Early stage infradiaphragmatic Hodgkin's disease: results of radiotherapy and review of the literature.

PURPOSE: To assess the impact of modality therapy on long-term outcome for infradiaphragmatic Hodgkin's disease (IDHD). METHODS AND MATERIALS: During the period 1965-1997, 847 patients with early stage Hodgkin's disease (HD) were evaluated and treated at our institution, 20 of them had IDHD (2.4%). Patients characteristics: stage I, nine patients (five pathological stage (PS), and four clinical stage (CS)) and stage II: 11 patients (six PS and five CS). Two modalities of treatment were used: combined modality (CMT), consisting of chemotherapy followed by extended field radiotherapy or radiotherapy alone (XRT). All patients with CS or PS II, except in one case, were treated with CMT. Overall, 12 patients were treated with CMT and the remaining eight patients were treated with XRT. RESULTS: The relapse rate after initial treatment was 30%. Ten-year disease free survival (DFS) and 10-year cause-specific survival were 60% and 92%, respectively. There was a non-significant trend to a better DFS for the CMT group of patients (76% vs. 35% for the whole series and 100% vs. 24% for stage I patients). The four relapsed patients in the XRT group were inguino-femoral PS I. In four out of the six patients who relapsed (66%) the failure was located solely in the supradiaphragmatic area, outside of the radiation fields. CONCLUSIONS: In our experience, inguino-femoral stage I patients have a high relapse rate after XRT; consequently, CMT consisting of chemotherapy plus involved field radiotherapy should be recommended for early stage HD confined below diaphragm.     

Localised lymphoma of bone: prognostic factors and treatment recommendations. The Princess Margaret Hospital Lymphoma Group.

Twenty seven adult patients with newly diagnosed non-Hodgkin's lymphoma localised to either bone (Stage IE) or bone and regional lymph nodes (Stage IIE) were treated between 1967 and 1988. Median age was 53 years and the commonest histology (21 patients) was diffuse histiocytic lymphoma. Twenty-four patients were treated radically: 15 with radiation therapy (XRT) alone and nine with chemotherapy plus radiation therapy (CMT). The cause specific survival for these patients was 56% at 5 years and 40% at 10 years. Survival was significantly better for patients treated by CMT (88% at 5 years) as compared to XRT alone (40% at 5 years, P = 0.03) and for age less than 60 (72% at 5 years) compared to greater than or equal to 60 (30% at 5 years, P = 0.018). Relapse-free rate was 27% at 5 years with XRT alone and 89% with CMT (P = 0.01). Risk factors for loco-regional relapse (seven cases) included: large tumour bulk, treatment by XRT alone and use of 'limited' radiation fields. No radiation dose-response relationship could be identified in this study. Long term local control and survival for localised lymphoma of bone were excellent after treatment by CMT but XRT alone was associated with unacceptably high local and distant failure rates.     

Combined modality therapy for stage I-II large cell lymphoma

Between January 1978 and December 1986, 94 patients with Stage I-II large cell lymphoma were evaluated at Stanford University Medical Center and treated with a combination of chemotherapy (CTX) and irradiation (XRT). The predominant histology was diffuse large cell (78), followed by immunoblastic (7), follicular large cell (6), and diffuse mixed small and large cell lymphoma (3). Twenty-three patients had Stage I and 71 had Stage II disease. Fifty-one had extranodal involvement (13 IE, 38 IIE), and 11 had B symptoms (2 IB, 9 IIB). Lymphoma was supradiaphragmatic in 58 patients, infradiaphragmatic in 21, and only in extranodal sites in 15. Patients received either involved (81) or extended (13) field XRT with a median dose of 40 Gy and combination CTX with 2 to 9 cycles (median 6) of either CHOP (68), M-BACOD (8), C-MOPP (8), MACOP-B (4), or other (6). Seventy-two patients remain with no evidence of disease, 21 are dead with disease, and one suffered an intercurrent death. Among the 19 patients who relapsed, there were six failures within the XRT field only, two within and outside the XRT field, and 11 outside of the XRT fields only. Actuarial survival and freedom from relapse (FFR) for the entire population were 74% and 72% at 5-years, respectively (33 month median follow-up). Stage I patients achieved 81% survival and 78% FFR, and Stage II patients had 72% survival and 70% FFR. In univariate and multivariate analyses, a favorable outcome was associated with the CTX-XRT-CTX sequence of therapy (p = 0.001), low LDH (p = 0.01), and small tumor bulk (p = 0.04). There were no relapses or deaths among the 21 patients receiving the "sandwich" sequence (CTX-XRT-CTX) of therapy. This series may serve as a comparison with single modality treatment programs for localized large cell lymphoma using either XRT or CTX alone.     

