Fabio Volterrani

Quadrantectomy versus lumpectomy for small size breast cancer

Between 1985 and 1987 quadrantectomy plus external radiotherapy and lumpectomy plus external and interstitial radiotherapy were compared in a randomized trial of patients with small carcinomas of the breast. Quadrantectomy involves excision of 2-3 cm of normal tissue around the tumour plus the removal of a sufficiently large portion of overlying skin and underlying fascia whilst lumpectomy removes only the tumour mass with a narrow margin of normal tissue. Patients in both groups also received total axillary dissection. 705 cases were evaluable, 360 quadrantectomies and 345 lumpectomies. No differences in distant metastases and survival were observed in the two groups. However, lumpectomy patients had a much higher frequency of local recurrences (7.0 vs. 2.2%). Since a local recurrence needs a second operation and creates severe psychological distress to the patient, conservative surgical procedures should include generous excision of normal tissue around the primary carcinoma plus intensive postoperative radiotherapy.

Short-term variation in labeling index as a predictor of radiotherapy response in human oral cavity carcinoma.

In vitro determination of [3H]thymidine labeling index (LI) was carried out on squamous cell carcinomas of the oral cavity from 52 patients before and during radiotherapy. Pretreatment LI values ranged from 0.01% to 50%. After administration of the first 10 Gy in five consecutive daily fractions, a decrease in LI was observed in 39 cases and an enhancement in 13 cases, with an overall median 70% decrease in the initial value. The type of variation induced by radiotherapy was not related to pretreatment LI except for tumors with a very low proliferative activity (LI less than or equal to 1.9%), which all showed a marked increase in LI. Pretreatment LI was not indicative of short- or long-term response to radiotherapy, whereas the variation induced on LI after 10 Gy was related to the clinical outcome. A variation in LI of more or less than 70% was not significantly associated (p = 0.077) with clinical objective response (respectively, 85 and 53%). However, all 8 patients who reached a complete regression, notwithstanding an enhancement or a slight decrease in LI, had a local recurrence within 19 months. Conversely, the probability of disease-free survival was 82% for the 11 patients whose tumors had a significant decrease in LI (greater than or equal to 70%) after the first 10 Gy.

Radiotherapy versus surgery in the treatment of cervix stage Ib cancer

In the years 1971-77 we have treated 250 Stage Ib patients with cancers of the cervix. One hundred twenty-three (49.2%) underwent a radical surgery, 37 had a classical Wertheim-Meigs operation, and 86 had a lymphadenectomy that was extended to the lumbar-aortic region. When feasible, all patients received postoperative radium therapy on the vaginal vault. The remaining 127 patients received a complete course of radiotherapy. This was not a randomized clinical trial. In fact surgery was preferred for patients who were younger (mean age: 49.6 years) and more physically fit, while radiotherapy was the treatment chosen for those who were older (mean age: 57.7) and generally less fit or obese. The 5 year NED survival was 89.3% in the surgical group and 90.9% in the radiotherapy group (P less than .05). Four fatal complications were observed in the surgical group (3.2%). Rate and causes of failures or complications are analyzed in detail.

Adjuvant Postoperative Radiotherapy in Locally Advanced Rectal and Rectosigmoidal Cancer

A pelvic recurrence is the cause of death in about 1/3 of radically operated patients for rectal and rectosigmoidal cancer without clinical evidence of distant metastases. Preoperative and postoperative radiotherapy are largely used to reduce the incidence of locoregional relapses and to improve disease-free and overall survival and quality of life. Benefits from radiotherapy have been widely demonstrated, and adjuvant postoperative radiotherapy is at present strongly recommended. Twenty-one patients with locally advanced (stage B2, B3, C) rectal (11 cases) and rectosigmoidal cancer (10 cases) were treated with postoperative radiotherapy at the National Cancer Institute of Milan from 1975 to 1978. The pelvis received a median dose of 4500 rad (range, 4000–5200 rad) in 5 to 7 weeks through AP, PA opposed fields; 6 patients received a boost of 1000 rad on the perineum. Median follow-up after surgery is 83 months (range, 24–63 months). Only 1 case (« 5%) had a pelvic recurrence, at the perineum. The expected recurrence rate after surgery alone is 40 %, and our favorable results after postoperative radiotherapy are comparable with recent data from other institutions. Radiotherapy side effects were moderate and transient; no late damages to small bowel were observed.

