimed to assess correlation between Ki-67 index and overall survival in patients with GB and determine a cut-point for Ki-67 index that predicts for poorer survival. METHOD: Records of adult patients diagnosed with GB on histopathological specimens at a tertiary cancer center in Sydney between 1 January 2002 and 30 July 2012 were retrieved. Specimens of these patients were examined for quantification of Ki-67 staining by two independent pathologists. Patient, disease, treatment, and survival data were collected from hospital and cancer care service records. Statistical analysis was performed using proportional hazards models, Kaplan-Meier curves, and the minimum P-value approach. RESULT: Of the eligible 71 patients, 58% were males with median age of 58 (range 18-87). Seventy-three percent of patients were of ECOG performance status 0-1. There was a statistically significant correlation between Ki-67 index and overall survival. In patients with Ki-67 > 22% (n = 36), 5-year survival was approximately 30% compared to 5% in those with Ki-67 ≤ 22% (n = 35; log-rank P-value = 0.04; hazard ratio (HR) = 0.53; 95% confidence intervals (CI), 0.29-0.97). CONCLUSION: This study demonstrates a positive correlation between Ki-67 index and overall survival in patients with GB. Percentage staining of Ki-67 < 22% appears to predict for poorer survival in GB.

Randomized Trial of Systemic Therapy After Involved-Field Radiotherapy in Patients With Early-Stage Follicular Lymphoma: TROG 99.03.

PURPOSE: Follicular lymphoma (FL) is curable by involved-field radiotherapy (IFRT) in < 50% of patients with stage I to II disease. We hypothesized that adding systemic therapy to IFRT would improve long-term progression-free survival (PFS). PATIENTS AND METHODS: A multicenter randomized controlled trial enrolled patients with stage I to II low-grade FL after staging computed tomography scans and bone marrow biopsies. 18F-labeled fluorodeoxyglucose-positron emission tomography (PET) was not mandatory. Patients were randomly assigned to either arm A (30 Gy IFRT alone) or arm B (IFRT plus six cycles of cyclophosphamide, vincristine, and prednisolone [CVP]). From 2006, rituximab was added to arm B (R-CVP). RESULTS: Between 2000 and 2012, 150 patients were enrolled, 75 per arm. In arm B, 44 patients were allocated to receive CVP and 31 were allocated to receive R-CVP. At randomization, 75% had stage I, the median age was 57 years, 52% were male, and 48% were PET staged. With a median follow-up of 9.6 years (range, 3.1 to 15.8 years), PFS was superior in arm B (hazard ratio, 0.57; 95% CI, 0.34 to 0.95; P = .033). Ten-year PFS rates were 59% (95% CI, 46% to 74%) and 41% (95% CI, 30% to 57%) for arms B and A, respectively. Patients in arm B who received R-CVP had markedly superior PFS compared with contemporaneous patients in arm A (hazard ratio, 0.26; 95% CI, 0.07 to 0.97; P = .045). Fewer involved regions ( P = .047) and PET staging ( P = .056) were associated with better PFS. Histologic transformation occurred in four and 10 patients in arms B and A, respectively ( P = .1). Ten deaths occurred in arm A versus five in arm B, but overall survival was not significantly different ( P = .40; 87% and 95% at 10 years, respectively). CONCLUSION: Systemic therapy with R-CVP after IFRT reduced relapse outside radiation fields and significantly improved PFS. IFRT followed by immunochemotherapy is more effective than IFRT in early-stage FL.

Clinical features, management and prognosis of multifocal primary bone lymphoma: a retrospective study of the international extranodal lymphoma study group (the IELSG 14 study).

'Multifocal bone lymphoma' or 'polyostotic lymphoma' is a neoplasm with exclusive multifocal involvement of the skeleton, without affecting lymph nodes or other soft tissues. Knowledge on this uncommon condition is limited because the related literature is sparse and fragmentary. We reviewed cases of multifocal bone diffuse large B-cell lymphoma (MB-DLBCL) registered in a clinico-pathological database of the International Extranodal Lymphoma Study Group that includes 499 cases of bone lymphoma. Clinical features, management and prognosis of 37 MB-DLBCL patients and 63 'controls' (stage-IV DLBCL and skeletal involvement) were analysed. Presentation and treatment of MB-DLBCL and controls were identical. At a median follow-up of 52 months (10-189), MB-DLBCL patients exhibited a significantly better response rate (92% vs. 65%; P = 0·002), progression-free survival (5-year: 56 ± 9% vs. 34 ± 6%; P = 0·003) and overall survival (5-year: 74 ± 8% vs. 36 ± 7%; P = 0·002). Among MB-DLBCL patients, the use of post-chemo radiotherapy was associated with better overall survival (5-year: 83 ± 12% vs. 55 ± 16%; P = 0·003). Two MB-DLBCL patients (5·4%) with spine and skull involvement experienced central nervous system (CNS) relapse. Thus, MB-DLBCL patients exhibit a significantly better prognosis compared to patients with advanced-stage DLBCL, and should be treated with conventional anthracycline-based chemotherapy, keeping intensified treatment for relapsing cases, considering involved-field radiotherapy, and CNS prophylaxis in high-risk patients.

The clinical features, management and prognosis of primary and secondary indolent lymphoma of the bone: a retrospective study of the International Extranodal Lymphoma Study Group (IELSG #14 study).

Indolent lymphomas primarily involving the skeleton (iPBL) represent < 1% of all primary bone lymphomas. The management and prognosis have not been previously described. Patients with primary and secondary iPBL were selected from an international database of 499 patients with a histopathological diagnosis of non-Hodgkin lymphoma and skeleton involvement, and clinical features, management and prognosis were analyzed. Twenty-six (5%) patients had an iPBL. Ten patients had small lymphocytic lymphoma, 10 had follicular lymphoma and six had lymphoplasmacytic lymphoma. Eleven patients had limited stage and 15 had advanced disease. The overall response rate was 73% (95% confidence interval [CI] = 57-89%). Median follow-up was 58 months, and the 5- and 10-year progression-free survival (PFS) rates were 37 ± 10% and 25 ± 12%, respectively. Nine patients are alive, with 5- and 10-year overall survival (OS) rates of 46 ± 10% and 29 ± 11%, respectively. Patients with small lymphocytic lymphoma showed significantly better outcome than patients with follicular lymphoma. Performance status and stage of disease were independently associated with OS. The prognosis of patients with primary bone lymphoplasmacytic or follicular lymphoma was less favorable.