Combined chemotherapy and radiation versus radiation alone in the management of localized angiocentric lymphoma of the head and neck.

BACKGROUND AND PURPOSE: To clarify the clinical benefit derived from the combined modality therapy (CMT) comprised of chemotherapy and involved-field radiotherapy (XRT) for stage I and II angiocentric lymphomas of the head and neck. MATERIAL AND METHODS: Of 143 patients with angiocentric lymphoma of the head and neck treated at the Yonsei Cancer Center between 1976 and 1995, 104 patients (XRT group) received involved-field XRT alone with a median dose of 50.4 Gy (range: 20-70 Gy), while 39 patients (CMT group) received a median three cycles (range: 1-6 cycles) of chemotherapy before starting involved-field XRT. The response rate, patterns of failure, complications, and survival data of the XRT group were compared with those of the CMT group. RESULTS: Despite a higher response rate, local failure was the most common pattern of failure in patients of the both groups. The patterns of failure, including the systemic relapse rate were not influenced by the addition of combination chemotherapy. Although both modalities were well tolerated by the majority of patients, aberrant immunologic disorders or medical illnesses, such as a hemophagocytic syndrome, sepsis, intractable hemorrhage, or the evolution of second primary malignancies were more frequently observed in patients of the CMT group. The prognosis of patients in the XRT group was relatively poor, with a 5-year overall actuarial survival rate of 38% and disease-free survival rate of 32%, respectively. However, their clinical outcome was not altered by the addition of systemic chemotherapy. Achieving complete remission was the most important prognostic factor on univariate and multivariate analyses, but treatment modality was not found to be a prognostic variable influencing survival. CONCLUSIONS: Involved-field XRT alone for angiocentric lymphoma of the head and neck was insufficient to achieve an improved survival rate, but the combination of chemotherapy and involved-field XRT failed to demonstrate any therapeutic advantage over involved-field XRT alone.     

Stage III Hodgkin's disease: improved survival with combined modality therapy as compared with radiation therapy alone

This is a retrospective analysis of 120 patients with pathologically stage IIIA and IIIB Hodgkin's disease treated from April 1969 to December 1982. The median follow-up was 108 months. Treatment consisted of radiation therapy (RT) alone in 54 patients and combined radiation therapy and MOPP (nitrogen mustard, vincristine, procarbazine, prednisone) chemotherapy (CMT) in 66 patients. Stage III patients treated with CMT have an improved actuarial 12-year survival as compared with patients treated with RT alone with MOPP reserved for relapse (80% v 64%; P = .026). The 12-year actuarial freedom from first relapse by treatment for stage III patients is 83% and 40%, respectively (P less than .0001). Improved survivals following combined modality therapy are seen for the following subgroups of stage III patients: stage III2, 66% (CMT) v 44% (total nodal irradiation; TNI), P = .04; stage III1, 97% (CMT) v 73% (TNI), P = .05; stage III mixed cellularity or lymphocyte depletion histology, 94% (CMT) v 65% (TNI), P = .007; and stage III extensive splenic involvement, 77% (CMT) v 58% (TNI), P = .02. These survival differences are not seen in patients with nodular sclerosis or lymphocyte predominance histology or in patients with minimal splenic involvement. These data indicate that the initial use of CMT in stage III Hodgkin's disease results in an improved survival as compared with initial treatment with RT with MOPP reserved for relapse. Patients with limited Stage IIIA disease may still be candidates for radiation therapy alone.     