Cell kinetics in the study and treatment of head and neck cancer

Every cell able to reproduce itself passes through a cell cycle composed of four successive phases (Fig. 1), and each one is characterized by a series of biochemical events that prepare the following phase and that are governed by specific enzymes. The first one is the mitotic phase (M), which has been well known for a long time because it is morphologically identifiable under light microscopy. Another characteristic phase is that in which the cell synthesizes its DNA for replication (S). Between these phases two other time intervals are intercalated: a postmitotic (G1) and a premitotic (G2) phase, where G stands for gap. In fact, during these phases, RNA and proteins are synthesized, but biochemical events have not yet been well defined. In every tissue, either normal or neoplastic, the duration of the S phase, G2and M are quite constant, accounting respectively for 8–30 h, 1–2 h, and 30–90 min.

Failures (cause and time) of radiotherapy in oral cancer

The results of a retrospective clinical evaluation concerning 434 cases of oral carcinomas treated with radiotherapy from January 1959 to December 1967 are presented. The analysis of the results obtained shows that radiotherapy alone may offer a reasonable possibility of success in limited lesions (68.3% 5-year survival of Stage I patients). In more advanced local cases, and especially those with regional adenopathies, radiotherapy alone cannot consistently control the disease for a long period of time; 5-year survival from the onset of treatment was respectively 36.5% and 24.5% for Stage II and III cases. Moreover, if controlateral or bilateral metastatic adenopathies or fixed lymph nodes are present, the prognosis becomes dramatic (2.6% 5-year survival of Stage IV patients). Among the irradiation techniques currently available, curietherapy (interstitial applications or surface molds) presumably offers the best possibility of success, since the observed failures, both overall and stage by stage, are inferior. Radiotherapy alone may generally be of proven efficacy if the local or locoregional extension is limited. In more advanced cases a combined surgery-chemotherapy treatment method is recommended. The criteria for a combined therapeutic approach for these tumors are also discussed.

Ewing's sarcoma: an approach to radiological diagnosis.

All the pertinent radiographs of 83 patients with histologically proven Ewings sarcoma were reviewed. Forty-nine patients were in the pediatric age group, and 34 were adults. The mean age, the symptoms and time from symptoms to diagnosis were evaluated in the 2 groups. The site of primary involvement was in 54 % the long bones, 35 % the flat bones, 8 % the small bones and 3 % extraosseous. For the primary site we considered the diagnostic results of the standard radiographic investigations and in some cases the usefulness of angiography, xeroradiography and telethermography. At presentation we also evaluated the possible diffusion of the disease with standard radiographic surveys (chest and skeletal, including limbs) and with foot lymphography in selected cases. In this way, 57 patients (69 %) were considered to have localized disease. In this group, we also considered the value of the periodic radiographic follow-up, which enabled us to disclose the appearance of metastases (chest 64 %, bone 54 %, lymph nodes 11 %) in 28 cases (49 %). Finally, we made a comparison of the different radiologic and epidemiologic findings between children and adults.

Prognostic value of lymphography in cervical cancer.