Apoptosis and the Bcl-2 gene family -- patterns of expression and prognostic value in stage I and II follicular center lymphoma

PURPOSE: The prognostic significance of spontaneous levels of apoptosis and Bcl-2, Bax, and Bcl-x protein expression in follicular center lymphoma (FCL) is unknown. The objectives of this retrospective study were (1) to investigate the relationship between pretreatment apoptosis levels and long-term treatment outcome in patients with Stage I and II FCL; (2) to define the incidence and patterns of Bax and Bcl-x protein expression in human FC; and (3) to determine the relationship of Bcl-2, Bax, and Bcl-x expression with spontaneous apoptosis levels and clinical outcome in localized FCL. METHODS AND MATERIALS: Between 1974 and 1988, 144 patients with Stage I or II FCL were treated. Hematoxylin and eosin (H & E) stained tissue sections of pretreatment specimens were retrieved for 96 patients. Treatment consisted of regional radiation therapy (XRT) for 25 patients, combined modality therapy (CMT) consisting of combination chemotherapy and XRT for 57 patients, and other treatments for 14 patients. Median follow-up for living patients was nearly 12 years. The apoptotic index (AI) was calculated by dividing the number of apoptotic cells by the total number of cells counted and multiplying by 100. Expression of Bcl-2, Bax, and Bcl-x proteins was assessed using immunohistochemistry. RESULTS: The mean and median AI values for the entire group were 0.53 and 0.4, respectively (range: 0-5.2). The AI strongly correlated with cytologic grade, with mean AI values of 0.25 for grade 1, 0.56 for grade 2, and 0.84 for grade 3 (p < 0.0005; Kendall correlation). A positive correlation was present between grouped AI and grouped mitotic index (MI) (p = 0.014). For patients treated with CMT, an AI < 0.4 correlated with improved freedom from relapse (FFR) p = 0.0145) and overall survival (OS) (p = 0.0081). An AI < 0.4 did not correlate with clinical outcome for the entire cohort or for patients receiving XRT only. Staining of tumor follicles for the Bcl-2 protein was positive, variable, and negative in 73%, 15%, and 12% of cases, respectively. Positive staining of tumor follicles was observed in 96% of cases for both the Bax and Bcl-x proteins. Expression of Bcl-2, Bax, or Bcl-x did not correlate with AI or clinical outcome. CONCLUSION: The level of spontaneous apoptosis in pretreatment specimens correlates with cytologic grade of FCL and is a significant predictor of FFR and OS for patients with localized FCL receiving CMT.     

Localized extradural lymphoma: survival, relapse pattern and functional outcome. The Princess Margaret Hospital Lymphoma Group.

Between 1967 and 1988, 22 patients were treated at The Princess Margaret Hospital (PMH) for localized (stage IE) non-Hodgkin's lymphoma (NHL) presenting with spinal extradural compression. The median age of the patients was 55 years (range 18-76). Back pain (20 patients) and leg weakness (18 patients) were the commonest complaints at presentation. Seven patients (30%) were non-ambulatory (paraplegic or severely paretic) and four had imparied sphincter function. Diffuse histiocytic lymphoma (12 cases) was the commonest histology. All patients initially had laminectomy decompression and were referred to PMH post-operatively. One patient (with coincident metastatic carcinoma of the breast) was treated palliatively. The remaining 21 patients received radical post-operative treatment: radiation therapy (XRT) alone in 12 cases (25-45 Gy), radiation therapy plus systemic combination chemotherapy (combined modality therapy, CMT) in 9 cases. The overall actuarial survival for the radically treated patients was 55% at 10 years and there was a significant difference (p = 0.037) between those treated by XRT alone (33%) and those who received CMT (86%). Only one patient from each treatment group failed locally but the distant recurrence-free survival for the XRT group was 32% compared to 100% for the CMT group (p = 0.017). One patient developed primary central nervous system (CNS) relapse. The functional results of treatment were excellent: 19 of the 21 radically treated patients regained or retained normal ambulatory status and the remaining two patients had only minor disability. Decompressive surgery and radiotherapy for localized extradural lymphoma ensures a high rate of local control and functional recovery.(ABSTRACT TRUNCATED AT 250 WORDS)     

Radiation therapy alone or in combination with chemotherapy in the treatment of residual or inoperable carcinoma of the rectum and rectosigmoid or pelvic recurrence following colorectal surgery. Radiation Therapy Oncology Group study (76-16)

Between 1976 and 1981, 147 patients with residual, inoperable, or locally recurrent carcinoma of the rectum were randomized to receive either radiation (XRT) alone or XRT plus chemotherapy (concomitant 5-FU during XRT and maintenance 5-FU + MeCCNU). An initial field received 4,500-5,100 rad in 5-6 weeks, with a boost field dose to a maximum of 7000 rad/8 weeks (maximum 6,000 rad/7 weeks with chemotherapy), dependent on findings of special small bowel films. One hundred twenty-nine patients were evaluable (65 XRT, 64 XRT + chemo). There were no statistically significant differences between treatments with respect to overall survival, complete remission rate, time to disease progression, local failure rate, or radiation dose distribution. Median survival was 17 months for XRT, 18 months for XRT + chemo; the 2-year survival probability was 36% for XRT, 44% for XRT + chemo. Initial performance status was a significant prognostic factor for both survival and time to disease progression. A trend was observed favoring the combination treatment for patients with residual disease. Treatment complications were greater for the combined modality arm than for radiation alone. Twenty-seven patients (22%) were alive at last data analysis, with no evidence of disease (NED) from 2-51 months (30 months median). Patients with resection of gross disease before or after irradiation had a much better result than those with gross residual or without any resection, but the relative influence of patient selection versus impact of surgery remains unclear.     

Mediastinal masses in children with Hodgkin's disease. An analysis of the Children's Hospital of Philadelphia and the Hospital of the University of Pennsylvania experience.

From 1970 to 1988, 121 patients younger than 18 years of age who had newly diagnosed Hodgkin's disease were treated at the Children's Hospital of Philadelphia (CHOP) and the Hospital of the University of Pennsylvania (HUP), Philadelphia, Pennsylvania. Fifty-five of 79 children with mediastinal masses (MM) had pretreatment chest radiographs from which a mediastinal mass ratio (MMR) could be calculated. Within a range of MMR values, 0.25 was the best prognosticator for event-free survival (EFS) for all patients. In those treated with radiation therapy (RT) alone, the intrathoracic relapse rate was zero of five patients with small MM (MMR less than 0.25) versus five of eight patients with large MM (P = 0.09). For combined-modality therapy (CMT), there were intrathoracic relapses in zero of four patients with small MM versus 5 of 32 patients with large MM (P = 0.8). For CMT, the intrathoracic relapse rates for those receiving more than 3500 cGy versus less than 2500 cGy were 0 of 4 patients and 5 of 27 patients, respectively (P = 0.8). The intrathoracic relapse rate in children with large MM was significantly lower for CMT than for RT (5 of 32 patients versus 5 of 8 patients) (P = 0.02). The authors concluded that in pediatric Hodgkin's disease, a MM with a MMR greater than or equal to 0.25 may be associated with poor intrathoracic control after RT alone. Despite this, children with large MM treated with RT alone had an excellent overall survival rate.     