This work is based on a review of 341 lymphographies carried out as a part of the initial diagnostic work-up performed on the same number of patients referred to our Institute for treatment from January 1961 to December 1976. As regards the distribution by clinical stage of the cases under consideration, there were 152 cases in Stage I (44.6%), 100 in Stage II (29.3%) and 89 in Stages III plus IV (26.1%). The positive lymphography incidence at the 2 extremes (Stage I a and Stages III plus IV) was 3.5 % and 46.0 %, respectively. The histologic type on its own did not seem to influence the incidence of lymph node metastases detectable by lymphography. For the negative cases, with all the stages mixed together, a 68.8 % 5-year survival rate free of disease was recorded, as compared with the 32.0 % found for the positive cases (P < 0.0001). A similar difference was recorded stage by stage. Our observations support the opinion that lymphography is valid in clinical practice to distinguish the minimum or nil lymph node invasion cases (negative) with favorable prognosis, from the cases having lymph node invasion of a certain importance or even at a maximum (positive), with a poor fate, independently of the initial clinical stage. Furthermore they suggest the advisability of reviewing the basic concepts of the clinical classification in cervical cancer, to be cautious in considering clinical reviews that do not report information of this importance, and to put under discussion different therapeutic approaches for cases presenting a lymphographic abnormality.

Present status of treatment for invasive cervical carcinoma.

The results are presented of a retrospective clinical study carried out on 341 patients affected with cancer of the uterine cervix, with lymphography in the pretreatment diagnostic work-up, treated in our Institute from January 1961 to December 1976. The clinical classification of the patients studied was: 157 cases in Stage I (46.0%), 95 cases in Stage II (27.9%), and 89 cases in Stages III and IV (26.1%). During the period considered, the therapeutic approach for carcinoma of the cervix was practically constant and in line with the therapeutic policy most frequently followed for these neoplasms. For the early stages (9/341 patients or 27.6%) preference was given to a radical surgery and postoperative radiotherapy combination; for borderline cases and « bulky » and « barrel-shaped » lesions, radiotherapy usually preceded surgical treatment to enlarge its indications and improve its results (36/341 patients or 10.5%). The cases that were more developed locally or that presented contraindications to surgery received radiological treatment alone (211/341 patients or 61.9%). Radiotherapy treatment consisted of radium therapy performed with a single application of 226Ra conventional sources, followed by percutaneous irradiation with 60Co-teletherapy in the more developed cases and/or in the presence of lymph node metastases. All the patients were submitted to diagnostic lymphography at the onset of the treatment and 92 (26.9%) had lymph node metastases. In the framework of this clinical review, the 5-year disease-free survival from onset of the treatment varied from 88.2% for the cases at Stage Ib occult, 72.5% for the cases at Stage Ib, 63.8% for the Stage II cases, to 40.5% for the cases at Stages III and IV. The presence of a pathologic report at lymphography makes a considerable difference in terms of disease-free, long-term survival after treatment.

Clinical results of lymphography in cancer of the uterine cervix. A retrospective study of 542 consecutive, unselected patients.

From 1961 to 1976, 542 patients were evaluated with foot lymphography for cancer of the cervix at the Istituto Nazionale Tumori of Milan. A group of 341 patients had lymphangiography as part of the initial diagnostic work-up. The overall incidence of positive examinations was 25% (9% stage I, 29% stage II, 46% stage III, 50% stage IV). In the 115 patients who had pelvic surgery the overall diagnostic accuracy of lymphography was 88%, with 2 false positive and 12 false negative reports. A second group of 90 patients was evaluated in the follow-up without clinical evidence of disease, and the incidence of metastases was 17%. Finally, a group of 111 patients was studied for recurrence, and in this group the incidence of metastases was 51%. As regards site of involvement, the external iliac chains were involved in 93 to 96% of the cases, the common iliac in 34 to 79%, and the para-aortic in 17 to 36% in the different clinical conditions. The highest incidence of para-aortic metastases was found in the clinically initial stages (I and II) and in the recurrences. The lymphographic involvement of the retroperitoneal nodes was usually limited to a single region (41%) or two regions (37%). Only in 22% of the positive cases was a diffuse involvement of the retroperitoneal node chains evident.