Hodgkin's disease limited to intrathoracic sites

The records of 1470 patients treated for Hodgkin's disease between 1960 and 1980 were reviewed, and sites of initial involvement were scored. Forty-four patients had disease limited to the chest after clinical and/or pathologic staging. Eighteen asymptomatic patients underwent a staging laparotomy and no occult subdiaphragmatic disease was identified. All 44 patients were treated with irradiation (XRT) to involved (IF), mantle (M), subtotal lymphoid (STLI), or total lymphoid (TLI) fields. Eighteen patients were also treated with chemotherapy, consisting of nitrogen mustard, vincristine, and procarbazine, with or without prednisone (MOP(P)), or procarbazine, melphalan, and vinblastine (PAVe). With a median follow-up of 7.5 years the survival at five and ten years was 93% and 89%, respectively, and the freedom from relapse (FFR) at five and ten years was 81% and 78%, respectively. Ten patients relapsed, all in supradiaphragmatic sites (including six relapses within lung parenchyma). Eight had initially received XRT alone, and two had received combined modality treatment. The risk of relapse in the 26 patients treated with XRT alone varied inversely with the volume irradiated: IF, 100% (3/3); M, 45% (3/7); STLI, 17% (2/12); TLI, 0% (0/4) relapsed. Seven of the eight relapsing patients treated with XRT alone were salvaged with subsequent XRT and/or chemotherapy whereas both of the combined modality patients who relapsed, died with progressive disease despite all salvage therapy.     

Stage IA and IIA supradiaphragmatic Hodgkin's disease: prognostic factors in surgically staged patients treated with mantle and paraaortic irradiation

A total of 315 pathologically staged (PS) patients with IA and IIA Hodgkin's disease (HD) were treated with mantle and paraaortic irradiation, and evaluated for freedom-from-first relapse (FFR), survival, prognostic factors, and long-term complications. The 14-year actuarial FFR and survival were 82% and 93%, respectively, with a median follow-up time of 9 years. Mediastinal size was the only factor that predicted for a lower FFR, P less than .001. Forty-nine patients have developed recurrent HD. Thirty-six patients are disease-free following retreatment and only 13 patients have died of HD. Patients with mixed cellularity (MC) histology were more likely to relapse below the diaphragm (11%) as compared with patients with nodular sclerosis (NS) (5.1%) or lymphocyte predominant (LP) (3.6%) histology. These relapses were often associated with bulky pelvic nodal adenopathy and salvage treatment with chemotherapy alone often failed to control recurrent disease. Alternative diagnostic and therapeutic recommendations are presented for these patients. Thyroid abnormalities represented the most common long-term complication with an actuarial risk at 16 years of 37%. Major complications were rare. Mantle and paraaortic irradiation is associated with a high FFR and a low risk of complications and should remain standard treatment for early-stage HD.     

Analysis of supradiaphragmatic clinical stage I and II Hodgkin's disease treated with radiation alone.

Patients with clinical Stage I and II Hodgkin's disease have been managed at the Princess Margaret Hospital for over 20 years, without the use of routine staging laparotomy. Our experience identified as adverse prognostic factors presence of a large mediastinal mass, B symptoms, and advanced age in presence of unfavorable histology (20). We had suggested previously that the use of extended field radiation therapy (XRT) was associated with a lower risk of relapse than involved field XRT or mantle XRT. There has been a trend over the past decade to select those patients with favorable prognostic factors for treatment with XRT alone and to use mantle plus upper abdominal XRT (extended field XRT) to treat them. A retrospective study of patients with clinical Stage I and II Hodgkin's disease treated at the Princess Margaret Hospital between 1978 and 1986 was conducted to determine the impact of patient selection and extended field radiation on outcome. The study involved 250 patients with supradiaphragmatic disease selected for treatment with radiation alone on the absence of adverse prognostic factors. Radiation techniques included involved field radiation in selected patients (those with upper neck involvement), mantle radiation in the earlier years, and mantle plus upper abdominal radiation in the later years of the study. Actuarial survival was 83.3% at 8 years; cause-specific survival was 90.1% and the relapse-free rate 71.6%. Local tumor control was 94.6%; only two patients had true infield failure. Multivariate analysis showed that significant prognostic factors included age, histology, and erythrocyte sedimentation rate. Extent of the radiation treatment volume was significant and influenced the risk of relapse, particularly out-of-field relapse, independently of other factors. A dose of 35 Gy was found to be sufficient for control of clinical disease. This study validated a previously developed model for the selection of clinically staged patients with Stage I and II Hodgkin's disease for treatment with radiation alone. Careful selection of these patients can yield excellent results without requiring that staging laparotomy be routinely performed or the use of systemic chemotherapy as the initial treatment.     

Ovarian cancer metastatic to the brain: What is the optimal management?

PURPOSE: To better define determinants of survival and optimal management strategies for patients with ovarian cancer and brain metastases. METHODS: A review of literature using Medline identified 15 case series of ovarian cancer patients with brain metastases (OBM). Each article was abstracted for survival data, and in all cases, the intervals between ovarian cancer diagnosis and brain metastasis identification, and between brain metastasis identification and last follow-up were recorded. Cases were categorized by patient characteristics and treatment modality for brain metastases. Estimated survival probabilities were plotted using the Kaplan-Meier method with differences between subgroups analyzed by the log-rank test. Cox proportional hazards model was used to identify independent prognostic factors age, number of metastasis, and treatment modality associated with survival. RESULTS: The median interval from ovarian cancer diagnosis to brain metastasis in 104 identified patients was 19.5 months. Brain metastasis was single in 43%, multiple in 41%, and not reported in 16% of cases. About 81.7% of patients were treated for their brain metastases using external radiation therapy (XRT), chemotherapy, and surgery. XRT was utilized in 76% of 104 patients and in 93% of treated patients. The most commonly used modalities were XRT alone (40%) and craniotomy and XRT (17%). The median survival (MS) for all patients regardless of treatment type was 6 months. Patients who received any treatment lived longer than those not receiving surgery/chemotherapy/XRT (MS; 7 months vs. 2 months, P = 0.0001). Patients with single brain metastasis had a longer median survival (21 months vs. 6 months, P = 0.049) when treated with craniotomy plus radiation and/or chemotherapy compared to treatment regimens that excluded craniotomy. In a multivariate analysis, only treatment type was significant in predicting survival. CONCLUSION: OBM portends a poor prognosis, however, long-term survival is possible. Patients appear to benefit from therapy, especially selected groups of OBM patients with single brain metastasis treated with radiation therapy and surgery.     

The impact of radiotherapy dose and other treatment-related and clinical factors on in-field control in stage I and II non-Hodgkin's lymphoma.

PURPOSE/OBJECTIVE: To assess local (in-field) disease control, identify potential prognostic factors, and elucidate the optimal radiotherapy dose in various clinical settings of Stage I and II non-Hodgkin's lymphoma (non-CNS). MATERIALS & METHODS: A total of 285 consecutive patients with Stage I and II non-Hodgkin's lymphoma were treated with curative intent, including 159 with radiotherapy (RT) alone and 126 with combined-modality therapy (CMT). Of these, 72 patients had low-grade lymphomas (LGL), 92 had intermediate or high-grade lymphomas (I/HGL), and 21 had unclassified lymphomas. Clinical and treatment variables with potential prognostic significance for in-field disease control, freedom from relapse (FFR), and absolute survival (AS) were evaluated by univariate and multivariate analyses. RESULTS: The 5-, 10-, and 20-year actuarial AS rates were 73%, 46%, and 33% for patients with LGL and 64%, 44%, and 18% for patients with I/HGL, respectively. The 5-, 10-, and 20-year actuarial FFR rates were 62%, 59%, and 49% for patients with LGL and 66%, 57%, and 57% for patients with I/HGL, respectively. Significant prognostic factors identified by the multivariate analysis were age, tumor size, and histology for AS; tumor size and treatment for FFR; and only tumor size for in-field disease control. There were 95 total failures, with only 12 occurring infield. Most failures (65%) were in contiguous unirradiated sites. All 4 in-field failures in patients with LGL occurred after RT doses < 30 Gy, although none occurred in 10 patients with small-volume LGL of the orbit treated with doses < 30 Gy. The 8 in-field failures in patients with I/HGL were distributed evenly throughout the RT dose range; 5 occurred in patients treated with CMT, all with tumors > 6 cm, and 4 with less than a complete response (CR) to chemotherapy. CONCLUSION: Our analysis suggests that the overwhelming problem in the treatment of non-Hodgkin's lymphoma is not in-field failure but, rather, failure in contiguous unirradiated sites. A dose of 20-25 Gy may be sufficient for small-volume LGL of the orbit. A dose of 30 Gy is sufficient for LGL in general, as well as for patients with nonbulky (< or = 6 cm) I/HGL treated with CMT who have a CR. However, patients with I/HGL treated with CMT for tumors > 6 cm and/or without a CR may benefit from doses > or = 40 Gy.     

Conformal therapy improves the therapeutic index of patients with anal canal cancer treated with combined chemotherapy and external beam radiotherapy

PURPOSE: To evaluate the clinical outcomes of three-dimensional conformal radiotherapy (3D-CRT) in patients with anal canal cancer, in terms of local control (LC), freedom from relapse (FFR), and overall survival (OS) rates, and to estimate long-term toxicity data. METHODS AND MATERIALS: Sixty historical patients, treated with conventional radiation techniques (C-RT), were used as controls, and 62 consecutive patients were treated with 3D-CRT. Patients treated with 3D-CRT received 54 Gy in 30 fractions delivered continuously, compared with 45-58.9 Gy (median dose, 54 Gy) in a split course in patients treated with C-RT. Chemotherapy consisted of 5-fluorouracil with either mitomycin-C or cis-platinum given concurrently with radiation. Survival curves were performed using the Kaplan-Meier model, and the Cox proportional hazards model was used for multivariate analysis of risk factors. RESULTS: No differences in stage and age distribution were observed between the two groups. Patients treated with 3D-CRT and C-RT had an actuarial 5-year LC rate of 85.1% and 61.1%, respectively (p = 0.0056); the FFR rate was 70.2% and 46.1% (p = 0.0166), and the OS rate was 80.7% and 53.9% (p = 0.0171). In multivariate analysis, factors of significance for LC were nodal (N) status (p < 0.001); for OS, 3D-CRT (p = 0.038), N status (p = 0.011), and T status (p = 0.012); and for FFR, 3D-CRT (p = 0.024) and N status (p < 0.001). CONCLUSION: The use of 3D-CRT allows patients with anal canal cancer to complete radiation and chemotherapy without interruption for toxicity, with significant improvements in LC, FFR, and OS.     

Prognostic factors in aggressive malignant lymphomas: description and validation of a prognostic index that could identify patients requiring a more intensive therapy. The Groupe d'Etudes des Lymphomes Agressifs.

The objectives of this study were to determine prognostic factors for response to treatment, freedom-from-relapse (FFR) survival, and overall survival of 737 aggressive malignant lymphoma patients treated with the doxorubicin, cyclophosphamide, vindesine, bleomycin, methylprednisolone, methotrexate with leucovorin, ifosfamide, etoposide, asparaginase, and cytarabine (LNH-84) regimen; to construct a prognostic index with factors isolated by multivariate analyses; and to validate this prognostic index with another set of patients. Complete response (CR) was reached in 75% of LNH-84 patients, and 30% of them relapsed. With a median follow-up of 36 months, median FFR survival and median overall survival were not reached. Low serum albumin level, high tumoral mass, weight loss, bone marrow involvement, greater than or equal to 2 extranodal sites, and increased lactic dehydrogenase (LDH) level were associated with a low response rate. Advanced stage, increased LDH level, and nonlarge-cell histologic subtypes (diffuse mixed, lymphoblastic, and small non-cleaved) were statistically associated with a high relapse rate and short FFR survival. Increased LDH level, low serum albumin level, tumoral mass larger than 10 cm, greater than or equal to 2 extranodal sites, advanced stage, and age older than 65 years were statistically associated with short overall survival. Four of these parameters, namely, LDH level, stage, number of extranodal sites, and tumoral mass, were put together to construct a prognostic index. This index partitioned LNH-84 patients into three subgroups of good, intermediate, and poor prognosis (P less than .00001): CR rates of 93%, 83%, and 61%; relapse rates of 12%, 25%, and 45%; 3-year FFR survival of 87%, 73%, and 53%, and 3-year survival of 88%, 71%, and 41%, respectively. This prognostic index was applied to a test set of patients: 155 patients treated on protocols of the Nebraska Lymphoma Study Group. Using this index, these patients had 3-year FFR survival of 70%, 40%, and 22% (P = .0002) and 3-year survival of 79%, 52%, and 31% (P = .005). In patients with aggressive lymphomas, this simple prognostic index could distinguish between patients requiring intensive treatment such as autologous bone marrow transplantation in first complete remission and those who could be treated with standard regimens.     

Radiation use and long-term survival in breast cancer patients with T1, T2 primary tumors and one to three positive axillary lymph nodes

BACKGROUND: For patients with Stage II breast cancer with one to three positive lymph nodes, controversy exists about whether radiation as a component of treatment provides a survival benefit. METHODS AND MATERIALS: We analyzed data from patients with Stage II breast cancer with one to three positive lymph nodes diagnosed from 1988-2002 in the Surveillance, Epidemiology, and End Results registry and compared the outcome of 12,693 patients treated with breast-conservation therapy with radiation (BCT + XRT) with the 18,902 patients treated with mastectomy without radiation (MRM w/o XRT). RESULTS: Patients treated with BCT + XRT were younger, were more likely to be treated in recent years of the study period, more commonly had T1 primary tumors, and had fewer involved nodes compared with those treated with MRM w/o XRT (p < 0.001 for all differences). The 15-year breast cancer-specific survival rate for the BCT + XRT group was 80% vs. 72% for the MRM w/o XRT group (p < 0.001). Cox regression analysis showed that MRM w/o XRT was associated with a hazard ratio for breast cancer death of 1.19 (p < 0.001) and for overall death of 1.25 (p < 0.001). The survival benefit in the BCT + XRT group was not limited to subgroups with high-risk disease features. CONCLUSIONS: Radiation use was independently associated with improved survival for patients with Stage II breast cancer with one to three positive lymph nodes. Because multivariate analyses of retrospective data cannot account for all potential biases, these data require confirmation in randomized clinical trials.     

Role of fast neutrons in the treatment of soft tissue sarcoma

The report deals with our data on evaluation of combined photon-neutron radiotherapy (CPNT) received by 33 patients with soft tissue sarcoma at the Clinic of the Urals Neutron Therapy Center. Follow-up ranged 10-80 months (median--68 months). Complete response was reported in 100% (control--45%). All the patients survived 12 months after treatment (control--85%); 5-year survival was 42 and 22%, respectively. Our modality appeared to be the only means of ionizing radiation dose dispensation in cases of early relapse after photon therapy when there was a glimmer of hope of stabilization.     

Clinical stage I and II Hodgkin's disease: Long-term results of therapy without laparotomy: Experience at one institution

Background: We concluded a program in which we administeredradiotherapy only to clinical stages I and II Hodgkin's diseasepatients at standard risk, with the addition of 4 cycles ofcombination chemotherapy before radiotherapy for high-risk patients. Patients and methods: From 1980 to 1991, 313 patients with clinicalstages I or II Hodgkin's disease underwent treatment in ourhospital. Fifty percent of the patients in groups previouslyidentified as being at high risk for relapse received 4 cyclesof combination chemotherapy before radiotherapy. The remaininghalf of the patients received radiotherapy only. Results: Low- and high-risk patients aged 15–59 yearshad, respectively, complete remission (CR) rates of 97% and94%, 5-year survivals of 95% and 91%, and 5-year freedom fromrelapse (FFR) rates of 78% and 89%. Older low- and high-riskgroups had CR rates of 97% and 93%, 5-year survivals of 60%and 56% and 5-year FFR of 77% and 93%, respectively. Conclusion: Here we present our favorable results after treatingstandard-risk patients with clinical stages I and II Hodgkin'sdisease with radiotherapy only. With the addition of chemotherapy,the rate of relapse in the high-risk patients was reduced belowthat of the standard-risk patients. Overall survival was thesame for the high- and standard-risk patients. adjuvant chemotherapy, Hodgkin's disease, radiotherapy, stages I and II